Biochemistry - First Aid

Question 1

Chromatin Structure

Answer 1

Question 2

DNA exists in the condensed _____ form to fit into the nucleus.

Answer 2

chromatin

Question 3

DNA loops twice around a _____ to form a _____ (“beads on a string”).

Answer 3

histone octamer

nucleosome

Question 4

H1 binds to the _____ and to the _____, thereby stabilizing the _____.

Answer 4

nucleosome

linker DNA

chromatin fiber

Question 5

_____ groups give DNA a (-) charge.

Answer 5

Phosphate

Question 6

_____ give histones a (+) charge.

Answer 6

Lysine

Arginine

Question 7

In _____, DNA condenses to form _____.

Answer 7

mitosis

chromosomes

Question 8

DNA and histone synthesis occurs during the _____.

Answer 8

S phase

Question 9

Mitochondria have their own DNA which is _____ and does not utilize _____.

Answer 9

circular

histones

Question 10

Chromatin:

• condensed
• darker on EM
• transcriptionally inactive
• sterically inaccessible
• ↑ methylation
• ↓ acetylation

Answer 10

heterochromatin

Hetero-Chromatin = Highly Condensed

Question 11

_____ are inactive X chromosomes which may be visible on the periphery of the nucleus.

Answer 11

Barr bodies

*heterochromatin

Question 12

Chromatin:

• less condensed
• lighter on EM
• transcriptionally active
• sterically inaccessible

Answer 12

euchromatin

Euchromatin = Expressed

Question 13

_____ changes the expression of a DNA segment without changing the sequence.

Answer 13

DNA Methylation

Question 14

_____ is involved with genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging and carcinogenesis.

Answer 14

DNA Methylation

Question 15

Methylation within _____ typically represses gene transcription.

Answer 15

gene promoter (CpG islands)

CpG Methylation Makes DNA Mute

Question 16

_____ usually causes reversible transcriptional suppression, but can also cause activation depending on location of methyl groups.

Answer 16

Histone Methylation

Histone Methylation Mostly Makes DNA Mute

Question 17

_____ relaxes DNA coiling, allowing for transcription.

Answer 17

Histone Acetylation

Histone Acetylation makes DNA Active

Question 18

Purine

Answer 18

Question 19

Pyrimidine

Answer 19

Question 20

Nucleoside Composition

Answer 20

NucleoSide = base + (deoxy)ribose (Sugar)

Question 21

Nucleotide Composition

Answer 21

NucleoTide = base + (deoxy)ribose + phosphaTe

*linked by 3’-5’ phosphodiester bond

Question 22

5’ end of incoming nucleotide bears the _____.

Answer 22

triphosphate

*energy source for the bond

Question 23

Triphosphate bond is the target of _____ attack.

Answer 23

3’ hydroxyl

Question 24

Purines

Answer 24

A, G - 2 rings

PURe As Gold

Question 25

Pyrimidines

Answer 25

C, U, T - 1 ring

CUT the PY (pie)

Question 26

Deamination of cytosine forms _____.

Answer 26

uracil

Question 27

Deamination of adenine forms _____.

Answer 27

hypoxanthine

Question 28

Deamination of guanine forms _____.

Answer 28

xanthine

Question 29

Deamination of 5-methylcytosine forms _____.

Answer 29

thymine

Question 30

Uracil is found in _____.

Answer 30

RNA

Question 31

Thymine is found in _____.

Answer 31

DNA

Question 32

Methylation of uracil makes _____.

Answer 32

thymine

THYmine has meTHYl

Question 33

G-C bonds have _____ H bonds.

Answer 33

3

Question 34

A-T bonds have _____ H bonds.

Answer 34

2

Question 35

Higher G-C bonds means _____ of DNA.

Answer 35

higher melting T

C-G bonds are like Crazy Glue

Question 36

Amino Acids Essential for Purine Synthesis

Answer 36

Glycine

Aspartate

Glutamine

Cats Purr until they GAG

Question 37

De novo Pyrimidine and Purine Synthesis

Answer 37

Question 38

Pyrimidine Synthesis Blockers:

inhibits dihydroorotate dehydrogenase

Answer 38

Leflunomide

Question 39

Pyrimidine Synthesis Blockers:

inhibits dihydrofolate reductase (↓ deoxythymidine monophosphate [dTMP])

Answer 39

Methotrexate (MTX) - humans

Trimethoprim (TMP) - bacteria

Pyrimethamine - protozoa

Question 40

Pyrimidine Synthesis Blockers:

inhibits thymidylate synthase (↓ dTMP)

Answer 40

5-fluorouracil (5-FU)

5-FU + capecitabine = 5-F-dUMP

Question 41

Purine Synthesis Blockers:

inhibit de novo purine synthesis

Answer 41

6-mercaptopurine (6-MP)

*Azathioprine - prodrug

Question 42

Purine Synthesis Blockers:

inhibit inosine monophosphate dehydrogenase

Answer 42

Mycophenolate

Ribavirin

Question 43

Purine and Pyrimidine Synthesis Blockers:

inhibits ribonucleotide reductase

Answer 43

Hydroxyurea

Question 44

Carbamoyl Phosphate Synthase I is found in the _____.

Answer 44

Mitochondria

CPS1 = m1tochondria (urea cycle)

Question 45

Carbamoyl Phosphate Synthase II is found in the _____.

Answer 45

Cytosol

CPS2 = cyTWOsol

Question 46

Purine Salvage Deficiencies

Answer 46

Question 47

_____ is required for degradation of adenosine and deoxyadenosine.

Answer 47

Adenosine Deaminase (ADA)

Question 48

In ADA deficiency, ↓ dATP → _____.

Answer 48

lymphotoxicity

Question 49

Adenosine Deaminase Deficiency is one of the major causes of _____.

Answer 49

autosomal recessive SCID

Question 50

_____ is caused by defective purine salvage due to absent HGPRT, which converts hypoxanthine to IMP and guanine to GMP.

Answer 50

Lesch-Nyhan Syndrome

Question 51

_____ results in excess uric acid production and de novo purine synthesis.

Answer 51

Lesch-Nyhan Syndrome

Question 52

Lesch-Nyhan Syndrome is an _____ disease.

Answer 52

X-linked recessive

Question 53

Lesch-Nyhan Syndrome Findings

Answer 53

HGPRT

• Hyperuricemia
• Gout
• Pissed off (aggression, self-mutilation)
• Retardation (intellectual disability)
• DysTonia

Question 54

Lesch-Nyhan Syndrome Treatment

Answer 54

Allopurinol

Febuxostat

Question 55

Genetic Code Features

Answer 55

• Unambiguous
• Degenerate/Redundant
• Commaless, Non-Overlapping
• Universal

Question 56

Genetic Code Features:

each codon specifies only 1 amino acid

Answer 56

Unambiguous

Question 57

Genetic Code Features:

most amino acids are coded by multiple codons

Answer 57

Degenerate/Redundant

Question 58

Codons that differ in the 3rd (_____) position may code for the same tRNA/amino acid.

Answer 58

wobble

Question 59

Specific base pairing is usually required only in the _____ of the mRNA codon.

Answer 59

first 2 nucleotide positions

Question 60

_____ are encoded by only 1 codon.

Answer 60

Methionine (AUG)

Tryptophan (UGG)

Question 61

Genetic Code Features:

read from a fixed starting point as a continuous sequence of bases

Answer 61

Commaless, Non-Overlapping

Question 62

Genetic Code Features:

genetic code is conserved throughout evolution

Answer 62

Universal

Question 63

DNA Replication

Answer 63

Question 64

In both prokaryotes and eukaryote, DNA replication is _____ and involves both _____ synthesis and occurs in the _____ direction.

Answer 64

• semiconservative
• continuous and discontinuous (Okazaki fragments)
• 5’ → 3’

Question 65

_____ is the particular consensus sequence of base pairs in genome where DNA replication begins.

Answer 65

Origin of Replication

*prokaryotes - single

*eukaryotes - multiple

Question 66

_____ sequences are found in promoters and origins of replication.

Answer 66

AT-rich sequences

*TATA box

Question 67

The _____ is a Y-shaped region along the DNA template where leading and lagging straands are synthesized.

Answer 67

Replication Fork

Question 68

_____ unwinds the DNA template at the replication fork.

Answer 68

Helicase

Helicase Halves DNA

Question 69

_____ prevents DNA strands from reannealing.

Answer 69

Single-Stranded Binding Proteins

Question 70

_____ create a single- or double-stranded break in the helix to add or remove supercoils.

Answer 70

DNA Topoisomerases (TOP)

Question 71

In eukaryotes, _____ inhibit TOP I.

Answer 71

Irinotecan

Topotecan

Question 72

In eukaryotes, _____ inhibit TOP II.

Answer 72

Etoposide

Teniposide

Question 73

In prokaryotes, _____ inhibit TOP II (DNA Gyrase) and TOP IV.

Answer 73

Fluoroquinolones

Question 74

_____ makes an RNA primer on which DNA Polymerase III can initiate replication.

Answer 74

Primase

Question 75

_____ elongates the leading strand by adding deoxynucleotides to the 3’ end.

Answer 75

DNA Polymerase III

*only in prokaryotes

Question 76

_____ elongates the lagging strand until it reaches the primer of the preceding fragment.

Answer 76

DNA Polymerase III

*only in prokaryotes

Question 77

DNA Polymerase III has _____ synthesis.

Answer 77

5’ → 3’

Question 78

DNA Polymerase III proofreads with _____ exonuclease.

Answer 78

3’ → 5’

Question 79

Drugs blocking DNA replication often have a _____ thereby preventing addition of the next nucleotide (“chain termination”).

Answer 79

modified 3’ OH

Question 80

_____ degrades the RNA primer and replaces it with DNA.

Answer 80

DNA Polymerase I

*only in prokaryotes

Question 81

DNA Polymerase I excises the RNA primer with _____.

Answer 81

5’ → 3’ exonuclease

Question 82

_____ catalyzes the formation of a phosphodiester bond within a strand of double-stranded DNA.

Answer 82

DNA Ligase

Ligase Links DNA

Question 83

_____ joins the Okazaki fragments.

Answer 83

DNA Ligase

Ligase Links DNA

Question 84

_____ is a reverse transcriptase (RNA-dependent DNA Polymerase) that adds DNA (TTAGGG) to 3’ ends of chromosomes to avoid loss of genetic material with every duplication.

Answer 84

Telomerase

Telomerase TAGs for Greatness and Glory

*only in eukaryotes

Question 85

_____ is often dysregulated in cancer cells, allowing unlimited replication.

Answer 85

Telomerase

Question 86

Severity of DNA Mutations

Answer 86

silent << missense < nonsense < frameshift

Question 87

Purine → Purine or Pyrimidine → Pyrimidine Mutation

Answer 87

Transition

Question 88

Purine ⇆ Pyrimidine Mutation

Answer 88

Transversion

Question 89

DNA Mutations:

nucleotide substitution but codes for same (synonymous) amino acid, often base in 3rd position of codon (tRNA wobble)

Answer 89

Silent

Question 90

DNA Mutations:

nucleotide substitution resulting in changes amino acid (conservative if new amino acid is similar in chemical structure)

Answer 90

Missense

Question 91

Sickle Cell Disease is caused by the _____.

Answer 91

substitution of glutamic acid with valine

*missense

Question 92

DNA Mutations:

nucleotide substitution resulting in early stop codon (UAA, UAG, UGA), usually results in nonfunctional protein

Answer 92

Nonsense

Stop the Nonsense!

Question 93

DNA Mutations:

deletion or insertion of a number of nucleotides not divisible by 3, resulting in misreading of all nucleotides downstream

Answer 93

Frameshift

Question 94

Duchenne Muscular Dystrophy and Tay-Sachs Disease is caused by _____ mutation.

Answer 94

Frameshift

Question 95

Mutation at a _____ → retained intron in the mRNA → protein with impaired or altered function

Answer 95

splice site

Question 96

Lac Operon Mechanism

Answer 96

Question 97

Lac Operon and Glucose

Answer 97

Question 98

Glucose is the preferred metabolic substrate in E. coli, but when glucose is absent and lactose is available, the _____ is activated to switch to lactose metabolism.

Answer 98

Lac Operon

Question 99

Lac Operon Mechanism:

Low Glucose

Answer 99

↓ glucose → ↑ adenylate cyclase activity → ↑ generation of cAMP from ATP → activation of catabolite activator protein (CAP) → ↑ transcription

Question 100

Lac Operon Mechanism:

High Glucose

Answer 100

↑ glucose → unbinds repressor protein from repressor/operator site → ↑ transcription

Question 101

Single Strand DNA Repair:

specific endonucleases release the oligonucleotides containing damaged bases, DNA polymerase and ligase fill and reseal the gap

Answer 101

Nucleotide Excision Repair

Question 102

Single Strand DNA Repair:

repairs bulky helix-distorting lesions

Answer 102

Nucleotide Excision Repair

Question 103

Single Strand DNA Repair:

occurs in G1 phase of the cell cycle

Answer 103

Nucleotide Excision Repair

Question 104

Single Strand DNA Repair:

defective in xeroderma pigmentosum (inability to repair DNA pyrimidine dimers cause by UV exposure) which causes dry skin, extreme light sensitivity and skin cancer

Answer 104

Nucleotide Excision Repair

Question 105

Single Strand DNA Repair:

base-specific Glycosylase removes altered base and creates AP site (apurinic/apyramidinic), one or more nucleotides are removed by AP-Endonuclease which cleaves the 5’ end, Lyase cleaves the 3’ end, DNA Polymerase-β fills the gap and DNA Ligase seals it

Answer 105

Base Excision Repair

GEL PLease

Question 106

Single Strand DNA Repair:

occurs throughout the cell cycle

Answer 106

Base Excision Repair

Question 107

Single Strand DNA Repair:

important in the repair of spontaneous/toxic deamination

Answer 107

Base Excision Repair

Question 108

Single Strand DNA Repair:

newly synthesized strand is recognized, mismatched nucleotides are removed and the gap is filled and resealed

Answer 108

Mismatch Repair

Question 109

Single Strand DNA Repair:

occurs predominantly in the S phase of the cell cycle

Answer 109

Mismatch Repair

Question 110

Single Strand DNA Repair:

defective in Lynch Syndrome (hereditary nonpolyposis colorectal cancer [HNPCC])

Answer 110

Mismatch Repair

Question 111

Double Strand DNA Repair:

brings together 2 ends of DNA fragments to repair double-stranded breaks, no requirement for homology, some DNA may be lost

Answer 111

Nonhomologous End Joining

Question 112

Double Strand DNA Repair:

defective in Ataxia Telangiectasia and Fanconi Anemia

Answer 112

Nonhomologous End Joining

Question 113

Double Strand DNA Repair:

requires 2 homologous DNA duplexes, a strand from the damaged dsDNA is repaired using a complementary strand from the intact homologous dsDNA as a template, restores duplexes accurately without loss of nucleotides

Answer 113

Homologous Recombination

Question 114

Double Strand DNA Repair:

defective in breast/ovarian cancers with BRCA1 mutation

Answer 114

Homologous Recombination

Question 115

mRNA Start Codon

Answer 115

AUG

*methionine - eukaryotes

*N-formylmethionine (fMet) - prokaryotes

Question 116

mRNA Stop Codons

Answer 116

UAA, UAG, UGA

Question 117

Functional Organization of a Eukaryotic Gene

Answer 117

Question 118

The _____ is the site where RNA Polymerase II and other transcriptions factors bind to DNA upstream from gene locus (AT-rich upstream sequence with TATA and CAAT boxes).

Answer 118

Promoter

Question 119

_____ mutation commonly results in dramatic ↓ in level of gene transcription.

Answer 119

Promoter

Question 120

The _____ is the DNA locus where regulatory proteins (“activators”) bind → increasing expression of a gene on the same chromosome.

Answer 120

Enhancer

Question 121

The _____ is the DNA locus where regulatory proteins (“repressors”) bind → decreasing expression of a gene on the same chromosome.

Answer 121

Silencers

Question 122

In eukaryotes, RNA Polymerase I makes _____, present only in the nucleolus.

Answer 122

rRNA

r = rampant

* most common

Question 123

In eukaryotes, RNA Polymerase II makes _____, which is read 5’ → 3’.

Answer 123

mRNA

m = massive

*largest

Question 124

In eukaryotes, RNA Polymerase III makes _____.

Answer 124

tRNA

t = tiny

*smallest

Question 125

_____ opens DNA at the promoter site.

Answer 125

RNA Polymerase II

Question 126

_____ found in _____ inhibits RNA Polymerase II and causes severe hepatotoxicity if ingested.

Answer 126

α-amanitin

Amanita phalloides (death cap mushrooms)

Question 127

_____ inhibits RNA Polymerase in both prokaryotes and eukaryotes.

Answer 127

Actinomycin D

Question 128

In prokaryotes, _____ (multisubunit complex) makes all 3 kinds of RNA.

Answer 128

1 RNA Polymerase

Question 129

_____ inhibits DNA-dependent RNA Polymerase in prokaryotes.

Answer 129

Rifampin

Question 130

RNA Processing in Eukaryotes

Answer 130

Question 131

_____, the initial transcript in eukaryote RNA processing, is modified and becomes mRNA.

Answer 131

heterogenous nuclear RNA (hnRNA)

Question 132

RNA Processing

Answer 132

1. capping of 5’ end (addition of 7-methylguaanosine cap)
2. polyadenylation of 3’ end (~ 200 A’s)
3. splicing out of introns

Question 133

Capped, tailed and spliced transcript is called _____.

Answer 133

mRNA

Question 134

_____ is transported out of the nucleus into the cytosol, where it is translated.

Answer 134

mRNA

Question 135

mRNA quality control occurs at _____, which contain exonucleases, decapping enzymes, and microRNAs.

Answer 135

cytoplasmic processing bodies (P-bodies)

Question 136

mRNAs may be degraded or stored in _____ for future translation.

Answer 136

cytoplasmic processing bodies (P-bodies)

Question 137

_____ Polymerase does not require a template.

Answer 137

Poly-A

Question 138

Polyadenylation Signal

Answer 138

AAUAAA

Question 139

Splicing of Pre-mRNA

Answer 139

Question 140

_____ contain the actual genetic information coding for protein.

Answer 140

Exons

Exons Exit and are Expressed.

Question 141

_____ are intervening noncoding segments of DNA.

Answer 141

Introns

Introns Intervene In the nucleus.

Question 142

_____ can produce a variety of products from a single hnRNA sequence.

Answer 142

Alternative Splicing

Question 143

Alternative Splicing

Answer 143

Question 144

_____ are small, conserved, noncoding RNA molecules that posttranscriptionally regulate gene expression by targeting the 3’ untranslated region of specific mRNAs for degradation or translational repression.

Answer 144

MicroRNAs (miRNAs)

Question 145

_____ has 75-90 nucleotides, 2° structure, cloverleaf form, and anticodon end is opposite 3’ aminoacyl end.

Answer 145

tRNA

Question 146

All tRNAs have _____ at the 3’ end with a high percentage of chemically modified bases.

Answer 146

CCA

Can Carry Amino acids

Question 147

The amino acid is covalently bound to the _____ of the tRNA.

Answer 147

3’ end

Question 148

The _____ of the tRNA contains the TΨC (ribothymidine, pseudouridine, cytidine) sequence necessary for tRNA-ribosome binding.

Answer 148

T-arm

T-arm Tethers tRNA to ribosome

Question 149

The _____ of the tRNA contains dihydrouridine residues necessary for tRNA recognition by the correct aminoacyl-tRNA synthetase.

Answer 149

D-arm

D-arm Detects the aminoacyl-tRNA synthetase

Question 150

The _____ is the amino acid acceptor site.

Answer 150

5’-CCA-3’ (Acceptor Stem)

Question 151

_____ scrutinizes the amino acid before and after it binds to tRNA.

Answer 151

Aminoacyl-tRNA Synthetase

Question 152

If incorrect, the tRNA-amino acid bond is _____.

Answer 152

hydrolyzed

Question 153

The tRNA-amino acid bond has energy for the formation of _____.

Answer 153

peptide bond

Question 154

A mischarged tRNA reads the usual codon but _____.

Answer 154

inserts the wrong amino acid

Question 155

_____ and _____ are responsible for the accuracy of amino acid selection.

Answer 155

• Aminoacyl-tRNA Synthetase
• binding of charged tRNA to the codon

Question 156

tRNA charging requires _____.

Answer 156

ATP

ATP = tRNA Activation (charging)

Question 157

tRNA Structure

Answer 157

Question 158

Protein Synthesis Initiation: identify either the 5’ cap or an internal ribosome entry site (IRES)

Answer 158

eukaryotic initiation factors (eIFs)

Question 159

Protein Synthesis Initiation: can be located at many places in an mRNA, most often at the 5’UTR

Answer 159

internal ribosome entry site (IRES)

Question 160

Protein Synthesis Initiation: help assemble the 40S ribosomal subunit with the initiator tRNA and are released when the mRNA and the ribosomal 60S subunit assemble with the complex

Answer 160

eukaryotic initiation factors (eIFs)

Question 161

Protein synthesis initiation requires _____.

Answer 161

GTP

GTP = tRNA Gripping and Going places (translocation)

Question 162

Eukaryotic Ribosomal Subunits

Answer 162

40S + 60S → 80S

Eukaryotes = Even

Question 163

Prokaryotic Ribosomal Subunits

Answer 163

30S + 50S → 70S

prOkaryotes = Odd

Question 164

Protein Elongation Process

Answer 164

1. Aminoacyl-tRNA binds to A site (except for initiator methinine), requires an elongation factor and GTP
2. rRNA (“ribozyme”) catalyzes peptide bond formation, transfers growing polypeptide to amino acid in A site
3. Ribosome advances 3 nucleotides toward 3’ end of mRNA, moving peptidyl tRNA to P site (translocation)

Question 165

Protein Elongation Process: Step 1

Answer 165

Aminoacyl-tRNA binds to A site (except for initiator methinine), requires an elongation factor and GTP

Question 166

Protein Elongation Process: Step 2

Answer 166

rRNA (“ribozyme”) catalyzes peptide bond formation, transfers growing polypeptide to amino acid in A site

Question 167

Protein Elongation Process: Step 3

Answer 167

Ribosome advances 3 nucleotides toward 3’ end of mRNA, moving peptidyl tRNA to P site (translocation)

Question 168

Protein Elongation Process

Answer 168

APE

• A site = incoming Aminoacyl-tRNA
• P site = accommodates growing Peptide
• E site = holds Empty tRNA as it Exits

Question 169

Posttranslational Modifications:

removal of N- or C-terminaal propeptides from zymogen to generate mature protein (e.g. trypsinogen → trypsin

Answer 169

Trimming

Question 170

Posttranslational Modifications:

Covalent Alterations

Answer 170

• phosphorylation
• glycosylation
• hydroxylation
• methylation
• acetylation
• ubiquitination

Question 171

Posttranslational Modifications:

intracellular protein involved in facilitationg and/or maintaining protein folding

Answer 171

Chaperone Protein

Question 172

Cell cycle phases are regulated by _____,

Answer 172

• cyclins
• cyclin-dependent kinases (CDKs)
• tumor suppressors

Question 173

The _____ is the shortest phase of the cell cycle and includes _____.

Answer 173

M Phase

• Mitosis
• Cytokinesis

Question 174

Mitosis Steps

Answer 174

1. Prophase
2. Prometaphase
3. Metaphase
4. Anaphase
5. Telophase

Question 175

_____ occurs when the cytoplasm splits into 2.

Answer 175

Cytokinesis

Question 176

Cell Cycle

Answer 176

Question 177

Cell Cycle Regulation:

• constitutive
• inactive

Answer 177

Cyclin-Dependent Kinases (CDKs)

Question 178

Cell Cycle Regulation:

• regulatory proteins to coordinate cell cycle progression
• phase specific
• activate CDKs

Answer 178

Cyclins

Question 179

Cell Cycle Regulation:

• phosphorylate other proteins to coordinate cell cycle progression
• must be activated and inactivated at appropriate times for the cell cycle to progress

Answer 179

Cyclin-CDK Complexes

Question 180

Cell Cycle Regulation:

• supresses cell division
• mutations can lead to tumors

Answer 180

Tumor Suppressors

Question 181

Tumor Suppression

Answer 181

p53 induces p21 → inhibits CDKs → hypophosphrylation (activation) of Rb → inhibition of G1-S progression

Question 182

Growth factors bind _____ to transition the cell from G₁ to S phase.

Answer 182

tyrosine kinase receptors

Question 183

Cell Types:

• remain in G₀
• regenerate from stem cells
• neurons, skeletal and cardiac muscle, RBCs

Answer 183

Permanent

Question 184

Cell Types:

• enter G₁ from G₀ when stimulated
• hepatocytes, lymphocytes, PCT, periosteal cells

Answer 184

Stable (Quiescent)

Question 185

Cell Types:

• never go to G₀
• divide rabpidly with a short G₁
• most affeced by chemotherapy
• bone marrow, gut epithelium, skin, hair follicles, germ cells

Answer 185

Labile

Question 186

The _____ is the site of synthesis of secretpry ((exported) proteins and of N-linked oligosaccharide addition to many proteins.

Answer 186

Rough Endoplasmic Reticulum

Question 187

_____ are RER in neurons which synthesize peptide neurotansmitters for secretion.

Answer 187

Nissl Bodies

Question 188

_____ are the site of synthesis of cytosolic and organellar proteins.

Answer 188

Free Ribosomes

Question 189

Mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells are rich in _____.

Answer 189

RER

Question 190

The _____ is the site of steroid synthesis and detoxification of drugs and poisons.

Answer 190

Smooth Endoplasmic Reticulum

Question 191

Liver hepatocytes and steroid hormone-producing cells of the adrenal cortex and gonads are rich in _____.

Answer 191

SER

Question 192

Cell Trafficking

Answer 192

Question 193

The _____ is the distribution center for proteins and lipids from the ER to the vesicles and plasma membrane.

Answer 193

Golgi Apparatus

Question 194

The golgi apparatus modifies N-oligosaccharides on _____.

Answer 194

Asparagine

Question 195

The golgi apparatus adds O-oligosaccharides on _____.

Answer 195

Serine

Threonine

Question 196

The golgi apparatus adds _____ to proteins for trafficking to lysosomes.

Answer 196

mannose-6-phosphate

Question 197

_____ are sorting centers for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use.

Answer 197

Endosomes

Question 198

_____ is an inherited lysosomal storage disorder which causes coarse facial features, gingival hyerplasia, clouded corneas, restricted joint movements, clawhand deformities, kyphoscoliosis and high levels of lysosomal enzymes. It is often fatal in childhood.

Answer 198

Inclusion Cell Disease

(I-Cell DIsease/Mucolipidosis type II)

Question 199

Inclusion Cell Disease Pathogensis

Answer 199

defect in N-acetylglucosaminyl-1-phosphotransferase → failure of the Golgi to phosphorylate mannose residues (↓ mannose-6-phosphate) on glycoproteins → proteins are secreted extracellularly rather than delivered to lysosomes

Question 200

_____ is an abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER.

Answer 200

Signal Recognition Paticle (SRP)

Question 201

Absent or dysfunctional _____ leads to protein accumulation in the cytosol.

Answer 201

SRP

Question 202

Vesicular Trafficking Proteins:

• Golgi → Golgi (retrograde)
• cis-Golgi → ER

Answer 202

COPI

Question 203

Vesicular Trafficking Proteins:

ER → cis-Golgi (anterograde)

Answer 203

COPII

Question 204

Vesicular Trafficking Proteins:

• trans-Golgi → lysosomes
• plasma membranes → endosomes (receptor -mediated endocytosis)

Answer 204

Clathrin

Question 205

_____ are membrane-enclosed organelles involved in :

• β-oxidation of very-long-chain fatty acids (VLCFA)
• α-oxidation
• catabolism of branched-chain fatty acids, amino acids and ethanol
• synthesis of cholesterol, bile acids and plasmalogens (important membrane phospholipid, especially in white matter of brain)

Answer 205

Peroxisomes

Question 206

_____ is an autosomal recessive disorder of peroxisome biogenesis due to mutated PEX genes cauzing hypotonia, seizures, hepatomegaly and early death.

Answer 206

Zellweger Syndrome

Question 207

_____ is an autosomal recessive disorder of α-oxidation → phytanic acid is not metabolized to pristanic acid causing scaly skin, ataxia, cataracts, night blindness, shortening of the 4th toe, epiphyseal dysplasia.

Answer 207

Refsum Disease

Question 208

Refsum Disease:

Treatment

Answer 208

diet

plasmapheresis

Question 209

_____ is an X-linked recessive disorder of β-oxidation → VLCFA buildup in adrenal glands, white matter and testes → adrenal gland crisis, coma and death.

Answer 209

Adrenoleukodystrophy

Question 210

The _____ is a barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins.

Answer 210

Proteasome

Question 211

Defects in the _____ have been implicated in some cases of Parkinson Disease.

Answer 211

Ubiquitin-Proteasome System

Question 212

_____ is a network of protein fibers within the cytoplasm that supports cell structure, cell and organelle movement and cell division.

Answer 212

Cytoskeletal Elements

Question 213

Types of Filaments:

• muscle contraction
• cytokinesis

Answer 213

Microfilaments

Question 214

Types of Filaments:

• actin

Answer 214

Microfilaments

Question 215

Types of Filaments:

• microvilli

Answer 215

Microfilaments

Question 216

Types of Filaments:

maintains cell structure

Answer 216

Intermediate Filaments

Question 217

Types of Filaments:

vimentin

Answer 217

Intermediate Filaments

Question 218

Types of Filaments:

desmin

Answer 218

Intermediate Filaments

Question 219

Types of Filaments:

cytokeratin

Answer 219

Intermediate Filaments

Question 220

Types of Filaments:

lamins

Answer 220

Intermediate Filaments

Question 221

Types of Filaments:

glial fibrillary acidic protein (GFAP)

Answer 221

Intermediate Filaments

Question 222

Types of Filaments:

neurofilaments

Answer 222

Intermediate Filaments

Question 223

Types of Filaments:

• movement
• cell division

Answer 223

Microtubules

Question 224

Types of Filaments:

cilia

Answer 224

Microtubules

Question 225

Types of Filaments:

flagella

Answer 225

Microtubules

Question 226

Types of Filaments:

mitotic spindle

Answer 226

Microtubules

Question 227

Types of Filaments:

axonal trafficking

Answer 227

Microtubules

Question 228

Types of Filaments:

centrioles

Answer 228

Microtubules

Question 229

_____ have a cylindrical outer structure composed of a helical array of polymerized heterodimers of α- and β-tubulin.

Answer 229

Microtubules

Question 230

Each dimer on a microtubule has a _____ bond.

Answer 230

2 GTP

Question 231

_____ are incorporated into flagella, cilia and mitotic spindles.

Answer 231

Microtubules

Question 232

Microtubules grow _____ and collapse _____.

Answer 232

grow slowly

collapse quickly

Question 233

Microtubule Structure

Answer 233

Question 234

_____ transport cellular cargo toward opposite ends of microtubule tracks.

Answer 234

Molecular Motor Proteins

Question 235

Molecular Motor Proteins:

retrograde to microtubule (+ → -)

Answer 235

Dynein

Negative end Near Nucleus

Question 236

Molecular Motor Proteins:

anterograde to microtubule (- → +)

Answer 236

Kinesin

Positive end Points to Periphery

Question 237

Drugs that act on Microtubules

Answer 237

Microtubules Get Constructed Very Poorly

• Mebendazole (antihelmintic)
• Griseofulvin (antifungal)
• Colchicine (antigout)
• Vincristine/Vinblastine (anticancer)
• Paclitaxel (anticancer)

Question 238

Cilia microtubules are arranged as _____.

Answer 238

• 9 doublet + 2 singlet
• 9 triplets (basal body)

Question 239

_____ is an ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets.

Answer 239

Axonemal Dynein

Question 240

_____ enable coordinated ciliary movement.

Answer 240

Gap Junctions

Question 241

_____ is an autosomal recessive disease which causes immotile cilia due to a dynein arm defect. It causes ↓ fertility due to immotile sperm and dysfunctional fallopian tube cilia (↑ ectopic pregnancy). It also presents with bronchiectasis, recurrent sinusitis, chronic ear infections, conductive hearing loss and situs inversus.

Answer 241

Kartagener Syndrome

(1° Ciliary Dyskinesia)

Question 242

Sodium-Potassium Pump

Answer 242

Question 243

Na⁺-K⁺ ATPase is located in the plasma membrane with the ATP site on the _____.

Answer 243

cytosolic side

Question 244

For each ATP consumed by Na⁺-K⁺ ATPase, _____ go out of the cell and _____ come into the cell.

Answer 244

• 3Na⁺ out - pump phosphorylated
• 2K⁺ in - pump dephosphorylated

Pumpkin = pump K⁺ in

Question 245

The _____ is an asymmetric lipid bilayer containing cholesterol, phospholipids, sphingolipids, glycolipidsand proteins.

Answer 245

plasma membrane

Question 246

_____ inhibits Na⁺-K⁺ ATPase by binding to the K⁺ site.

Answer 246

Ouabain

*cardiac glycoside

Question 247

_____ directly inhibit the Na⁺-K⁺ ATPase, which leads to the indirect inhibition of Na⁺/Ca²⁺ exchange → ↑ [Ca²⁺]_i → ↑ cardiac contractility.

Answer 247

Digoxin and Digitoxin

* cardiac glycosides

Question 248

_____ is the most abundant protein in the body, is extensively modified by posttranslational modification and organizes and strengthens extracellular matrix.

Answer 248

Collagen

Question 249

Collagen Types

Answer 249

Be So Totally Cool, Read Big Books.

1. Bone, Skin, Tendon
2. Cartilage
3. Reticulin, Blood vessels
4. Basement membrane

Question 250

Collagen Types:

most common (90%)

Answer 250

Type I

Question 251

Collagen Types:

bone (made by osteoblasts)

Answer 251

Type I

*↓ production in osteogenesis Imperfecta type I

Question 252

Collagen Types:

skin

Answer 252

Type I

Question 253

Collagen Types:

tendon

Answer 253

Type I

Question 254

Collagen Types:

dentin

Answer 254

Type I

Question 255

Collagen Types:

fascia

Answer 255

Type I

Question 256

Collagen Types:

cornea

Answer 256

Type I

Question 257

Collagen Types:

late wound repair

Answer 257

Type I

Question 258

Collagen Types:

cartilage

Answer 258

Type II

CarTWOlage

Question 259

Collagen Types:

vitreous body

Answer 259

Type II

Question 260

Collagen Types:

nucleus pulposus

Answer 260

Type II

Question 261

Collagen Types:

reticulin

Answer 261

Type III

Question 262

Collagen Types:

blood vessels

Answer 262

Type III

Question 263

Collagen Types:

uterus

Answer 263

Type III

Question 264

Collagen Types:

fetal tissue

Answer 264

Type III

Question 265

Collagen Types:

granulation tissue

Answer 265

Type III

Question 266

Collagen Types:

deficient in the uncommon, vascular type of Ehlers-Danlos syndrome

Answer 266

Type III

Ehlers-Danlos = ThreE D

Question 267

Collagen Types:

basement membrane

Answer 267

Type IV

Type 4 = under the floor (basement)

Question 268

Collagen Types:

basal lamina

Answer 268

Type IV

Question 269

Collagen Types:

lens

Answer 269

Type IV

Question 270

Collagen Synthesis and Structure

Answer 270

Question 271

Collagen Synthesis

Answer 271

1. Synthesis
2. Hydroxylation
3. Glycosylation
4. Exocytosis
5. Proteolytic Processing
6. Cross-Linking

Question 272

Collagen synthesis begins with the translation of _____.

Answer 272

collagen α chains

(preprocollagen)

*usually Gly-X-Y

*X - proline

*Y - lysine

Question 273

_____ content best reflects collagen synthesis.

Answer 273

Glycine

*collagen is 1/3 glycine

Question 274

During collagen synthesis, _____ redidues are hydroxylated.

Answer 274

proline

lysine

Question 275

Collagen hydroxylation requires _____.

Answer 275

Vitamin C

*deficiency → scurvy

Question 276

During collagen synthesis, _____ are glycosylated.

Answer 276

pro-α-chain hydroxylysine residues

Question 277

During collagen glycosylation, procollagen is formed via _____.

Answer 277

hydrogen and disulfide bonds

(triple helix of 3 collagen α chains)

*problems forming triple helix → osteogenesis imperfecta

Question 278

During collagen synthesis, _____ is exocytosed into the extracellular space.

Answer 278

procollagen

Question 279

During proteolytic processing of collagen, cleavage of disulfide-rich terminal regions of procollagen forms _____.

Answer 279

insoluble tropocollagen

*problems with cleavage → Ehlers-Danlos

Question 280

During collagen cross-linking, staggered tropocollagen molecules are reinforced by _____ to make collagen fibrils.

Answer 280

covalent lysine-hydroxylisine cross-linkage

(by copper-containing lysyl oxidase)

*problems with cross-linking → Ehler-Danlos, Menkes

Question 281

_____ is a genetic bone disorder caused by a variety of gene defeccts (most commonly COL1A1 and COL1A2).

Answer 281

Osteogenesi Imperfecta

(brittle bone disease)

Question 282

The most common form of osteogenesis imperfecta in _____ with ↓ production of _____.

Answer 282

autosomal dominant

Type I collagen

Question 283

Osteogenesis Imperfecta Manifestations

Answer 283

Patients cam’t BITE.

• Bones = multiple fractures with minimal trauma
• I (eye) = blue sclerae - translucent connective tissue overchoroidal veins
• Teeth = tooth abnormalities - opalescent teeth that wear easily due to lack of dentin (dentinogenesis imperfecta)
• Ear = hearing loss (abnormal ossicles)

Question 284

Osteogenesis Imperfecta is treated with _____.

Answer 284

biphosponates

Question 285

_____ is a disease with faulty collagen synthesis causing hyperextensible skin, hypermobile joints and a tendency to bleed (easy bruising).

Answer 285

Ehlers-Danlos Syndrome

Question 286

The most common type of Ehlers-Danlos Syndrome is _____.

Answer 286

Hypermobility Type

(joint instability)

Question 287

The classical type of Ehlers-Danlos Syndrome is caused by a mutation in _____.

Answer 287

Type V Collagen

(joint and skin)

Question 288

The vascular type of Ehlers-Danlos Syndrome is caused by a deficiency in _____ which affects fragile tissues, vessels, muscles and organs that are prone to rupture.

Answer 288

Type III Procollagen

Question 289

_____ disease is an X-linked recessive connective tissue disease caused by impaired copper absorption and transfport due to defective ATP7A (_____ protein).

Answer 289

Menkes

Question 290

Menkes disease causes ↓ activity of _____ → defective collagen.

Answer 290

lysyl oxidase

*copper is a necessary cofactor

Question 291

_____ disease causes brittle, “kinky” hair, growth retardation and hypotonia.

Answer 291

Menkes

Question 292

_____ is a stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords and ligamenta flava.

Answer 292

Elastin

Question 293

Elastin Structure

Answer 293

Question 294

Elastin is rich in _____.

Answer 294

nonhydroxylated proline, glycine and lysine residues.

Question 295

Elastin is composed of _____.

Answer 295

tropoelastin with fibrillin scaffolding

Question 296

Elastin cross-linking takes place _____ and gives it elastic properties.

Answer 296

extracellularly

Question 297

Elastin is broken down by _____.

Answer 297

Elastase

Question 298

Elastase is inhibited by _____.

Answer 298

α₁-antitrypsin

Question 299

_____ deficiency results in unopposed elastase activity which can cause emphysema.

Answer 299

α₁-antitrypsin

Question 300

Changes with Aging

Answer 300

• ↓ dermal collagen and elastin
• ↓ synthesis of collagen fibrils
• crosslinking remains normal

Question 301

_____ is an autosomal dominant connective tissue disorder affecting skeleton, heart and eyes because of FBN1 gene mutation on chromosome 15.

Answer 301

Marfan Syndrome

Question 302

In Marfan Syndrome, FBN1 gene mutation on chromosome 15 results in defective _____, a glycoprotein that forms a sheath around elastin.

Answer 302

fibrillin

Question 303

_____ manifests with tall stature, long extremities, pectus carinatum (more specific) or pectus excavatum, hypermobile joints, long tapering fingers and toes (arachnodactyly), cystic medial necrosis of the aorta, aortic incompetence, dissecting aortic aneurysms, floppy mitral valve and subluxation of lenses (upward and temporally).

Answer 303

Marfan Syndrome

Question 304

_____ is a molecular biology lab procedure used to amplify a desired fragment of DNA.

Answer 304

Polymerase Chain Reaction

Question 305

Polymerase Chain Reaction

Answer 305

Question 306

Polymerase Chain Reaction

Answer 306

1. Denaturation
2. Annealing
3. Elongation

Question 307

In PCR, DNA is heated to _____ to separate strands.

Answer 307

95°C

Question 308

During the annealing process of PCR, the sample is cooled to _____.

Answer 308

55°C

Question 309

During the annealing process of PCR, _____ are added.

Answer 309

• DNA primers
• heat-stable DNA polymerase (Taq)
• deoxynucleotide triphosphates (dNTPs)

Question 310

During the elongation process of PCR, the temperature is increased to _____.

Answer 310

72°C

Question 311

During the elongation process of PCR, DNA polymerase attaches _____ to the strand to replicate the sequence after each primer.

Answer 311

dNTPs

Question 312

_____ is a genome editing tool derived from bacteria.

Answer 312

CRISPR

Question 313

CRISPR is composed of an endonuclease, _____, which cleaves dsDNA and a guide RNA (gRNA) sequence that binds to complementary target DNA sequence.

Answer 313

Cas9

Question 314

CRISPR:

cell DNA repair machinery (nonhomologous end joining) fills in the gap introduced by the system

Answer 314

knock-out

knock-out = removing a gene, taking it out

Question 315

CRISPR:

a donor DNA can be added to the system to fill the gap

Answer 315

knock-in

knock-in = inserting a gene.

Question 316

Blotting Procedures

Answer 316

SNoW DRoP

• Southern = DNA
• Northern = RNA
• Western = Protein

Question 317

Southern Blot

Answer 317

Question 318

Southern Blot Procedure

Answer 318

1. DNA sample is enzymatically cleaved into smaller pieces,which are separated on a gel by electrophoresis, and then transferred to a filter.
2. Filter is exposed to radiolabeled DNA probe that recognizes and anneals to its complementary strand.
3. Resulting double-stranded, labeled piece of DNA is visualized when filter is exposed to film.

Question 319

_____ is similar to Southern Blot, except that an RNA sample is electrophoresed. It is useful of studying mRNA levels, which are reflective of gene expression.

Answer 319

Northern Blot

Question 320

In _____, a sample protein is separated via gel electrophoresis and transferred to a membrane. The labeled antibody is used to bind to relevant protein.

Answer 320

Western Blot

Question 321

_____ identifies DNA-binding proteins (eg. transcription factors) using labeled oligonucleotide probes.

Answer 321

Southwestern Blot

Question 322

_____ is a laboratory technique which assesses the size, granularity, and protein expression (immunophenotype) of individual cells in a sample.

Answer 322

Flow Cytometry

Question 323

In _____, cells are tagged with antibodies specific to surface or intracellular proteins. Antibodies are then tagged with a unique fluorescent dye. The sample is analyzed one cell at a time by focusing a laser on the cell and measuring light scatter and intensity of fluorescence.

Answer 323

Flow Cytometry

Question 324

_____ is a laboratory technique commonly used in workup of hematologic abnormalities (eg. paroxysmal nocturnal hemoglobinuria, fetal RBCs in mother’s blood) and immunodeficiencies (eg. CD4 cell count in HIV).

Answer 324

Flow Cytometry

Question 325

Flow Cytometry data are plotted either as _____ or _____.

Answer 325

• histogram (one measure)
• scatter plot (any two measures)

Question 326

Flow Cytometry

Answer 326

Question 327

In _____, thousands of nucleic acid sequences are arranged in grids on glass or silicon. DNA or RNA probes are hybridized to the chip, and a scanner detects the relative amounts of complementary binding.

Answer 327

Microarrays

Question 328

_____ are used to profile gene expression levels of thousands of genes simultaneously to study certain diseases and treatments. Able to detect single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) for a variety of applications including genotyping, clinical genetic testing, forensic analysis, cancer mutations, and genetic linkage analysis.

Answer 328

Microarrays

Question 329

_____ is an immunologic test used to detect the presence of either a specific antigen (eg. HBsAg) or antibody (eg. anti-HBs) in a patient’s blood sample.

Answer 329

Enzyme-Linked Immunosorbent Assay (ELISA)

Question 330

In _____, detection involves the use of an antibody linked to an enzyme. Added substrate reacts with enzyme, producing a detectable signal. It can have high sensitivity and specificity, but is less specific than Western blot.

Answer 330

Enzyme-Linked Immunosorbent Assay (ELISA)

Question 331

Direct ELISA tests for the _____.

Answer 331

antigen

Question 332

Indirect ELISA tests for the _____.

Answer 332

antibody

Question 333

_____ is a process in which metaphase chromosomes are stained, ordered, and numbered according to morphology, size, arm-length ratio, and banding pattern.

Answer 333

Karyotyping

Question 334

Karyotyping can be performed on a sample of _____.

Answer 334

• blood
• bone marrow
• amniotic fluid
• placental tissue

Question 335

In _____, a fluorescent DNA or RNA probe binds to
specific gene site of interest on chromosomes. Used for specific localization of genes and direct
visualization of chromosomal anomalies at the
molecular level.

Answer 335

Fluorescence In Situ Hybridization (FISH)

Question 336

FISH:

no fluorescence on a chromosome compared to fluorescence at the same locus on the second copy of that chromosome

Answer 336

Microdeletion

Question 337

FISH:

fluorescence signal that corresponds to one chromosome is found in a different chromosome

Answer 337

Translocation

Question 338

FISH:

a second copy of a chromosome, resulting in a trisomy or tetrasomy

Answer 338

Duplication

Question 339

_____ is the production of a recombinant DNA molecule in a bacterial host.

Answer 339

Molecular Cloning

Question 340

Molecular Cloning

Answer 340

1. Isolate eukaryotic mRNA (post-RNA processing) of interest.
2. Add reserve transcriptase (an RNA-dependent DNA polymerase) to produce complementary DNA (cDNA, lacks introns).
3. Insert cDNA fragments into bacterial plasmids containing antibiotic resistance genes.
4. Transform (insert) recombinant plasmid into bacteria.
5. Surviving bacteria on antibiotic medium produce cloned DNA (copies of cDNA).

Question 341

Transgenic strategies in mice involve _____.

Answer 341

• Random insertion of gene into mouse genome
• Targeted insertion or deletion of gene through homologous recombination with mouse gene

Question 342

Gene Expression Modifications:

Random Insertion

Answer 342

Constitutive

Question 343

Gene Expression Modifications:

Targeted Insertion

Answer 343

Conditional

Question 344

_____ can inducibly manipulate genes at specific developmental points (eg. to study a gene whose deletion causes embryonic death).

Answer 344

Cre-Lox System

Question 345

In _____, dsRNA is synthesized that is complementary to the mRNA sequence of interest. When transfected into human cells, dsRNA separates and promotes degradation of target mRNA, “knocking down” gene expression.

Answer 345

RNA Interference

Question 346

Genetics:

both alleles contribute to the phenotype of the heterozygote

Answer 346

Codominance

Question 347

Genetics:

• blood groups A, B, AB
• α1-antitrypsi deficiency
• HLA groups

Answer 347

Codominance

Question 348

Genetics:

patients with the same genotype have varying phenotypes

Answer 348

Variable Expressivity

Question 349

Genetics:

2 patients with neurofibromatosis type 1 (NF1) may have varying disease severity

Answer 349

Variable Expressivity

Question 350

Genetics:

not all individuals with a mutant genotype show the mutant phenotype

Answer 350

Incomplete Penetrance

% penetrance × probability of inheriting genotype = risk of expressing phenotype.

Question 351

Genetics:

BRCA1 gene mutations do not always result in breast or ovarian cancer

Answer 351

Incomplete Penetrance

Question 352

Genetics:

one gene contributes to multiple phenotypic effects

Answer 352

Pleiotropy

Question 353

Genetics:

untreated phenylketonuria (PKU) manifests with light skin, intellectual disability, and musty body odor

Answer 353

Pleiotropy

Question 354

Genetics:

increased severity or earlier onset of disease in succeeding generations

Answer 354

Anticipation

Question 355

Genetics:

trinucleotide repeat diseases (eg. Huntington disease)

Answer 355

Anticipation

Question 356

Genetics:

if a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops (not true of oncogenes)

Answer 356

Loss of Heterozygosity

Question 357

Genetics:

• Retinoblastoma and the “two-hit hypothesis”
• Lynch Syndrome (HNPCC)
• Li-Fraumen Syndrome

Answer 357

Loss of Heterozygosity

Question 358

Genetics:

exerts a dominant effect, a heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning

Answer 358

Dominant Negative Mutation

Question 359

Genetics:

mutation of a transcription factor in its allosteric site, nonfunctioning mutant can still bind DNA preventing wild-type transcription factor from binding

Answer 359

Dominant Negative Mutation

Question 360

Genetics:

tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance, measured in a population, not in a family, and often varies in different populations

Answer 360

Linkage Disequilibrium

Question 361

Genetics:

presence of genetically distinct cell lines in the
same individual

Answer 361

Mosaicism

Question 362

Genetics:

mutation arises from mitotic errors after fertilization and propagates through multiple tissues or organs

Answer 362

Somatic Mosaicism

Question 363

Genetics:

mutation only in egg or sperm cells, if parents and relatives do not have the disease suspect gonadal (or germline) mosaicism

Answer 363

Gonadal Mosaicism

Question 364

_____ is due to a mutation affecting G-protein signaling. It presents with unilateral café-au-lait spots with ragged edges, polyostotic fibrous dysplasia (bone is replaced by collagen and fibroblasts), and at least one endocrinopathy (eg. precocious puberty). Lethal if mutation occurs before fertilization (affecting all cells), but survivable in patients with mosaicism.

Answer 364

McCune-Albright Syndrome

Question 365

Genetics:

mutations at different loci can produce a similar phenotype

Answer 365

Locus Heterogeneity

Question 366

Genetics:

albinism

Answer 366

Locus Heterogeneity

Question 367

Genetics:

different mutations in the same locus produce the same phenotype

Answer 367

Allelic Heterogeneity

Question 368

Genetics:

β-thalassemia

Answer 368

Allelic Heterogeneity

Question 369

Genetics:

presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease

Answer 369

Heteroplasmy

Question 370

Genetics:

mtDNA passed from mother to all children

Answer 370

Heteroplasmy

Question 371

Genetics:

offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent

Answer 371

Uniparental Disomy

Question 372

Heterodisomy (heterozygous) indicates a _____.

Answer 372

meiosis I error

HeterodIsomy = meiosis I error

Question 373

Isodisomy (homozygous) indicates a _____ or postzygotic chromosomal duplication of one of a pair of chromosomes, and loss of the other of the original pair.

Answer 373

meiosis II error

IsodIsomy = meiosis II error

Question 374

Uniparental disomy (UPD) is _____. Most occurrences of uniparental disomy → normal phenotype. Consider UPD in an individual manifesting a recessive disorder when only one parent is a carrier. Examples: Prader Willi and Angelman Syndromes

Answer 374

euploid

(correct number of chromosomes)

Question 375

Genetics:

Prader Willi and Angelman Syndromes

Answer 375

Uniparental Disomy

Question 376

If a population is in Hardy-Weinberg equilibrium and if p and q are the frequencies of separate alleles, then _____.

Answer 376

p² + 2pq + q² = 1 and p + q = 1, which implies that:

• p² = frequency of homozygosity for allele A
• q² = frequency of homozygosity for allele a
• 2pq = frequency of heterozygosity (carrier frequency, if an autosomal recessive disease).

The frequency of an X-linked recessive disease in males = q and in females = q2.

Question 377

Hardy-Weinberg law assumptions include:

Answer 377

• No mutation occurring at the locus
• Natural selection is not occurring
• Completely random mating
• No net migration

Question 378

Genetics:

one gene copy is silenced by methylation, and only the other copy is expressed → parent-of-origin effects

Answer 378

Imprinting

Question 379

_____ occurs when maternally derived genes are silenced (imprinted). Disease occurs when the paternal allele is deleted or mutated. Results in hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia. Associated with a mutation or deletion of chromosome 15 of paternal origin. 25% of cases due to maternal uniparental disomy.

Answer 379

Prader-Willi Syndrome

Prader-Willi = Paternal

Question 380

_____ occurs when paternally derived UBE3A gene is silenced (imprinted). Disease occurs when the maternal allele is deleted or mutated. Results in inappropriate laughter (“happy puppet”), seizures, ataxia, and severe intellectual disability. Associated with mutation or deletion of the UBE3A gene on the maternal copy of chromosome 15. 5% of cases due to paternal uniparental disomy.

Answer 380

Angelman Syndrome

AngelMan = Maternal

Question 381

Modes of Inheritance

Answer 381

Autosomal Dominant

Question 382

Modes of Inheritance

Answer 382

Autosomal Recessive

Question 383

Modes of Inheritance

Answer 383

X-linked Recessive

Question 384

Modes of Inheritance

Answer 384

X-linked Dominant

Question 385

Modes of Inheritance

Answer 385

Mitochondrial Inheritance

Question 386

Modes of Inheritance:

• often due to defects in structural genes
• many generations, both males and females are affected
• often pleiotropic (multiple apparently unrelated effects) and variably expressive (different between individuals)
• with one affected (heterozygous) parent 1/2 of children are affected.

Answer 386

Autosomal Dominant

Question 387

Modes of Inheritance:

• often due to enzyme deficiencies
• usually seen in only 1 generation
• commonly more severe than dominant disorders
• patients often present in childhood.
• ↑ risk in consanguineous families.
• With 2 carrier (heterozygous) parents, on average: ¼ of children will be affected (homozygous), ½ of children will be carriers, and ¼ of children will be neither affected nor carriers.

Answer 387

Autosomal Recessive

Question 388

Modes of Inheritance:

• sons of heterozygous mothers have a 50% chance of being affected
• no male-to-male transmission
• skips generations
• commonly more severe in males
• females usually must be homozygous to be affected

Answer 388

X-linked Recessive

Question 389

Modes of Inheritance:

• transmitted through both parents
• mothers transmit to 50% of daughters and sons
• fathers transmit to all daughters but no sons

Answer 389

X-linked Dominant

Question 390

Modes of Inheritance:

Hypophosphatemic Rickets

Answer 390

X-linked Dominant

Question 391

Modes of Inheritance:

Fragile X Syndrome

Answer 391

X-linked Dominant

Question 392

Modes of Inheritance:

Alport Syndrome

Answer 392

X-linked Dominant

Question 393

_____, formerly known as vitamin D-resistant rickets, is an inherited disorder resulting in ↑ phosphate wasting at the proximal tubule.

Answer 393

Hypophosphatemic Rickets

Question 394

Modes of Inheritance:

• transmitted only through the mother
• all offspring of affected females may show signs of disease
• variable expression in a population or even within a family due to heteroplasmy

Answer 394

Mitochondrial Inheritance

Question 395

Modes of Inheritance:

Mitochondrial Myopathies

Answer 395

Mitochondrial Inheritance

Question 396

Modes of Inheritance:

Leber Hereditary Optic Neuropathy

Answer 396

Mitochondrial Inheritance

Question 397

_____ are rare disorders, often presenting with myopathy, lactic acidosis, and CNS disease.

Answer 397

Mitochondrial Myopathies

Question 398

_____ is 2° to failure in oxidative phosphorylation. Muscle biopsy often shows “ragged red fibers” (due to accumulation of diseased mitochondria).

Answer 398

MELAS Syndrome

• Mitochondrial Encephalomyopathy
• Lactic Acidosis
• Stroke-like episodes

Question 399

_____ causes cell death in optic nerve neurons → subacute bilateral vision loss in teens/young adults, 90% males. It is usually permanent.

Answer 399

Leber Hereditary Optic Neuropathy

Question 400

Modes of Inheritance:

Achondroplasia

Answer 400

Autosomal Dominant

Question 401

Modes of Inheritance:

Familial Adenomatous Polyposis

Answer 401

Autosomal Dominant

Question 402

Modes of Inheritance:

Familial Hypercholesterolemia

Answer 402

Autosomal Dominant

Question 403

Modes of Inheritance:

Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome)

Answer 403

Autosomal Dominant

Question 404

Modes of Inheritance:

Hereditary Spherocytosis

Answer 404

Autosomal Dominant

Question 405

Modes of Inheritance:

Huntington Disease

Answer 405

Autosomal Dominant

Question 406

Modes of Inheritance:

Li-Fraumeni Syndrome

Answer 406

Autosomal Dominant

Question 407

Modes of Inheritance:

Marfan Syndrome

Answer 407

Autosomal Dominant

Question 408

Modes of Inheritance:

Multiple Endocrine Neoplasias

Answer 408

Autosomal Dominant

Question 409

Modes of Inheritance:

Myotonic Muscular Dystrophy

Answer 409

Autosomal Dominant

Question 410

Modes of Inheritance:

Neurofibromatosis Type 1

(von Recklinghausen Disease)

Answer 410

Autosomal Dominant

Question 411

Modes of Inheritance:

Neurofibromatosis Type 2

Answer 411

Autosomal Dominant

Question 412

Modes of Inheritance:

Tuberous Sclerosis

Answer 412

Autosomal Dominant

Question 413

Modes of Inheritance:

von Hippel-Lindau Disease

Answer 413

Autosomal Dominant

Question 414

Modes of Inheritance:

Albinism

Answer 414

Autosomal Recessive

Question 415

Modes of Inheritance:

Cystic Fibrosis

Answer 415

Autosomal Recessive

Question 416

Modes of Inheritance:

Friedreich Ataxia

Answer 416

Autosomal Recessive

Question 417

Modes of Inheritance:

Glycogen Storage Diseases

Answer 417

Autosomal Recessive

Question 418

Modes of Inheritance:

Hemochromatosis

Answer 418

Autosomal Recessive

Question 419

Modes of Inheritance:

Kartagener Syndrome

Answer 419

Autosomal Recessive

Question 420

Modes of Inheritance:

Mucopolysaccharidoses
(except Hunter Syndrome)

Answer 420

Autosomal Recessive

Question 421

Modes of Inheritance:

Phenylketonuria

Answer 421

Autosomal Recessive

Question 422

Modes of Inheritance:

Sickle Cell Anemia

Answer 422

Autosomal Recessive

Question 423

Modes of Inheritance:

Sphingolipidoses

(except Fabry Disease)

Answer 423

Autosomal Recessive

Question 424

Modes of Inheritance:

Thalassemias

Answer 424

Autosomal Recessive

Question 425

Modes of Inheritance:

Wilson Disease

Answer 425

Autosomal Recessive

Question 426

_____ is an autosomal recessive disease caused by a defect in CFTR gene on chromosome 7, commonly a deletion of Phe508.

Answer 426

Cystic Fibrosis

Question 427

_____ is the most common lethal genetic disease in Caucasian population.

Answer 427

Cystic Fibrosis

Question 428

• CFTR encodes an ATP-gated Cl⁻ channel that secretes Cl⁻ in lungs and GI tract, and reabsorbs Cl⁻ in sweat glands.
• Most common mutation: misfolded protein → protein retained in RER and not transported to cell membrane, causing ↓ Cl⁻ (and H₂O) secretion; ↑ intracellular Cl⁻ results in compensatory ↑ Na⁺ reabsorption via epithelial Na+ channels → ↑ H₂O reabsorption → abnormally thick mucus secreted into lungs and GI tract.
• ↑ Na⁺ reabsorption also causes more negative transepithelial potential difference.

Answer 428

Cystic Fibrosis

Question 429

• ↑ Cl⁻ concentration in pilocarpine-induced sweat test is diagnostic.
• Can present with contraction alkalosis and hypokalemia (ECF effects analogous to a patient taking a loop diuretic) because of ECF H₂O/Na⁺ losses and concomitant renal K⁺/H⁺ wasting.
• ↑ immunoreactive trypsinogen (newborn screening).

Answer 429

Cystic Fibrosis

Question 430

• Recurrent pulmonary infections (eg. S aureus [early infancy], P aeruginosa [adolescence]), chronic bronchitis and bronchiectasis → reticulonodular pattern on CXR, opacification of sinuses.
• Pancreatic insufficiency, malabsorption with steatorrhea, fat-soluble vitamin deficiencies (A, D, E, K), biliary cirrhosis, liver disease.
• Meconium ileus in newborns.
• Infertility in men (absence of vas deferens, spermatogenesis may be unaffected) and subfertility in women (amenorrhea, abnormally thick cervical mucus).
• Nasal polyps, clubbing of nails.

Answer 430

Cystic Fibrosis

Question 431

Cystic Fibrosis Treatment

Answer 431

• Multifactorial: chest physiotherapy, albuterol, aerosolized dornase alfa (DNase), and hypertonic saline facilitate mucus clearance. Azithromycin used as anti-inflammatory agent. Ibuprofen slows disease progression.
• In patients with Phe508 deletion: combination of lumacaftor (corrects misfolded proteins and improves their transport to cell surface) and ivacaftor (opens Cl^– channels → improved chloride transport).

Question 432

X-linked Recessive Disorders

Answer 432

Oblivious Female Will Often Give Her Boys Her x-Linked Disorders

• Ornithine Transcarbamylase Deficiency
• Fabry Disease
• Wiskott-Aldrich Syndrome
• Ocular Albinism
• G6PD Deficiency
• Hunter Syndrome
• Bruton Agammaglobulinemia
• Hemophilia A and B
• Lesch-Nyhan Syndrome
• Duchenne (and Becker) Muscular Dystrophy

Question 433

In _____, female carriers are variably affected depending on the pattern of inactivation of the X chromosome carrying the mutant vs. normal gene.

Answer 433

X-Inactivation

(Lyonization)

Question 434

Females with _____ are more likely to have an X-linked recessive disorder.

Answer 434

Turner Syndrome (45,XO)

Question 435

_____ is an X-linked disorder typically due to frameshift or nonsense mutations → truncated or absent dystrophin protein → progressive myofiber damage.

Answer 435

Duchenne Muscular Dystrophy

Question 436

In Duchenne Muscular Dystrophy, weakness begins in the _____ and progresses _____ leading to a _____ gait.

Answer 436

pelvic girdle muscles

superiorly

waddling

Question 437

In Duchenne Muscular Dystrophy, pseudohypertrophy of calf muscles is due to _____.

Answer 437

fibrofatty replacement of muscle

Question 438

The onset of Duchenne Muscular Dystrophy is _____.

Answer 438

before 5 y.o.

Question 439

In Duchenne Muscular Dystrophy, the most common cause of death is _____.

Answer 439

dilated cardiomyopathy

Question 440

_____ is deomonstrated when a patient uses upper extremities to help stand up.

Answer 440

Gower Sign

Question 441

_____ is the largest protein-coding human gene → ↑ chance of spontaneous mutation.

Answer 441

Dystrophin Gene

Question 442

_____ helps anchor muscle fibers, primarily in skeletal and cardiac muscle. It connects the intracellular cytoskeleton (actin) to the transmembrane proteins α- and β-dystroglycan, which are connected to the extracellular matrix (ECM).

Answer 442

Dystrophin

Question 443

_____ presents with ↑ CK and aldolase; genetic testing confirms the diagnosis.

Answer 443

Duchenne Muscular Dystrophy

Question 444

Duchenne Muscular Dystrophy

Answer 444

Question 445

_____ is an X-linked disorder typically due to nonframeshift deletions in dystrophin gene
(partially functional instead of truncated).

Answer 445

Becker Muscular Dystrophy

*less severe than Duchenne

Question 446

Th onset of Becker Muscular Dystrophyis in _____.

Answer 446

adolescence
early adulthood

Question 447

_____ is an autosomal dominant disease. CTG trinucleotide repeat expansion in the DMPK gene → abnormal expression of myotonin protein kinase → myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia.

Answer 447

Myotonic Type 1 Muscular Dystrophy

CTG trinucleotide repeat

• Cataracts
• Toupee (early balding in men)
• Gonadal atrophy

Question 448

_____ is a sporadic disorder seen almost exclusively in girls (affected males die in utero or shortly after birth). Most cases are caused by de novo mutation of MECP2 on X chromosome.

Answer 448

Rett Syndrome

Question 449

The symptoms of Rett Syndrome usually appear between _____.

Answer 449

1-4 y.o.

Question 450

Rett Syndrome is characterized by _____.

Answer 450

• regression (Retturn) in motor, verbal, and cognitive abilities
• ataxia
• seizures
• growth failure
• stereotyped handwringing

Question 451

_____ is an X-linked Dominant disease. Trinucleotide repeat in FMR1 gene → hypermethylation → ↓ expression.

Answer 451

Fragile X Syndrome

Question 452

_____ is the most common cause of inherited intellectual disability and 2nd most common cause of genetically associated mental deficiency (after Down syndrome).

Answer 452

Fragile X Syndrome

Question 453

_____ presents with post-pubertal macroorchidism (enlarged testes), long face with a large jaw, large everted ears, autism, mitral valve prolapse.

Answer 453

Fragile X Syndrome

Question 454

The trinucleotide repeat expansionin Fragile X Syndrome [(CGG)_n] occurs during _____.

Answer 454

oogenesis

Question 455

Trinucleotide repeat expansion diseases may show _____ (disease severity ↑ and age of onset ↓ in successive generations).

Answer 455

genetic anticipation

Question 456

Trinucleotide Repeat Expansion Diseases

Answer 456

Try (trinucleotide) hunting for my fragile cagefree eggs (X).

• Huntington Disease
• Myotonic Dystrophy
• Fragile X Syndrome
• Friedreich Ataxia

Question 457

Huntington Disease Trinucleotide Repeat

Answer 457

CAG

Caudate has ↓ ACh and GABA

Question 458

Myotonic Gystrophy Trinucleotide Repeat

Answer 458

CTG

• Cataracts
• Toupee (early balding in men)
• Gonadal atrophy

Question 459

Fragile X Syndrome Trinucleotide Repeat

Answer 459

CGG

• Chin (protruding)
• Giant Gonads

Question 460

Friedreich Ataxia Trinucleotide Repeat

Answer 460

GAA

Ataxic GAAit

Question 461

_____ presents with intellectual disability, flat facies, prominent epicanthal folds, single palmar crease, gap between 1st 2 toes, duodenal atresia, Hirschsprung disease, congenital heart disease (eg. atrioventricular septal defect), Brushfield spots, early-onset Alzheimer disease (chromosome 21 codes for amyloid precursor protein) and ↑ risk of ALL and AML.

Answer 461

Down Syndrome

Drinking age (21)

(Trisomy 21)

Question 462

95% of Down Syndrome cases are due to _____.

Answer 462

meiotic nondisjunction

*↑ with advanced maternal age; from 1:1500 in women < 20 to 1:25 in women > 45 years old

Question 463

4% of Down Syndrome cases are due to _____, most typically between _____.

Answer 463

unbalanced Robertsonian translocation

chromosomes 14 and 21

Question 464

Only 1% of Down Syndrome cases are due to _____.

Answer 464

postfertilization mitotic error

Question 465

The incidence of Down Syndrome is _____.

Answer 465

1:700

Question 466

_____ is the most common viable chromosomal disorder and most common cause of genetic intellectual disability.

Answer 466

Down Syndrome

Question 467

First-trimester ultrasound of Down Syndrome commonly shows _____.

Answer 467

↑ nuchal translucency

hypoplastic nasal bone

Question 468

Down Syndrome Findings

Answer 468

The 5 A’s of Down Syndrome:

• Advanced maternal age
• Atresia (duodenal)
• Atrioventricular septal defect
• Alzheimer disease (early onset)
• AML/ALL

Question 469

_____ presents with prominent occiput, rocker-bottom feet, intellectual disability, nondisjunction, clenched fists (with overlapping fingers), low-set ears, micrognathia (small jaw), congenital heart disease. Death usually occurs by age 1.

Answer 469

Edwards Syndrome

Election age (18)

(Trisomy 18)

Question 470

The incidence of Edwards Syndrome is _____.

Answer 470

1:8000

Question 471

_____ is the 2nd most common autosomal trisomy resulting in live birth.

Answer 471

Edwards Syndrome

Question 472

Edwards Syndrome Findings

Answer 472

PRINCE Edward

• Prominent occiput
• Rocker-bottom feet
• Intellectual disability
• Nondisjunction
• Clenched fists (with overlapping fingers)
• low-set Ears,

Question 473

_____ presents with severe intellectual disability, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, cutis aplasia, congenital heart disease, polycystic kidney disease. Death usually occurs by age 1.

Answer 473

Patau Syndrome

Puberty (13)

(Trisomy 13)

Question 474

The incidence of Patau Syndrome is _____.

Answer 474

1:15,000

Question 475

Patau Syndrome Findings

Answer 475

The 5 P’s of Patau Syndrome:

• cleft liP/Palate
• holoProsencephaly
• Polydactyly
• cutis aPlasia
• Polycystic kidney disease

Question 476

Trisomies

Answer 476

Question 477

Genetic Disorders:

Chromosome 3

Answer 477

von Hippel-Lindau Disease

Renal Cell Carcinoma

Question 478

Genetic Disorders:

Chromosome 4

Answer 478

ADPKD (PKD2)

Achondroplasia

Huntington Disease

Question 479

Genetic Disorders:

Chromosome 5

Answer 479

Cri-du-chat Syndrome

Familial Adenomatous Polyposis

Question 480

Genetic Disorders:

Chromosome 6

Answer 480

Hemochromatosis (HFE)

Question 481

Genetic Disorders:

Chromosome 7

Answer 481

Williams Syndrome

Cystic Fibrosis

Question 482

Genetic Disorders:

Chromosome 9

Answer 482

Friedreich Ataxia

Tuberous Sclerosis (TSC1)

Question 483

Genetic Disorders:

Chromosome 11

Answer 483

Wilms Tumor

β-globin Gene Defects

(eg. sickle cell disease, β-thalassemia)

MEN1

Question 484

Genetic Disorders:

Chromosome 13

Answer 484

Patau Syndrome

Wilson Disease

Retinoblastoma (RB1)

BRCA2

Question 485

Genetic Disorders:

Chromosome 15

Answer 485

Prader-Willi Syndrome

Angelman Syndrome

Marfan Syndrome

Question 486

Genetic Disorders:

Chromosome 16

Answer 486

ADPKD (PKD1)

α-globin Gene Defects

(eg. α-thalassemia)

Tuberous Sclerosis (TSC2)

Question 487

Genetic Disorders:

Chromosome 17

Answer 487

Neurofibromatosis Type 1

BRCA1

p53

Question 488

Genetic Disorders:

Chromosome 18

Answer 488

Edwards Syndrome

Question 489

Genetic Disorders:

Chromosome 21

Answer 489

Down Syndrome

Question 490

Genetic Disorders:

Chromosome 22

Answer 490

Neurofibromatosis Type 2

DiGeorge Syndrome (22q11)

Question 491

Genetic Disorders:

X Chromosome

Answer 491

Fragile X Syndrome

X-linked Agammaglobulinemia

Klinefelter Syndrome (XXY)

Question 492

_____ is a chromosomal translocation that commonly involves chromosome pairs 13, 14, 15, 21, and 22. It is one of the most common types of translocation. It occurs when the long arms of 2 acrocentric chromosomes (chromosomes with centromeres near their ends) fuse at the centromere and the 2 short arms are lost.

Answer 492

Robertsonian Translocation

Question 493

Unbalanced _____ can result in miscarriage, stillbirth, and chromosomal imbalance (eg. Down Syndrome, Patau Syndrome).

Answer 493

Robertsonian Translocation

Question 494

_____ is caused by the congenital deletion on the short arm of chromosome 5 (46,XX or XY, 5p−).

Answer 494

Cri-du-chat Syndrome

Question 495

_____ presents with microcephaly, moderate to severe intellectual disability, high-pitched crying/ meowing, epicanthal folds, cardiac abnormalities (VSD).

Answer 495

Cri-du-chat Syndrome

Question 496

_____ is caused by the congenital microdeletion of the long arm of chromosome 7 (deleted region includes elastin gene).

Answer 496

Williams Syndrome

Question 497

_____ presents with distinctive “elfin” facies, intellectual disability, hypercalcemia (↑ sensitivity to vitamin D), well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems (eg. supravalvular aortic stenosis, renal artery stenosis).

Answer 497

Williams Syndrome

Question 498

22q11 Deletion Syndromes

Answer 498

DiGeorge Syndrome
Velocardiofacial Syndrome

Question 499

22q11 Deletion Syndrome Findings

Answer 499

CATCH-22

microdeletion at chromosome 22q11 → Cleft palate, Abnormal facies, Thymic aplasia → T-cell deficiency, Cardiac defects, and Hypocalcemia 2° to parathyroid aplasia

Question 500

22q11 Deletion Syndromes result in the aberrant development of the _____.

Answer 500

3rd and 4th branchial (pharyngeal) pouches

Question 501

22q11 Deletion Syndromes:

thymic, parathyroid, and cardiac defects

Answer 501

DiGeorge Syndrome

Question 502

22q11 Deletion Syndromes:

palate, facial, and cardiac defects

Answer 502

Velocardiofacial Syndrome

Question 503

Fat Soluble Vitamins

Answer 503

A, D, E, K

Question 504

Absorption of fat soluble vitamins is dependent on the _____.

Answer 504

gut and pancreas

Question 505

Toxicity more common in fat-soluble
vitamins than for water-soluble vitamins because _____.

Answer 505

fat-soluble vitamins accumulate in fat

Question 506

Malabsorption syndromes with steatorrhea (eg. cystic fibrosis and celiac disease) or mineral oil intake can cause _____.

Answer 506

fat-soluble vitamin deficiencies

Question 507

Water Soluble Vitamins

Answer 507

• B1 (thiamine: TPP)
• B2 (riboflavin: FAD, FMN)
• B3 (niacin: NAD+)
• B5 (pantothenic acid: CoA)
• B6 (pyridoxine: PLP)
• B7 (biotin)
• B9 (folate)
• B12 (cobalamin)
• C (ascorbic acid)

Question 508

B Vitamins

Answer 508

The Regular Night Pub Provided Beer For Coby.

• B1 (Thiamine: TPP)
• B2 (Riboflavin: FAD, FMN)
• B3 (Niacin: NAD+)
• B5 (Pantothenic acid: CoA)
• B6 (Pyridoxine: PLP)
• B7 (Biotin)
• B9 (Folate)
• B12 (Cobalamin)

Question 509

Water soluble vitamins all wash out easily from body except _____.

Answer 509

B9 and B12

Question 510

B9 and B12 are stored in the _____.

Answer 510

liver (~3-4 years)

Question 511

B-complex deficiencies often result in _____.

Answer 511

• dermatitis
• glossitis
• diarrhea

Question 512

Vitamin A is also called _____.

Answer 512

Retinol

Question 513

_____ is an antioxidant; a constituent of visual pigments (retinal); essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells); prevents squamous metaplasia; used to treat measles and acute promyelocytic leukemia (APL).

Answer 513

Vitamin A

Question 514

Vitamin A is found in _____.

Answer 514

liver

leafy vegetables

Question 515

_____ is used to treat severe cystic acne.

Answer 515

oral isotretinoin

Question 516

_____ is used to treat acute promyelocytic leukemia.

Answer 516

all-trans retinoic acid

Question 517

_____ causes night blindness (nyctalopia), dry scaly skin (xerosis cutis), corneal degeneration (keratomalacia), Bitot spots (foamy appearance) on conjunctiva and immunosuppression.

Answer 517

Vitamin A Deficiency

Question 518

_____ causes nausea, vomiting, vertigo, and blurred vision.

Answer 518

Acute Vitamin A Toxicity

Question 519

_____ causes alopecia, dry skin (eg. scaliness), hepatic toxicity and enlargement, arthralgias, and pseudotumor cerebri.

Answer 519

Chronic Vitamin A Toxicity

Question 520

A ⊝ pregnancy test and two forms of contraception are required before isotretinoin (vitamin A derivative) is prescribed because it is _____.

Answer 520

teratogenic

(cleft palate, cardiac abnormalities)

Question 521

Vitamin B1 is also called _____.

Answer 521

Thiamine

Question 522

In thiamine pyrophosphate (TPP), vitamin B3 is a cofactor for several dehydrogenase enzyme reactions:

Answer 522

ATP

• α-ketoglutarate dehydrogenase (TCA cycle)
• Transketolase (HMP shunt)
• Pyruvate dehydrogenase (links glycolysis to TCA cycle)
• Branched-chain ketoacid dehydrogenase

Question 523

_____ causes impaired glucose breakdown → ATP depletion worsened by glucose infusion; highly aerobic tissues (eg. brain, heart) are affected first.

Answer 523

Vitamin B1 Deficiency

(Beriberi)

Ber1Ber1

Question 524

Diagnosis of Vitamin B1 Deficiency is made by _____ following vitamin B1 administration.

Answer 524

↑ in RBC transketolase activity

Question 525

_____ causes confusion, ophthalmoplegia, ataxia, confabulation, personality change, memory loss (permanent) and damage to medial dorsal
nucleus of thalamus and mammillary bodies.

Answer 525

Wernicke-Korsakoff Syndrome

Triad:

• confusion
• ophthalmoplegia
• ataxia

Question 526

In alcoholic or malnourished patients, give thiamine before dextrose to ↓ risk of precipitating _____.

Answer 526

Wernicke Encephalopathy

Question 527

_____ causes polyneuropathy and symmetrical
muscle wasting.

Answer 527

Dry beriberi

Question 528

_____ causes high-output cardiac failure (dilated cardiomyopathy), edema.

Answer 528

Wet Beriberi

Question 529

Vitamin B2 is also called _____.

Answer 529

Riboflavin

Question 530

_____ is a component of flavins FAD and FMN, used as cofactors in redox reactions, eg. the succinate dehydrogenase reaction in the TCA cycle.

Answer 530

Vitamin B2

FAD and FMN are derived from riboFlavin (B2 ≈ 2 ATP).

Question 531

_____ causes cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth), corneal vascularization.

Answer 531

Vitamin B2 Deficiency

The 2 C’s of B2:

• Cheilosis
• Corneal vascularization

Question 532

Vitamin B3 is also called _____.

Answer 532

Niacin

Question 533

_____ is a constituent of NAD⁺, NADP⁺ (used in redox reactions). Derived from tryptophan. Synthesis requires vitamins B2 and B6. Used to treat dyslipidemia; lowers levels of VLDL and raises levels of HDL.

Answer 533

Vitamin B3

NAD derived from Niacin (B3 ≈ 3 ATP).

Question 534

Synthesis of Vitamin B3 requires _____.

Answer 534

Vitamins B2 and B6

Question 535

Vitamin B3 is derived from _____.

Answer 535

Tryptophan

Question 536

_____ causes glossitis and severe deficiency leads to pellagra, which can also be caused by Hartnup disease, malignant carcinoid syndrome (↑ tryptophan metabolism), and isoniazid (↓ vitamin B6).

Answer 536

Vitamin B3 Deficiency

(Pellagra)

Question 537

Symptoms of Pellagra

Answer 537

The 3 D’s of B3:

• Diarrhea
• Dementia (also hallucinations)
• Dermatitis (C3/C4 dermatome circumferential “broad collar” rash [Casal necklace], hyperpigmentation of sunexposed limbs).

Question 538

_____ is an autosomal recessive disease which causes deficiency of neutral amino acid (eg. tryptophan) transporters in proximal renal tubular cells and on enterocytes → neutral aminoaciduria and ↓ absorption from the gut → ↓ tryptophan for conversion to niacin → pellagra-like symptoms. Treat with high protein diet and nicotinic acid.

Answer 538

Hartnup Disease

Question 539

_____ causes facial flushing (induced by prostaglandin, not histamine; can be avoided by taking aspirin), hyperglycemia, hyperuricemia.

Answer 539

Vitamin B3 Toxicity

(Podagra)

Question 540

Vitamin B5 is also called _____.

Answer 540

Pantothenic Acid

Question 541

_____ is an Eessential component of coenzyme A (CoA, a cofactor for acyl transfers) and fatty acid synthase.

Answer 541

Vitamin B5

Question 542

_____ causes dermatitis, enteritis, alopecia, adrenal insufficiency.

Answer 542

Vitamin B5 Deficiency

Question 543

Vitamin B6 is also called _____.

Answer 543

Pyridoxine

Question 544

_____ is converted to pyridoxal phosphate (PLP), a cofactor used in transamination (eg. ALT and AST), decarboxylation reactions, glycogen phosphorylase, synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including serotonin, epinephrine, norepinephrine (NE), dopamine, and GABA.

Answer 544

Vitamin B6

Question 545

_____ causes convulsions, hyperirritability, peripheral neuropathy (deficiency inducible by isoniazid and oral contraceptives), sideroblastic anemias (due to impaired hemoglobin synthesis and iron excess).

Answer 545

Vitamin B6 Deficiency

Question 546

Vitamin B7 is also called _____.

Answer 546

Biotin

Question 547

Vitamin B7 is a cofactor for carboxylation enzymes (which add a 1-carbon group):

Answer 547

• Pyruvate carboxylase: pyruvate (3C) → oxaloacetate (4C)
• Acetyl-CoA carboxylase: acetyl-CoA (2C) → malonyl-CoA (3C)
• Propionyl-CoA carboxylase: propionyl-CoA (3C) → methylmalonyl-CoA (4C)

Question 548

_____ presents with dermatitis, enteritis and alopecia. It is caused by antibiotic use or excessive ingestion of raw egg whites (avidin).

Answer 548

Vitamin B7 Deficiency

Question 549

Vitamin B9 is also called _____.

Answer 549

Folate

Question 550

_____ is converted to tetrahydrofolic acid (THF), a coenzyme for 1-carbon transfer/methylation reactions. Important for the synthesis of nitrogenous bases in DNA and RNA.

Answer 550

Vitamin B9

Question 551

Vitamin B9 is found in _____.

Answer 551

leafy green vegetables

Folate from Foliage

Question 552

Vitamin B9 is absorbed in the _____.

Answer 552

jejunum

Question 553

A small reserve pool of Vitamin B9 is stored primarily in the _____.

Answer 553

liver

Question 554

_____ causes macrocytic, megaloblastic anemia; hypersegmented polymorphonuclear cells (PMNs); glossitis; no neurologic symptoms. Labs: ↑ homocysteine, normal methylmalonic acid levels. Seen in alcoholism and pregnancy.

Answer 554

Vitamin B9 Deficiency

Question 555

Vitamin B9 Deficiency can be caused by drugs such as _____.

Answer 555

Phenytoin

Sulfonamides

Methotrexate

Question 556

Supplemental maternal folic acid is given at least _____ prior to conception and during early pregnancy to ↓ risk of neural tube defects.

Answer 556

1 month

Question 557

Vitamin B12 is also called _____.

Answer 557

Cobalamin

Question 558

_____ is a cofactor for methionine synthase (transfers CH₃ groups as methylcobalamin) and methylmalonyl CoA mutase. Important for DNA synthesis.

Answer 558

Vitamin B12

Question 559

Vitamin B12 is found in _____.

Answer 559

animal products

Question 560

Vitamin B12 is synthesized only by _____.

Answer 560

microorganisms

Question 561

Vitamin B12 has a very large reserve pool (several years) stored primarily in the _____.

Answer 561

liver

Question 562

_____ causes macrocytic, megaloblastic anemia; hypersegmented PMNs; paresthesias and subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) due to abnormal myelin. Associated with ↑ serum homocysteine and methylmalonic acid levels, along with 2° folate deficiency. Prolonged deficiency → irreversible nerve damage.

Answer 562

Vitamin B12 Deficiency

Question 563

Vitamin B12 Deficiency is caused by _____.

Answer 563

• malabsorption (eg. sprue, enteritis, Diphyllobothrium latum, achlorhydria, bacterial overgrowth, alcohol excess)
• lack of intrinsic factor (eg. pernicious anemia, gastric bypass surgery)
• absence of terminal ileum (surgical resection, eg. for Crohn disease)
• insufficient intake (eg. veganism)

Question 564

The presence of anti-intrinsic factor antibodies is diagnostic for _____.

Answer 564

Pernicious Anemia

Question 565

Folate supplementation can mask the hematologic symptoms of B12 deficiency, but not the _____.

Answer 565

neurologic symptoms

Question 566

Vitamin B6 and B12 Processes

Answer 566

Question 567

Vitamin C is also called _____.

Answer 567

ascorbic acid

Question 568

_____ is an antioxidant that also facilitates iron absorption by reducing it to Fe²⁺ state. Necessary for hydroxylation of proline and lysine in collagen synthesis. Necessary for dopamine β-hydroxylase, which converts dopamine to NE.

Answer 568

Vitamin C

Question 569

Vitamin C is found in _____.

Answer 569

fruits and vegetables

Question 570

_____ is an ancillary treatment for methemoglobinemia by reducing Fe³⁺ to Fe²⁺.

Answer 570

Vitamin C

Question 571

_____ causes swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, “corkscrew” hair and weakened immune response.

Answer 571

Vitamin C Deficiency

(Scurvy)

Vitamin C deficiency causes sCurvy due to a
Collagen synthesis defect.

Question 572

_____ causes nausea, vomiting, diarrhea, fatigue, calcium oxalate nephrolithiasis. Can ↑ iron toxicity in predisposed individuals by increasing dietary iron absorption (ie. can worsen hereditary hemochromatosis or transfusion-related iron overload).

Answer 572

Vitamin C Toxicity

Question 573

Vitamin D2 (ergocalciferol) comes from ingestion of _____.

Answer 573

• plants
• fungi
• yeasts

Question 574

Vitamin D3 (cholecalciferol) comes from _____.

Answer 574

• exposure of skin (stratum basale) to sun
• fish
• milk
• plants

Question 575

Vitamin D2 is also called _____.

Answer 575

Ergocalciferol

Question 576

Vitamin D3 is also called _____.

Answer 576

Cholecalciferol

Question 577

Vitamin D2 and D3 are converted to their stirage form _____ in the _____.

Answer 577

25-OH D3

liver

Question 578

Vitamin D2 and D3 are converted to their active form, _____, in the _____.

Answer 578

1,25-(OH)2 D3 (calcitriol)

kidney

Question 579

Functions of Vitamin D

Answer 579

• ↑ intestinal absorption of Ca²⁺ and PO₄³
• ↑ bone mineralization at low levels
• ↑ bone resorption at higher levels

Question 580

At low levels of Vitamin D, there is _____.

Answer 580

↑ bone mineralization

Question 581

At high levels of Vitamin D, there is _____.

Answer 581

↑ bone resorption

Question 582

Vitamin D Regulation

Answer 582

• ↑ PTH, ↓ Ca²⁺, ↓ PO₄^3– → ↑ 1,25-(OH)₂D3 production
• 1,25-(OH)₂D3 feedback inhibits its own production.
• ↑ PTH → ↑ Ca²⁺ reabsorption and ↓ PO₄^3– reabsorption in the kidney.

Question 583

Vitamin D Deficiency causes _____ in children (deformity, such as genu varum “bow legs”).

Answer 583

Rickets

Question 584

Vitamin D Deficiency causes _____ in adults (bone pain and muscle weakness).

Answer 584

Osteomalacia

Question 585

Vitamin D Deficiency causes _____.

Answer 585

• Rickets in children (deformity, such as genu varum “bow legs”)
• Osteomalacia in adults (bone pain and muscle weakness)
• Hypocalcemic Tetany

Question 586

Vitamin D Deficiency is caused by _____.

Answer 586

• malabsorption
• ↓ sun exposure
• poor diet
• chronic kidney disease

Question 587

Vitamin D Deficiency is exacerbated by _____.

Answer 587

• pigmented skin
• premature birth

Question 588

Oral Vitamin D is given to _____ infants.

Answer 588

breastfed

Question 589

_____ causes hypercalcemia, hypercalciuria, loss of appetite and stupor and is seen in granulomatous disease (↑ activation by epithelioid macrophages).

Answer 589

Vitamin D Toxicity

Question 590

Vitamin E includes _____.

Answer 590

• tocopherol
• tocotrienol

Question 591

_____ is an antioxidant (protects RBCs and membranes from free radical damage). High-dose supplementation may alter metabolism of vitamin K → enhanced anticoagulant effects of warfarin.

Answer 591

Vitamin E

Question 592

_____ causes hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demyelination.

Answer 592

Vitamin E Deficiency

Question 593

The neurologic presentation of _____ may appear similar to vitamin B12 deficiency, but without megaloblastic anemia, hypersegmented neutrophils or ↑ serum methylmalonic acid levels.

Answer 593

Vitamin E Deficiency

Question 594

Excess vitamin E ↑ risk of _____ in infants.

Answer 594

enterocolitis

Question 595

Vitamin K includes _____.

Answer 595

• phytomenadione
• phylloquinone
• phytonadione
• menaquinone

Question 596

_____ is activated by epoxide reductase to the reduced form, which is a cofactor for the γ-carboxylation of glutamic acid residues on various proteins required for blood clotting. Synthesized by intestinal flora.

Answer 596

Vitamin K

Question 597

Vitamin K is necessary for the maturation of_____.

Answer 597

• clotting factors II, VII, IX, X (1972)
• proteins C and S

Question 598

_____ inhibits vitamin K-dependent synthesis of clotting factors and proteins.

Answer 598

Warfarin

Question 599

_____ causes neonatal hemorrhage with ↑ PT and ↑ aPTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize _____). Can also occur after prolonged use of broad-spectrum antibiotics.

Answer 599

Vitamin K Deficiency

Question 600

_____ is not in breast milk therefore neonates are given _____ injection at birth to prevent hemorrhagic disease of the newborn.

Answer 600

Vitamin K

Question 601

_____ is a mineral essential for the activity of 100+ enzymes. Important in the formation of _____ (transcription factor motif).

Answer 601

Zinc

Zinc Fingers

Question 602

_____ causes delayed wound healing, suppressed immunity, hypogonadism, ↓ adult hair (axillary, facial, pubic), dysgeusia, anosmia, acrodermatitis enteropathica. May predispose to alcoholic cirrhosis.

Answer 602

Zinc Deficiency

Question 603

_____ is protein malnutrition resulting in skin lesions, edema due to ↓ plasma oncotic pressure, liver malfunction (fatty change due to ↓ apolipoprotein synthesis). Clinical picture is small child with swollen abdomen.

Answer 603

Kwashiorkor

Question 604

Kwashiorkor Findings

Answer 604

Kwashiorkor results from protein deficient MEALS:

• Malnutrition
• Edema
• Anemia
• Liver (fatty)
• Skin lesions (eg, hyperkeratosis, dyspigmentation)

Question 605

_____ is malnutrition not causing edema. Diet is deficient in calories but no nutrients are entirely absent.

Answer 605

Marasmus

Marasmus results in Muscle wasting.

Question 606

Ethanol Metabolism

Answer 606

Question 607

_____ inhibits alcohol dehydrogenase and is an antidote for overdoses of methanol or ethylene glycol.

Answer 607

Fomepizole

FOMEpizole = For Overdoses of Methanol or Ethylene glycol

Question 608

_____ inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover symptoms), discouraging drinking.

Answer 608

Disulfiram

Question 609

_____ is the limiting reagent in ethanol metabolism.

Answer 609

NAD⁺

Question 610

Alcohol dehydrogenase operates via _____.

Answer 610

zero-order kinetics

Question 611

Ethanol metabolism ↑ NADH/NAD⁺ ratio in
liver, causing:

Answer 611

• Pyruvate → lactate (lactic acidosis)
• Oxaloacetate → malate (prevents gluconeogenesis → fasting hypoglycemia)
• Dihydroxyacetone phosphate → glycerol-3‑phosphate (combines with fatty acids to make triglycerides → hepatosteatosis)

Question 612

_____ disfavors TCA production of NADH → ↑ utilization of acetyl-CoA for ketogenesis (→ ketoacidosis) and lipogenesis (→ hepatosteatosis).

Answer 612

↑ NADH/NAD⁺ ratio

Question 613

Metabolism Sites:

fatty acid oxidation (β-oxidation)

Answer 613

Mitochondria

Question 614

Metabolism Sites:

acetyl-CoA production

Answer 614

Mitochondria

Question 615

Metabolism Sites:

TCA cycle

Answer 615

Mitochondria

Question 616

Metabolism Sites:

oxidative phosphorylation

Answer 616

Mitochondria

Question 617

Metabolism Sites:

ketogenesis

Answer 617

Mitochondria

Question 618

Metabolism Sites:

glycolysis

Answer 618

Cytoplasm

Question 619

Metabolism Sites:

HMP shunt

Answer 619

Cytoplasm

Question 620

Metabolism Sites:

synthesis of steroids (SER)

Answer 620

Cytoplasm

Question 621

Metabolism Sites:

synthesis of proteins (ribosomes, RER)

Answer 621

Cytoplasm

Question 622

Metabolism Sites:

synthesis of fatty acids

Answer 622

Cytoplasm

Question 623

Metabolism Sites:

synthesis of cholesterol

Answer 623

Cytoplasm

Question 624

Metabolism Sites:

synthesis of nucleotides

Answer 624

Cytoplasm

Question 625

_____ are processes which occur in both the mitochondria and the cytoplasm.

Answer 625

HUGs take two (ie, both).

• Heme Synthesis
• Urea Cycle
• Gluconeogenesis.

Question 626

Enzymes:

catalyzes transfer of a phosphate group from a high energy molecule (usually ATP) to a substrate (eg. phosphofructo_____)

Answer 626

Kinase

Question 627

Enzymes:

adds inorganic phosphate onto substrate without using ATP (eg. glycogen _____)

Answer 627

Phosphorylase

Question 628

Enzymes:

removes phosphate group from substrate (eg. fructose-1,6-bis_____)

Answer 628

Phosphatase

Question 629

Enzymes:

catalyzes oxidation-reduction reactions (eg. pyruvate _____)

Answer 629

Dehydrogenase

Question 630

Enzymes:

adds hydroxyl group (−OH) onto substrate (eg. tyrosine _____)

Answer 630

Hydroxylase

Question 631

Enzymes:

transfers CO₂ groups with the help of biotin (eg. pyruvate _____)

Answer 631

Carboxylase

Question 632

Enzymes:

relocates a functional group within a molecule (eg. vitamin B12-dependent methylmalonyl-CoA _____)

Answer 632

Mutase

Question 633

Enzymes:

joins two molecules together using a source of energy (eg. ATP, acetyl CoA, nucleotide sugar)

Answer 633

Synthase/Synthetase

Question 634

Glycolysis:

Rate-Determining Enzyme

Answer 634

Phosphofructokinase-1 (PFK-1)

Question 635

Glycolysis:

Regulators

Answer 635

• AMP ⊕, fructose-2,6-bisphosphate ⊕
• ATP ⊝, citrate ⊝

Question 636

Gluconeogenesis:

Rate-Determining Enzyme

Answer 636

Fructose-1,6-bisphosphatase

Question 637

Gluconeogenesis:

Regulators

Answer 637

• Citrate ⊕
• AMP ⊝, fructose-2,6-bisphosphate ⊝

Question 638

TCA Cycle:

Rate-Determining Enzyme

Answer 638

Isocitrate Dehydrogenase

Question 639

TCA Cycle:

Regulators

Answer 639

• ADP ⊕
• ATP ⊝, NADH ⊝

Question 640

Glycogenesis:

Rate-Determining Enzyme

Answer 640

Glycogen Synthase

Question 641

Glycogenesis:

Regulators

Answer 641

• Glucose-6-phosphate ⊕, insulin ⊕, cortisol ⊕
• Epinephrine ⊝, glucagon ⊝

Question 642

Glycogenolysis:

Rate-Determining Enzyme

Answer 642

Glycogen Phosphorylase

Question 643

Glycogenolysis:

Regulators

Answer 643

• Epinephrine ⊕, glucagon ⊕, AMP ⊕
• Glucose-6-phosphate ⊝, insulin ⊝, ATP ⊝

Question 644

HMP Shunt:

Rate-Determining Enzyme

Answer 644

Glucose-6-Phosphate Dehydrogenase (G6PD)

Question 645

HMP Shunt:

Regulators

Answer 645

• NADP+ ⊕
• NADPH ⊝

Question 646

De novo Pyrimidine Synthesis:

Rate-Determining Enzyme

Answer 646

Carbamoyl Phosphate Synthetase II

Question 647

De novo Pyrimidine Synthesis:

Regulators

Answer 647

• ATP ⊕, PRPP ⊕
• UTP ⊝

Question 648

De novo Purine Synthesis:

Rate-Determining Enzyme

Answer 648

Glutamine-phosphoribosylpyrophosphate (PRPP) Amidotransferase

Question 649

De novo Purine Synthesis:

Regulators

Answer 649

AMP ⊝, inosine monophosphate (IMP) ⊝, GMP ⊝

Question 650

Urea Cycle:

Rate-Determining Enzyme

Answer 650

Carbamoyl Phosphate Synthetase I

Question 651

Urea Cycle:

Regulators

Answer 651

N-acetylglutamate ⊕

Question 652

Fatty Acid Synthesis:

Rate-Determining Enzyme

Answer 652

Acetyl-CoA carboxylase (ACC)

Question 653

Fatty Acid Synthesis:

Regulators

Answer 653

• Insulin ⊕, citrate ⊕
• Glucagon ⊝, palmitoyl-CoA ⊝

Question 654

Fatty Acid Oxidation:

Rate-Determining Enzyme

Answer 654

Carnitine Acyltransferase I

Question 655

Fatty Acid Oxidation:

Regulators

Answer 655

Malonyl-CoA ⊝

Question 656

Ketogenesis:

Rate-Determining Enzyme

Answer 656

HMG-CoA Synthase

Question 657

Cholesterol Synthesis:

Rate-Determining Enzyme

Answer 657

HMG-CoA Reductase

Question 658

Cholesterol Synthesis:

Regulators

Answer 658

• Insulin ⊕, thyroxine ⊕
• Glucagon ⊝, cholesterol ⊝

Question 659

Biochemical Pathways

Answer 659

Question 660

Aerobic metabolism of one glucose molecule produces _____ via malate-aspartate shuttle (heart and liver).

Answer 660

32 net ATP

Question 661

Aerobic metabolism of one glucose molecule produces _____ via glycerol-3-phosphate shuttle (muscle).

Answer 661

30 net ATP

Question 662

Anaerobic glycolysis produces _____ per glucose molecule.

Answer 662

2 net ATP

Question 663

_____ can be coupled to energetically unfavorable reactions.

Answer 663

ATP hydrolysis

Question 664

Arsenic causes glycolysis to produce _____.

Answer 664

zero net ATP

Question 665

Activated Carriers:

Phosphoryl groups

Answer 665

ATP

Question 666

Activated Carriers:

Electrons

Answer 666

NADH

NADPH

FADH₂

Question 667

Activated Carriers:

Acyl groups

Answer 667

CoA

lipoamide

Question 668

Activated Carriers:

CO₂

Answer 668

Biotin

Question 669

Activated Carriers:

1-carbon units

Answer 669

Tetrahydrofolates

Question 670

Activated Carriers:

CH₃ groups

Answer 670

S-adenosylmethionine (SAM)

Question 671

Activated Carriers:

Aldehydes

Answer 671

TPP

Question 672

Universal Electron Acceptors

Answer 672

• NAD⁺
• NADP⁺
• FAD⁺

Question 673

Nicotinamides from Vitamin B3

Answer 673

• NAD⁺
• NADP⁺

Question 674

Flavin Nucleotides from Vitamin B2

Answer 674

FAD+

Question 675

NAD⁺ is generally used in _____ processes to carry reducing equivalents away as NADH.

Answer 675

catabolic

Question 676

NADPH is used in _____ processes (eg, steroid and fatty acid synthesis) as a supply of reducing equivalents.

Answer 676

anabolic

Question 677

NADPH is a product of the _____.

Answer 677

HMP shunt

Question 678

NADPH is used in _____.

Answer 678

• Anabolic processes
• Respiratory burst
• Cytochrome P-450 system
• Glutathione reductase

Question 679

Phosphorylation of glucose to yield glucose-6-phosphate is catalyzed by _____ in the liver and _____ in other tissues.

Answer 679

Glucokinase - liver

Hexokinase - other tissues

Question 680

_____ sequesters glucose in tissues, where it is used even when glucose concentrations are low.

Answer 680

Hexokinase

Question 681

At high glucose concentrations, _____ helps to store glucose in liver.

Answer 681

Glucokinase

Question 682

Glucose Phosphorylation:

• found in most tissues except liver and pancreatic β cells
• Km - Lower (↑ affinity)
• Vmax - Lower (↓ capacity)
• not induced by insulin
• feedback is inhibited by glucose-6-phosphate

Answer 682

Hexokinase

Question 683

Glucose Phosphorylation:

• found in the liver and β cells of pancreas
• Km - Higher (↓ affinity)
• Vmax - Higher (↑ capacity)
• induced by insulin
• feedback is inhibited by glucose-6-phosphate

Answer 683

Glucokinase

Question 684

Net Glycolysis (cytoplasm)

Answer 684

Glucose + 2 P_i + 2 ADP + 2 NAD⁺ → 2 pyruvate + 2 ATP + 2 NADH + 2 H⁺ + 2 H2O

Question 685

Glycolysis Regulation:

Require ATP

Answer 685

Question 686

Glycolysis Regulation:

Produce ATP

Answer 686

Question 687

Regulation by Fructose-2,6-Bisphosphate

Answer 687

Question 688

_____ is a mitochondrial enzyme complex linking glycolysis and TCA cycle. Differentially regulated in fed/fasting states (active in fed state).

Answer 688

Pyruvate Dehydrogenase Complex

Question 689

Pyruvate Dehydrogenase Complex Reaction

Answer 689

pyruvate + NAD⁺ + CoA → acetyl-CoA + CO₂ + NADH

Question 690

The Pyruvate Dehydrogenase Complex contains 3 enzymes that require 5 cofactors:

Answer 690

The Lovely Co-enzymes For Nerds

1. Thiamine pyrophosphate (B1)
2. Lipoic acid
3. CoA (B5, pantothenic acid)
4. FAD (B2, riboflavin)
5. NAD⁺ (B3, niacin)

Question 691

The Pyruvate Dehydrogenase Complex is activated by:

Answer 691

• ↑ NAD+/NADH ratio
• ↑ ADP
• ↑ Ca2+

Question 692

_____ inhibits lipoic acid. _____ poisoning clinical findings: imagine a vampire (pigmentary skin changes, skin cancer), vomiting and having diarrhea, running away from a cutie (QT prolongation) with garlic breath.

Answer 692

Arsenic

Question 693

_____ is an X-linked disease that causes a buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT).

Answer 693

Pyruvate Dehydrogenase Complex Deficiency

Question 694

_____ causes neurologic defects, lactic acidosis, ↑ serum alanine starting in infancy.

Answer 694

Pyruvate Dehydrogenase Complex Deficiency

Question 695

Pyruvate Dehydrogenase Complex Deficiency is treated with _____.

Answer 695

↑ intake of ketogenic nutrients (eg, high fat content or ↑ lysine and leucine).

Question 696

Pyruvate Metabolism

Answer 696

1. Alanine aminotransferase (B6): alanine carries amino groups to the liver from muscle
2. Pyruvate carboxylase (biotin): oxaloacetate can replenish TCA cycle or be used in gluconeogenesis
3. Pyruvate dehydrogenase (B1, B2, B3, B5, lipoic acid): transition from glycolysis to the TCA cycle
4. Lactic acid dehydrogenase (B3): end of anaerobic glycolysis (major pathway in RBCs, WBCs, kidney medulla, lens, testes, and cornea)

Question 697

TCA Cycle (Krebs Cycle)

Answer 697

Pyruvate → acetyl-CoA produces 1 NADH, 1 CO₂

Citrate Is Krebs’ Starting Substrate For Making Oxaloacetate.

Question 698

The TCA cycle produces _____.

Answer 698

3 NADH, 1 FADH₂, 2 CO₂, 1 GTP per acetyl-CoA = 10 ATP/acetyl-CoA (2× everything per glucose)

Question 699

TCA Cycle reactions occur in the _____.

Answer 699

mitochondria

Question 700

α-ketoglutarate dehydrogenase complex requires the same cofactors as the pyruvate dehydrogenase complex:

Answer 700

B1, B2, B3, B5, lipoic acid

Question 701

Electron Transport Chain

Answer 701

Question 702

NADH electrons from glycolysis enter mitochondria via the _____.

Answer 702

• malate-aspartate shuttle
• glycerol-3- phosphate shuttle

Question 703

FADH₂ electrons are transferred to _____ (at a lower energy level than NADH)

Answer 703

Complex II

Question 704

The passage of electrons results in the formation of a proton gradient that, coupled to _____, drives the production of ATP.

Answer 704

Oxidative Phosphorylation

Question 705

ATP produced via ATP Sythase

Answer 705

1 NADH → 2.5 ATP

1 FADH₂ → 1.5 ATP

Question 706

_____ directly inhibit electron transport, causing a ↓ proton gradient and block of ATP synthesis.

Answer 706

Electron Transport Inhibitors

Question 707

Electron Transport Inhibitors:

Complex I

Answer 707

Rotenone

Rotenone: complex one inhibitor

Question 708

Electron Transport Inhibitors:

Complex III

Answer 708

Antimycin A

“An-3-mycin” A: complex 3 inhibitor.

Question 709

Electron Transport Inhibitors:

Complex IV

Answer 709

• Cyanide
• Carbon monoxide
• Azide

The -ides (4 letters) inhibit complex IV.

Question 710

_____ directly inhibit mitochondrial ATP synthase, causing an ↑ proton gradient. No ATP is produced because electron transport stops.

Answer 710

ATP Synthase Inhibitors

Question 711

Oligomycin is an _____ inhibitor.

Answer 711

ATP Synthase

Question 712

_____ ↑ permeability of membrane, causing a ↓ proton gradient and ↑ O2 consumption. ATP synthesis stops, but electron transport continues. Produces heat.

Answer 712

Uncoupling Agents

Question 713

Uncoupling Agents

Answer 713

• 2,4-Dinitrophenol (used illicitly for weight loss)
• Aspirin (fevers often occur after aspirin overdose)
• Thermogenin in brown fat (has more mitochondria than white fat)

Question 714

Gluconeogenesis:
Irreversible Enzymes

Answer 714

Pathway Produces Fresh Glucose

• Pyruvate Carboxylase
• Phosphoenolpyruvate Carboxykinase
• Fructose-1,6-bisphosphatase
• Glucose-6-phosphatase

Question 715

Gluconeogenesis:

• in mitochondria
• pyruvate → oxaloacetate
• requires biotin and ATP
• activated by acetyl-CoA

Answer 715

Pyruvate Carboxylase

Question 716

Gluconeogenesis:

• in cytosol
• oxaloacetate → phosphoenolpyruvate
• requires GTP

Answer 716

Phosphoenolpyruvate Carboxykinase

Question 717

Gluconeogenesis:

• in cytosol
• fructose-1,6-bisphosphate → fructose-6-phosphate
• citrate ⊕, AMP ⊝, fructose 2,6-bisphosphate ⊝

Answer 717

Fructose-1,6-bisphosphatase

Question 718

Gluconeogenesis:

• iIn ER
• glucose-6-phosphate → glucose

Answer 718

Glucose-6-phosphatase

Question 719

_____ occurs primarily in liver (also in the kidney and intestinal epithelium); serves to maintain euglycemia during fasting.

Answer 719

Gluconeogenesis

Question 720

Muscle cannot participate in gluconeogenesis because it lacks _____.

Answer 720

Glucose-6-phosphatase

Question 721

Odd-chain fatty acids yield _____ during metabolism, which can enter the TCA cycle (as succinyl-CoA), undergo gluconeogenesis, and serve as a glucose source.

Answer 721

1 propionyl-CoA

Question 722

Even-chain fatty acids cannot produce new glucose, since they yield only _____ equivalents.

Answer 722

acetyl-CoA

Question 723

_____ provides a source of NADPH from abundantly available glucose-6-P (NADPH is required for reductive reactions, eg, glutathione reduction inside RBCs, fatty acid and cholesterol biosynthesis).

Answer 723

HMP Shunt

(Pentose Phosphate Pathway)

Question 724

_____ yields ribose for nucleotide synthesis and has two distinct phases (oxidative and nonoxidative), both of which occur in the cytoplasm. No ATP is used or produced.

Answer 724

HMP Shunt

(Pentose Phosphate Pathway)

Question 725

The HMP Shunt is found in _____.

Answer 725

• lactating mammary glands
• liver
• adrenal cortex
• RBCs

*sites of fatty acid or steroid synthesis

Question 726

HMP Shunt

(Pentose Phosphate Pathway)

Answer 726

Question 727

_____ is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides.

Answer 727

NADPH

Question 728

In _____, ↓ NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents (eg, fava beans, sulfonamides, nitrofurantoin, primaquine/chloroquine, antituberculosis drugs). Infection (most common cause) can also precipitate hemolysis; inflammatory response produces free radicals that diffuse into RBCs, causing oxidative damage.

Answer 728

Glucose-6-Phosphate Dehydrogenase Deficiency

Question 729

_____ is an X-linked recessive disorder; most common human enzyme deficiency; more prevalent among African Americans. ↑ malarial resistance.

Answer 729

Glucose-6-Phosphate Dehydrogenase Deficiency

Question 730

Glucose-6-Phosphate Dehydrogenase

Answer 730

Question 731

_____ are denatured globin chains that precipitate within RBCs due to oxidative stress.

Answer 731

Heinz Bodies

Question 732

_____ result from the phagocytic removal of Heinz bodies by splenic macrophages.

Answer 732

Bite Cells

Bite into some Heinz ketchup.

Question 733

_____ is an autosomal recessive disease which involves a defect in fructokinase. It’s a benign, asymptomatic condition, since fructose is not trapped in cells. Hexokinase becomes 1° pathway for converting fructose to fructose-6-phosphate.

Answer 733

Essential Fructosuria

Question 734

_____ presents with fructose in the blood and urine. Disorders of fructose metabolism cause milder symptoms than analogous disorders of galactose metabolism.

Answer 734

Essential Fructosuria

Question 735

_____ is an autosomal recessive disease which causes a hereditary deficiency of aldolase B. Fructose-1-phosphate accumulates, causing a ↓ in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis. Hypoglycemia, jaundice, cirrhosis and vomiting present following consumption of fruit, juice, or honey. Urine dipstick will be ⊝ (tests for glucose only); reducing sugar can be detected in the urine (nonspecific test for inborn errors of carbohydrate metabolism).

Answer 735

Hereditary Fructose Intolerance

Fructose is to Aldolase B as Galactose is to UridylTransferase (FAB GUT).

Question 736

Hereditary Fructose Intolerance is treated with _____.

Answer 736

↓ intake of both fructose and sucrose (glucose + fructose)

Question 737

Fructose Metabolism

Answer 737

Question 738

_____ is an autosomal recessive condition where galactitol accumulates if galactose is present in diet. It is a relatively mild condition where galactose appears in blood (galactosemia) and urine (galactosuria). May present as infantile cataracts. failure to track objects or to develop a social smile.

Answer 738

Galactokinase Deficiency

Question 739

_____ is an autosomal recessive disease which causes the absence of galactose-1-phosphate uridyltransferase. Damage is caused by accumulation of toxic substances (including galactitol, which accumulates in the lens of the eye). Symptoms develop when infant begins feeding (lactose present in breast milk and routine formula) and include failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability.

Answer 739

Classic Galactosemia

Fructose is to Aldolase B as Galactose is to UridylTransferase (FAB GUT).

Question 740

Classic Galactosemia can predispose neonates to _____ sepsis.

Answer 740

E. coli

Question 741

Classic Galactosemia is treated with _____.

Answer 741

exclusion galactose and lactose (galactose + glucose) from diet

Question 742

Galactose Metabolism

Answer 742

Question 743

The more serious cases of galactosemia lead to _____.

Answer 743

PO₄³⁻ depletion

Question 744

An alternative method of trapping glucose in the cell is to convert it to its alcohol counterpart, _____, via aldose reductase.

Answer 744

Sorbitol

Question 745

Some tissues then convert sorbitol to fructose using _____; tissues with an insufficient amount/activity of this enzyme are at risk of intracellular sorbitol accumulation, causing osmotic damage (eg, cataracts, retinopathy, and peripheral neuropathy seen with chronic hyperglycemia in diabetes).

Answer 745

Sorbitol Dehydrogenase

Question 746

High blood levels of galactose also result in conversion to the osmotically active galactitol via _____.

Answer 746

Aldose Reductase

Question 747

_____ have both aldose reductase and sorbitol dehydrogenase.

Answer 747

They LOSe sorbitol.

• Liver
• Ovaries
• Seminal vesicles

Question 748

_____ has primarily aldose reductase while _____, _____, _____ have only aldose reductase.

Answer 748

LuRKS

• Lens
• Retina
• Kidneys
• Schwann cells

Question 749

Sorbitol Metabolism

Answer 749

Question 750

_____functions on the intestinal brush border to digest lactose (in milk and milk products) into glucose and galactose.

Answer 750

Lactase

Question 751

Lactase Deficiency:

• age-dependent decline after childhood (absence of lactase-persistent allele)
• common in people of Asian, African, or Native American descent

Answer 751

Primary Lactase deficiency

Question 752

Lactase Deficiency:

loss of intestinal brush border due to gastroenteritis (eg, rotavirus), autoimmune disease, etc.

Answer 752

Secondary Lactase Deficiency

Question 753

_____ presents with bloating, cramps, flatulence, and osmotic diarrhea. Stool demonstrates ↓ pH and breath shows ↑ hydrogen content with lactose hydrogen breath test. Intestinal biopsy reveals normal mucosa in patients with hereditary lactose intolerance.

Answer 753

Lactase Deficiency

Question 754

Lactase Deficiency is treated with _____.

Answer 754

• avoidance of dairy products
• lactase pills
• lactose-free milk

Question 755

Only _____ are found in proteins.

Answer 755

L-amino acids

Question 756

Essential Amino Acids

Answer 756

PVT TIM HaLL

• Phenylalanine
• Valine
• Tyrosine
• Threonine
• Isoleucine
• Methionine
• Histidine
• Leucine
• Lysine

Question 757

Glucogenic Amino Acids

Answer 757

I met his valentine, she is so sweet (glucogenic).

• Methionine
• Histidine
• Valine

Question 758

Glucogenic/Ketogenic Amino Acids

Answer 758

• Isoleucine
• Phenylalanine
• Threonine
• Tyrosine

Question 759

Ketogenic Amino Acids

Answer 759

The onLy pureLy ketogenic amino acids.

• Leucine
• Lysine

Question 760

Acidic amino acids (aspartic acid, glutamic acid) are _____ charged at body pH.

Answer 760

negatively charged

Question 761

Basic Amino Acids

Answer 761

His lys (lies) are basic.

• Histidine
• Lysine
• Arginine

Question 762

_____ is the most basic amino acid.

Answer 762

Arginine

Question 763

Histidine has _____ at body pH.

Answer 763

no charge

Question 764

_____ are amino acids required during periods of growth.

Answer 764

• Arginine
• Histidine

Question 765

_____ are ↑ in histones which bind negatively charged DNA.

Answer 765

• Arginine
• Lysine

Question 766

_____ results in the formation of common metabolites (eg, pyruvate, acetyl-CoA), which serve as metabolic fuels. Excess nitrogen generated by this process is converted to urea and excreted by the kidneys.

Answer 766

Amino Acid Catabolism

Question 767

Urea Cycle

Answer 767

Ordinarily, Careless Crappers Are Also Frivolous About Urination.

Question 768

Transport of Ammonia by Alanine

Answer 768

Question 769

_____ can be acquired (eg, liver disease) or hereditary (eg, urea cycle enzyme deficiencies). Excess NH₃ depletes glutamate (GABA) in the CNS and α-ketoglutarate → inhibition of TCA cycle. It is treated with protein limitation in the diet.

Answer 769

Hyperammonemia

Question 770

_____ may be given to ↓ ammonia levels.

Answer 770

• Lactulose to acidify the GI tract and trap NH₄⁺ for excretion.
• Antibiotics (eg, rifaximin, neomycin) to ↓ colonic ammoniagenic bacteria.
• Benzoate, phenylacetate, or phenylbutyrate react with glycine or glutamine, forming products that are renally excreted.

Question 771

_____ accumulation causes flapping tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision.

Answer 771

Ammonia

Question 772

_____ is the most common urea cycle disorder. X-linked recessive (vs other urea cycle enzyme deficiencies, which are autosomal recessive). Interferes with the body’s ability to eliminate ammonia. Often evident in the first few days of life, but may present later. Excess carbamoyl phosphate is converted to orotic acid (part of the pyrimidine synthesis pathway).

Answer 772

Ornithine Transcarbamylase Deficiency

Question 773

_____ presents with ↑ orotic acid in blood and urine, ↓ BUN, symptoms of hyperammonemia. No megaloblastic anemia (vs orotic aciduria).

Answer 773

Ornithine Transcarbamylase Deficiency

Question 774

Amino Acid Derivatives

Answer 774

Question 775

Catecholamine Synthesis/Tyrosine Catabolism

Answer 775

Question 776

_____ is due to ↓ phenylalanine hydroxylase or ↓ tetrahydrobiopterin (BH₄) cofactor (malignant PKU). Tyrosine becomes essential. ↑ phenylalanine → excess phenyl ketones in urine.

Answer 776

Phenylketonuria

Question 777

_____ is an autosomal recessive disease which causes intellectual disability, growth retardation, seizures, fair complexion, eczema, musty body odor.

Answer 777

Phenylketonuria

Question 778

Phenylketonuria is treated with _____.

Answer 778

• ↓ phenylalanine and ↑ tyrosine in diet
• tetrahydrobiopterin supplementation

Question 779

The incidence of phenylketonuria is _____.

Answer 779

1:10,000

Question 780

_____ - lack of proper dietary therapy during pregnancy. Findings in infant: microcephaly, intellectual disability, growth retardation, congenital heart defects.

Answer 780

Maternal PKU

Question 781

Phenylketonuria screening occurs _____ after birth (normal at birth because of maternal enzyme during fetal life).

Answer 781

2–3 days

Question 782

Phenyl Ketones

Answer 782

• Phenylacetate
• Phenyllactate
• Phenylpyruvate

Question 783

Phenylketonuria presents with musty body odor due to _____.

Answer 783

disorder of aromatic amino acid metabolism

Question 784

PKU patients must avoid the artificial sweetener _____, which contains phenylalanine.

Answer 784

Aspartame

Question 785

_____ is an autosomal recessive disease where there is blocked degradation of branched amino acids (Isoleucine, Leucine, Valine) due to ↓ branched-chain α-ketoacid dehydrogenase (B1). Causes ↑ α-ketoacids in the blood, especially those of leucine. Causes severe CNS defects, intellectual disability, and death.

Answer 785

Maple Syrup Urine Disease

I Love Vermont maple syrup from maple trees (with B1ranches).

Question 786

_____ presents with vomiting, poor feeding and urine that smells like maple syrup/burnt sugar.

Answer 786

Maple Syrup Urine Disease

Question 787

Maple Syrup Urine Disease is treated with _____.

Answer 787

• restriction of isoleucine, leucine, valine in diet
• thiamine supplementation.

Question 788

_____ is an autosomal recessive congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate → pigment-forming homogentisic acid accumulates in tissue. Usually benign.

Answer 788

Alkaptonuria

Question 789

_____ presents with bluish-black connective tissue, ear cartilage, and sclerae (ochronosis); urine turns black on prolonged exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage).

Answer 789

Alkaptonuria

Question 790

Homocystinuria Types

Answer 790

• Cystathionine synthase deficiency (treatment: ↓ methionine, ↑ cysteine, ↑ B6, B12, and folate in diet)
• ↓ affinity of cystathionine synthase for pyridoxal phosphate (treatment: ↑↑ B6 and ↑ cysteine in diet)
• Methionine synthase (homocysteine methyltransferase) deficiency (treatment: ↑ methionine in diet)

*all autosomal recessive

Question 791

Homocystinuria Findings

Answer 791

HOMOCYstinuria:

• ↑↑ Homocysteine in urine
• Osteoporosis
• Marfanoid habitus,
• Ocular changes (downward and inward lens subluxation)
• Cardiovascular effects (thrombosis and atherosclerosis → stroke and MI)
• kYphosis
• intellectual disability

Question 792

Homocysteine Metabolism

Answer 792

Question 793

_____ is an autosomal recessive hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of Cystine, Ornithine, Lysine, and Arginine Excess cystine in the urine can lead to recurrent precipitation of hexagonal cystine stones.

Answer 793

Cystinuria

COLA

• Cystine
• Ornithine
• Lysine
• Arginine

Question 794

The incidence of Cystinuria is _____.

Answer 794

1:7000

Question 795

_____ is diagnostic for Cystinuria.

Answer 795

Urinary Cyanide-Nitroprusside Test

Question 796

Cystinuria is treated with _____.

Answer 796

• urinary alkalinization (eg, potassium citrate, acetazolamide) and chelating agents (eg, penicillamine) ↑ solubility of cystine stones
• good hydration

Question 797

Cystine is made of 2 cysteines connected by a _____.

Answer 797

disulfide bond

Question 798

Glycogen Regulation by Insulin and Glucagon/Epinephrine

Answer 798

Question 799

Glycogen branches have _____.

Answer 799

α-(1,6) bonds

Question 800

Glycogen linkages have _____.

Answer 800

α-(1,4) bonds

Question 801

Glycogen Metabolism in Skeletal Muscle

Answer 801

Glycogen undergoes glycogenolysis → glucose-1-phosphate → glucose-6-phosphate, which is rapidly metabolized during exercise.

Question 802

Glycogen Metabolism in Hepatocytes

Answer 802

• Glycogen is stored and undergoes glycogenolysis to maintain blood sugar at appropriate levels.
• Glycogen phosphorylase ④ liberates glucose-1-phosphate residues off branched glycogen until 4 glucose units remain on a branch.
• Then 4-α-d glucanotransferase (debranching enzyme ⑤) moves 3 of the 4 glucose units from the branch to the linkage.
• Then α-1,6-glucosidase (debranching enzyme ⑥) cleaves off the last residue, liberating glucose.
• “Limit dextrin” refers to the one to four residues remaining on a branch after glycogen phosphorylase has already shortened it.

Question 803

At least 15 types of _____ have been identified, all resulting in abnormal glycogen metabolism and an accumulation of glycogen within cells.

Answer 803

Glycogen Storage Diseases

Question 804

_____ identifies glycogen and is useful in identifying glycogen storage diseases.

Answer 804

Periodic Acid–Schiff Stain

Question 805

Glycogen Storage Diseases

Answer 805

Very Poor Carbohydrate Metabolism

• Von Gierke disease (type I)
• Pompe disease (type II)
• Cori disease (type III)
• McArdle disease (type V)

*autosomal recessive.

Question 806

Glycogen Storage Diseases:

• severe fasting hypoglycemia
• ↑↑ glycogen in liver and kidneys
• ↑ blood lactate
• ↑ triglycerides
• ↑ uric acid (gout)
• hepatomegaly
• renomegaly
• liver does not regulate blood glucose

Answer 806

Von Gierke disease (type I)

Von Gierke = Glycogen, Gout

Question 807

Glycogen Storage Diseases:

deficient in Von Gierke disease (type I)

Answer 807

Glucose-6-phosphatase

Von Gierke = Glucose-6-phosphatase

Question 808

Glycogen Storage Diseases:

• oral glucose/cornstarch should be given frequently
• fructose and galactose should be avoided

Answer 808

Von Gierke disease (type I)

Question 809

Glycogen Storage Diseases:

impaired gluconeogenesis and glycogenolysis

Answer 809

Von Gierke disease (type I)

Question 810

Glycogen Storage Diseases:

• cardiomegaly
• hypertrophic
• cardiomyopathy
• hypotonia
• exercise intolerance
• systemic findings lead to early death

Answer 810

Pompe disease (type II)

Pompe trashes the Pump
(heart, liver, and muscle)

Question 811

Glycogen Storage Diseases:

deficient in Pompe disease (type II)

Answer 811

Lysosomal acid α-1,4-glucosidase with α-1,6-glucosidase activity (acid maltase)

PomPe trashes the PumP (1,4)

Question 812

Glycogen Storage Diseases:

• milder form of von Gierke (type I) with normal blood lactate levels
• accumulation of limit dextrin–like structures in cytosol

Answer 812

Cori disease (type III)

Question 813

Glycogen Storage Diseases:

deficient in Cori disease (type III)

Answer 813

Debranching enzyme (α-1,6-glucosidase)

Question 814

Glycogen Storage Diseases:

gluconeogenesis is intact

Answer 814

Cori disease (type III)

Question 815

Glycogen Storage Diseases:

• ↑ glycogen in muscle, but muscle cannot break it down → painful muscle cramps
• myoglobinuria (red urine) with strenuous exercise
• arrhythmia from electrolyte abnormalities
• second-wind phenomenon noted during exercise due to ↑ muscular blood flow

Answer 815

McArdle disease (type V)

McArdle = Muscle, Myoglobinuria

Question 816

Glycogen Storage Diseases:

• deficient in McArdle disease (type V)
• hallmark is a flat venous lactate curve with normal rise in ammonia levels during exercise

Answer 816

Skeletal muscle glycogen phosphorylase (Myophosphorylase)

McArdle = Myophosphorylase

Question 817

Glycogen Storage Diseases:

blood glucose levels typically unaffected

Answer 817

McArdle disease (type V)

Question 818

Lysosomal Storage Diseases

Answer 818

Sphingolipidoses

• Tay-Sachs disease
• Fabry disease
• Metachromatic Leukodystrophy
• Krabbe disease
• Niemann-Pick disease

Mucopolysaccharidoses

• Hurler syndrome
• Hunter syndrome

Question 819

Sphingolipidoses:

• autosomal recessive
• progressive neurodegeneration,
• developmental delay
• “cherry-red” spot on macula
• lysosomes with onion skin
• no hepatosplenomegaly (vs Niemann-Pick)

Answer 819

Tay-Sachs disease

Question 820

Sphingolipidoses:

deficient in Tay-Sachs disease

Answer 820

Hexosaminidase A ①

TAy-SaX = HeXosaminidase A

Question 821

Sphingolipidoses:

accumulates in Tay-Sachs disease

Answer 821

GM₂ ganglioside

Question 822

Sphingolipidoses:

• X-linked recessive
• Early: triad of episodic peripheral neuropathy, angiokeratomas, hypohidrosis
• Late: progressive renal failure, cardiovascular disease

Answer 822

Fabry disease

Question 823

Sphingolipidoses:

deficient in Fabry disease

Answer 823

α-galactosidase A ②

Question 824

Sphingolipidoses:

accumulates in Fabry disease

Answer 824

Ceramide Trihexoside

Question 825

Sphingolipidoses:

• autosomal recessive
• central and peripheral demyelination with ataxia
• dementia

Answer 825

Metachromatic Leukodystrophy

Question 826

Sphingolipidoses:

deficient in Metachromatic Leukodystrophy

Answer 826

Arylsulfatase A ③

Question 827

Sphingolipidoses:

accumulates in Metachromatic Leukodystrophy

Answer 827

Cerebroside Sulfate

Question 828

Sphingolipidoses:

• autosomal recessive
• peripheral neuropathy
• destruction of oligodendrocytes
• developmental delay
• optic atrophy
• globoid cells

Answer 828

Krabbe disease

Question 829

Sphingolipidoses:

deficient in Krabbe disease

Answer 829

Galactocerebrosidase ④

Question 830

Sphingolipidoses:

accumulates in Krabbe disease

Answer 830

• Galactocerebroside
• Psychosine

Question 831

Sphingolipidoses:

• autosomal recessive
• most common
• hepatosplenomegaly
• pancytopenia
• osteoporosis
• avascular necrosis of femur
• bone crises
• Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper)

Answer 831

Gaucher disease

Question 832

Sphingolipidoses:

deficient in Gaucher disease

Answer 832

Glucocerebrosidase (β-glucosidase) ⑤

Question 833

Sphingolipidoses:

accumulates in Gaucher disease

Answer 833

Glucocerebroside

Question 834

Sphingolipidoses:

• autosomal recessive
• progressive neurodegeneration
• hepatosplenomegaly
• foam cells (lipid-laden macrophages)
• “cherry-red” spot on macula

Answer 834

Niemann-Pick disease

Question 835

Sphingolipidoses:

deficient in Niemann-Pick disease

Answer 835

Sphingomyelinase ⑥

No man picks (Niemann-Pick) his nose with his sphinger (sphingomyelinase).

Question 836

Sphingolipidoses:

accumulates in Niemann-Pick disease

Answer 836

Sphingomyelin

No man picks (Niemann-Pick) his nose with his sphinger (sphingomyelin).

Question 837

Ther is ↑ incidence of Tay-Sachs, Niemann-Pick, and some forms of Gaucher disease in _____.

Answer 837

Ashkenazi Jews

Question 838

Mucopolysaccharidoses:

• autosomal recessive
• developmental delay
• gargoylism
• airway obstruction
• corneal clouding
• hepatosplenomegaly

Answer 838

Hurler syndrome

Question 839

Mucopolysaccharidoses:

deficient in Hurler syndrome

Answer 839

α-L-iduronidase

Question 840

Mucopolysaccharidoses:

accumulates in Hurler syndrome

Answer 840

• Heparan sulfate
• Dermatan sulfate

Question 841

Mucopolysaccharidoses:

• X-linked recessive
• mild Hurler + aggressive behavior
• no corneal clouding

Answer 841

Hunter syndrome

Hunters see clearly (no corneal clouding) and aggressively aim for the X (X-linked recessive).

Question 842

Mucopolysaccharidoses:

deficient in Hunter syndrome

Answer 842

Iduronate-2-sulfatase

Question 843

Mucopolysaccharidoses:

accumulates in Hunter syndrome

Answer 843

• Heparan sulfate
• Dermatan sulfate

Question 844

Fatty Acid Metabolism

Answer 844

Question 845

Fatty acid synthesis requires transport of _____ from mitochondria to cytosol.

Answer 845

Citrate

“SYtrate” = SYnthesis

Question 846

Fatty acid metabolism predominantly occurs in _____.

Answer 846

• liver
• lactating mammary glands
• adipose tissue

Question 847

Long-chain fatty acid (LCFA) degradation requires _____-dependent transport into the mitochondrial matrix.

Answer 847

Carnitine

CARnitine = CARnage of fatty acids

Question 848

_____ is an inherited defect in transport of LCFAs into the mitochondria → toxic accumulation. Causes weakness, hypotonia, and hypoketotic hypoglycemia.

Answer 848

Systemic 1° Carnitine Deficiency

Question 849

_____ causes ↓ ability to break down fatty acids into acetyl-CoA → accumulation of fatty acyl carnitines in the blood with hypoketotic hypoglycemia. Causes vomiting, lethargy, seizures, coma, liver dysfunction, hyperammonemia. Can lead to sudden death in infants or children. Treat by avoiding fasting.

Answer 849

Medium-Chain Acyl-CoA Dehydrogenase Deficiency

Question 850

Ketone Body Metabolism

Answer 850

Question 851

Ketone Bodies

Answer 851

• Acetone
• Acetoacetate
• β-hydroxybutyrate

Question 852

In the liver, fatty acids and amino acids are metabolized to _____ to be used in muscle and brain.

Answer 852

• Acetoacetate
• β-hydroxybutyrate

Question 853

In prolonged starvation and diabetic ketoacidosis, _____ is depleted for gluconeogenesis.

Answer 853

Oxaloacetate

Question 854

In alcoholism, excess NADH shunts oxaloacetate to _____.

Answer 854

Malate

Question 855

In prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis. In alcoholism, excess NADH shunts oxaloacetate to malate. Both processes cause a buildup of _____, which shunts glucose, amino acids, and FFAs toward the production of ketone bodies.

Answer 855

Acetyl-CoA

Question 856

Ketone bodies make the breath smell like _____.

Answer 856

Acetone (fruity odor)

Question 857

Urine test for ketones can detect _____, but not β-hydroxybutyrate.

Answer 857

Acetoacetate

Question 858

RBCs cannot utilize ketones; they strictly use _____.

Answer 858

glucose

Question 859

HMG-CoA lyase is used for _____.

Answer 859

ketone production

Question 860

HMG-CoA reductase is used for _____.

Answer 860

cholesterol synthesis

Question 861

Metabolic Fuel Use

Answer 861

1g carb/protein (eg, whey) = 4 kcal
1g alcohol = 7 kcal
1g fatty acid = 9 kcal

*# letters = # kcal

Question 862

During fasting and starvation, priorities are to _____.

Answer 862

• supply sufficient glucose to the brain and RBCs
• preserve protein

Question 863

Glycolysis and aerobic respiration occur during the _____.

Answer 863

Fed State (after a meal)

Question 864

During the fed state (after a meal), _____ stimulates storage of lipids, proteins, and glycogen.

Answer 864

Insulin

Question 865

Hepatic glycogenolysis (major), hepatic gluconeogenesis and adipose release of FFA (minor) occur during _____.

Answer 865

Fasting (between meals)

Question 866

During fasting (between meals), _____ stimulate use of fuel reserves.

Answer 866

• Glucagon
• Epinephrine

Question 867

During starvation (days 1–3), blood glucose levels aremaintained by:

Answer 867

• Hepatic glycogenolysis
• Adipose release of FFA
• Muscle and liver, which shift fuel use from glucose to FFA
• Hepatic gluconeogenesis from peripheral tissue lactate and alanine, and from adipose tissue glycerol and propionyl-CoA (from odd-chain FFA—the only triacylglycerol components that contribute to gluconeogenesis)

Question 868

During starvation (after day 3), _____ are used and _____ become the main source of energy for the brain. After these are depleted, vital protein degradation accelerates, leading to organ failure and death. Amount of excess stores determines survival time.

Answer 868

adipose stores

ketone bodies

Question 869

Glycogen reserves are depleted after _____ of starvation.

Answer 869

day 1

Question 870

RBCs lack _____ and therefore cannot use ketones.

Answer 870

mitochondria

Question 871

Energy Use in Starvation

Answer 871

Question 872

Lipid Transport

Answer 872

Question 873

_____ mediates transfer of cholesterol esters to other lipoprotein particles.

Answer 873

Cholesterol Ester Transfer Protein

Question 874

Lipid Transport

Answer 874

Question 875

Key Enzymes in Lipid Transport

Answer 875

• Hepatic Lipase
• Hormone-Sensitive Lipase
• Lecithin-Cholesterol Acyltransferase
• Lipoprotein Lipase
• Pancreatic Lipase

Question 876

Key Enzymes in Lipid Transport:

degrades TGs remaining in IDL

Answer 876

Hepatic Lipase

Question 877

Key Enzymes in Lipid Transport:

degrades TGs stored in adipocytes

Answer 877

Hormone-Sensitive Lipase

Question 878

Key Enzymes in Lipid Transport:

catalyzes esterification of 2⁄3 of plasma cholesterol

Answer 878

Lecithin-Cholesterol Acyltransferase

Question 879

Key Enzymes in Lipid Transport:

• degrades TGs circulating chylomicrons and VLDLs
• found on vascular endothelial surface

Answer 879

Lipoprotein Lipase

Question 880

Key Enzymes in Lipid Transport:

degrades dietary TGs in small intestine

Answer 880

Pancreatic Lipase

Question 881

Major Apolipoproteins

Answer 881

Question 882

Apolipoproteins:

mediates remnant uptake

Answer 882

E

Everything Except LDL

Question 883

Apolipoproteins:

activates LCAT

Answer 883

A-I

Activate

Question 884

Apolipoproteins:

lipoprotein lipase cofactor that catalyzes cleavage

Answer 884

C-II

Cofactor that Catalyzes Cleavage

Question 885

Apolipoproteins:

• mediates chylomicron secretion into lymphatics
• only on particles originating from the intestines

Answer 885

B-48

Question 886

Apolipoproteins:

• binds LDL receptor
• only on particles originating from the liver

Answer 886

B-100

Question 887

Lipoproteins are composed of varying proportions of _____.

Answer 887

• cholesterol
• TGs
• phospholipids

Question 888

_____ carry the most cholesterol.

Answer 888

LDL, HDL

Question 889

_____ transports cholesterol from liver to tissues.

Answer 889

LDL

Question 890

_____ transports cholesterol from periphery to liver.

Answer 890

HDL

Question 891

_____ is needed to maintain cell membrane integrity and synthesize bile acid, steroids, and vitamin D.

Answer 891

Cholesterol

Question 892

_____ deliver dietary TGs to peripheral tissues. The also deliver cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their TGs. They are secreted by intestinal epithelial cells.

Answer 892

Chylomicrons

Question 893

_____ delivers hepatic TGs to peripheral tissue. It is secreted by liver.

Answer 893

VLDL

Question 894

_____ is formed in the degradation of VLDL. It delivers TGs and cholesterol to liver.

Answer 894

IDL

Question 895

_____ delivers hepatic cholesterol to peripheral tissues. It is formed by hepatic lipase modification of IDL in the liver and peripheral tissue. It is taken up by target cells via receptor-mediated endocytosis.

Answer 895

LDL

Question 896

_____ mediates reverse cholesterol transport from periphery to liver. It acts as a repository for apolipoproteins C and E (which are needed for chylomicron and VLDL metabolism). It is secreted from both liver and intestine. Alcohol ↑ synthesis.

Answer 896

HDL

Question 897

_____ is an autosomal recessive disease where chylomicrons, VLDL, and LDL are absent. There is a deficiency in ApoB-48, ApoB-100. Affected infants present with severe fat malabsorption, steatorrhea, and failure to thrive. Later manifestations include retinitis pigmentosa, spinocerebellar degeneration due to vitamin E deficiency, progressive ataxia, and acanthocytosis.

Answer 897

Abetalipoproteinemia

Question 898

Abetalipoproteinemia is treated with _____.

Answer 898

• restriction of long-chain fatty acids
• large doses of oral vitamin E

Question 899

Familial Dyslipidemias

Answer 899

• I—Hyperchylomicronemia
• II—Familial hypercholesterolemia
• III—Dysbetalipoproteinemia
• IV—Hypertriglyceridemia

Question 900

Familial Dyslipidemias:

• autosomal recessive
• lipoprotein lipase or apolipoprotein C-II deficiency

Answer 900

I—Hyperchylomicronemia

Question 901

Familial Dyslipidemias:

↑ chylomicrons, TG, and cholesterol

Answer 901

I—Hyperchylomicronemia

Question 902

Familial Dyslipidemias:

• pancreatitis
• hepatosplenomegaly
• eruptive/pruritic xanthomas
• no ↑ risk for atherosclerosis
• creamy layer in supernatant

Answer 902

I—Hyperchylomicronemia

Question 903

Familial Dyslipidemias:

• autosomal dominant
• absent or defective LDL receptors
• defective ApoB-100

Answer 903

II—Familial hypercholesterolemia

Question 904

Familial Dyslipidemias:

↑ LDL, cholesterol, and VLDL

Answer 904

II—Familial hypercholesterolemia

IIa: LDL, cholesterol
IIb: LDL, cholesterol, VLDL

Question 905

Familial Dyslipidemias:

• heterozygotes (1:500) have cholesterol ≈ 300mg/dL
• homozygotes (very rare) have cholesterol ≈ 700+ mg/dL.
• accelerated atherosclerosis (may
  have MI before age 20)
• tendon (Achilles) xanthomas
• corneal arcus

Answer 905

II—Familial hypercholesterolemia

Question 906

Familial Dyslipidemias:

• autosomal recessive
• defective ApoE

Answer 906

III—Dysbetalipoproteinemia

Question 907

Familial Dyslipidemias:

↑ chylomicrons and VLDL

Answer 907

III—Dysbetalipoproteinemia

Question 908

Familial Dyslipidemias:

• premature atherosclerosis
• tuberoeruptive xanthomas
• palmar xanthomas

Answer 908

III—Dysbetalipoproteinemia

Question 909

Familial Dyslipidemias:

• autosomal dominant
• hepatic overproduction of VLDL

Answer 909

IV—Hypertriglyceridemia

Question 910

Familial Dyslipidemias:

↑ VLD and TG

Answer 910

IV—Hypertriglyceridemia

Question 911

Familial Dyslipidemias:

• hypertriglyceridemia (> 1000 mg/dL) can cause acute pancreatitis
• related to insulin resistance

Answer 911

IV—Hypertriglyceridemia