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FirstAID > Biochemistry > Flashcards

Biochemistry Flashcards

1
Q

What gives DNA its (-) charge?

A

Phosphate groups

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2
Q

What gives histones their (+) charge?

A

Lysine and Arginine (what the octamer subunits primarily consist of)

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3
Q

What histones make up the nucleosome core in the “bead” on a string of chromatin? What histone ties the nucleosome “beads” together in a string?

A

Nucleosome core histones: H2A, H2B, H3, H4

H1 is the only histone that’s not in the nucleosome core; it ties the nucleosome core/beads together in a “string”

*referring to chromatin here (chromatin is the condensed form of DNA that allows it to fit into the nucleus)

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4
Q

Heterochromatin vs Euchromatin

A

Heterochromatin: highly condensed, transcriptionally inactive, sterically inaccessible

Euchromatin: less condensed, transcriptionally active, sterically accessible

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5
Q

How to mismatch repair enzymes distinguish between old and new strands?

A

Because template strand cytosine and adenine are methylated in DNA replication; this allows mismatch repair enzymes distinguish between old and new strands

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6
Q

What does hypermethylation do to DNA transcription?

A

inactivates transcription of DNA (“methylation makes DNA mute”)

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7
Q

What does histone acetylation do?

A

Relaxes DNA coiling, allowing for transcripiton (“acetylation makes DNA active”)

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8
Q

List the Purines. How many rings?

A

PURe As Gold: Adenine and Guanine

Have 2 rings

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9
Q

List the Pyrimidines. How many rings?

A

CUT the PY: Cytosine, Uracil, Thymine

Have 1 ring

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10
Q

RNA vs DNA nucleotides?

A

Uracil in RNA

Thymine in DNA

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11
Q

Which nucleotide has a ketone?
Which has a methyl?
Which makes uracil when deaminated?

A

Guanine has a ketone
Thymine has a methyl
Deamination of cytosine makes uracil

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12
Q

G-C vs A-T bonds:

A

G-C –> have 3 H-bonds, stronger than A-T bonds, which have 2 H-bonds

the more G-C content, the higher the melting point

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13
Q

Nucleoside vs Nucleotide

A 
Nucleoside = base + ribose (sugar)
Nucleotide = base + ribose + phosphate; linked by 3'-5' phosphodiester bond
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14
Q

Which amino acids are necessary for purine synthesis?

A

Glycine
Aspartate
Glutamine

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15
Q

Ribonucleotide Reductase

A

Convert ribonucleotides to deoxyribonucleotides in de novo pyrimidine synthesis (UDP –> dUDP)

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16
Q

Purine synthesis

A

1) Start with sugar + phosphate (PRPP)

2) Add base

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17
Q

Pyrimidine synthesis

A

1) Make temporary base (orotic acid)
2) Add sugar + phosphate (PRPP)
3) Modify base

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18
Q

Rate limiting enzyme in Purine synthesis?

A

Glutamine-PRPP-Amidotransferase (catalyzes step from PRPP –> –> –> IMP)

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19
Q

Rate limiting enzyme in Pyrimidine synthesis?

A

CPS - 2 = carbamoyl phosphate synthetase 2 (catalyzes step from ATP + CO2 + Glutamine –> Carbamoyl Phosphate)

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20
Q

Hydroxyurea mechanism

A

anti-cancer drug; inhibits ribonucleotide reductase (UDP–>dUDP)

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21
Q

6-mercaptopurine mechanism

A

blocks de-novo purine synthesis by blocking PRPP synthetase (Ribose-5-P –> PRPP)

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22
Q

5-Fluorouracil mechanism

A

Inhibits thymidylate synthase (dUMP –> dTMP)

get decreased dTMP

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23
Q

Methotrexate mechanism

A

inhibits dihydrofolate reductase (DHF–>THF); [thymidylate synthase uses THF (tetrahydrofolate), the active form of folic acid, to convert dUMP–>dTMP]
(get decreased dTMP)

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24
Q

Trimethoprim mechanism

A

inhibits bacterial dihydrofolate reductase (get decreased dTMP)

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25
Q

Mycophenylate mechanism

A

inhibits IMP (inosine monophosphate) dehydrogenase (IMP–>GMP)

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26
Q

How would a folic acid deficiency affect pyrimidine synthesis?

A

Thymidylate synthase (converts dUMP –> dTMP) uses THF, which is the active form of folic acid. So, without it, get decreased dTMP.

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27
Q

increased orotic acid in urine, megaloblastic anemia (that does not improve with vitamin B12 or folic acid), FTT; no hyperammonemia

A

Orotic aciduria (inability to convert orotic acid to UMP in the de novo pyrimidine synthesis pathway; d/t defect in either orotic acid phosphoribosyltransferase or orotidine-5’-phosphate decarboxylase)

  • Autosomal recessive
  • treat with oral uridine administration
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28
Q

What is the cause of orotic aciduria?

A

can’t convert orotic acid to UMP in the de novo pyrimidine synthesis pathway; due to a defect in either orotic acid phosphoribosyltransferase or orotidine 5’-phosphate decarboxylase
-Autosomal recessive

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29
Q

Adenosine Deaminase Deficinecy

A

Results in SCID (severe combined immunodeficiency disease)
can’t convert adenosine–>inosine in the purine salvage pathway, so get excess ATP and dATP, and thus feedback inhibition of ribonucleotide reductase (which imbalances the nucleotide pool); so prevents DNA synthesis and thus decreases the lymphocyte count

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30
Q

Absence of HGPRT

A

Lesch-Nyhan syndrome

  • HGPRT converts hypoxanthine to IMP and guanine to GMP; without it, have defective purine salvage. Get excess uric acid production and de novo purine synthesis (so increased PRPP amidotransferase activity)
  • X-linked recessive
  • Findings: retardation, self-mutilation (lip-biting), aggression, hyperuricemia, gout, choreoathetosis
  • Trtmnt: allopurinol (can’t treat CNS symptoms)
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31
Q

Allopurinol mechanism

A

inhibits xanthine oxidase (converts xanthine –> uric acid)

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32
Q

Origin of Replication

A

sequence of genome where DNA replication begins; single in prokaryotes, multiple in eukaryotes

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33
Q

Helicase

A

unwinds DNA template at replication fork

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34
Q

SSBPs (single-stranded binding proteins)

A

prevent strands from reannealing (stabilize unwound DNA)

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35
Q

Fluoroquinolones mechanism?

A

inhibit DNA gyrase (prokaryotic topoisomerase II)

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36
Q

Etoposide mechanism?

A

Inhibits human tropoisomerase (anti-cancer drug)

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37
Q

DNA topoisomerases

A

create a nick in the helix to relieve supercoils created during replication

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38
Q

DNA polymerase III

A
  • Prokaryotic only
  • Elongates leading strand by adding deoxynucleotides to the 3’ end.
  • Elongates lagging strand until it reaches the primer of the preceding fragment
  • 3’–>5’ exonuclease activity “proofreads” each added nucleotide.
  • SO: 5’–>3’ synthesis; 3’–>5’ proofreading exonuclease
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39
Q

DNA polymerase I

A

Prokaryotic only

  • Degrades RNA primer and fills in the gap with DNA (excision repair)
  • SO:excises RNA primer with 5’–>3’ exonuclease
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40
Q

Telomerase

A

adds DNA to 3’ ends of chromosomes to avoid loss of genetic material with each duplication

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41
Q

anti-topoisomerase antibody

A

anti-SCL70 - in diffuse scleroderma

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42
Q

Nucleotide Excision Repair

A
  • repair for small areas of damage
  • mutated in xeroderma pigmentosum (can’t repair thymine dimers after UV light exposure)
  • thymine dimers from UV light are usually repaired by NER
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43
Q

Base Excision Repair

A

-repair 1 damaged base

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44
Q

Mismatch Repair

A

unmethylated, newly synthesized string is recognized, mismatched nucleotides removed, and gap is filled and reasealed
-mutated in HNPCC (hereditary nonpolyposis colorectal cancer)

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45
Q

Nonhomologous end joining (type of double strand repair)

A
  • mutated in ataxia telangiectasia

- brings together 2 ends of DNA fragments

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46
Q
  • most abundant type of RNA?
  • longest type?
  • smallest type?
A

“rampant, massive, tiny”
rRNA = most abundant
mRNA = longest
tRNA = smallest

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47
Q

mRNA stop codons

A
  • UGA (u go away)
  • UAA (u are away)
  • UAG (u are gone)
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48
Q

Promoter

A

site where RNA polymerase and other transciption factors bind to DNA
-located 25 (TATA or Hogness box) or 70 (CAAT box) bases upstream from their genes

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49
Q

Enhancers and Silencers

A

Enhancers = stretch of DNA that binds transcription factors
Silencers = where negative regulators (repressors) bind
*Both can be located anywhere upstream, downstream, or even within transcribed gene

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50
Q

Eukaryotic RNA Polymerases I, II, III

A

RNA pol I: makes rRNA
RNA pol II: makes mRNA
RNA pol III: makes tRNA

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51
Q

Prokaryotic RNA polymerase

A

only 1 RNA polymerase –> makes all 3 kinds of RNA

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52
Q

Rifampin inhibits?

A

inhibits prokaryotic RNA polymerase

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53
Q

Where are rRNA, mRNA, tRNA synthesized?

A

rRNA –> synthesized in nucleolus

mRNA and tRNA –> synthesized in nucleoplasm

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54
Q

After transcription, processing of the pre-mRNA in the nucleus:

A

1) Capping on 5’-end
2) Polyadenylation on 3’ end (poly-A tail)
3) splicing out of introns by the spliceosome (so, introns stay in nucleus, exons leave nucleus, form mRNA)

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55
Q

antibodies to spliceosomal snRNPs?

A

Lupus pts

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56
Q

Effect of glucose on the lac operon?

A

in presence of glucose: glucose inhibits cAMP, so get decreased cAMP –> decreased CAP (activator protei) –> inhibition of lac operon
So:
-if have glucose –> lac operon is off
-if not lactose –> lac operon is off
-if no glucose, but have lactose –> lac operon is ON!

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57
Q

Aminoacyl-tRNA synthetase: what does it do and where does it act?

A

works at the 3’-OH-end of the tRNA; charges the amino acid onto the tRNA molecule
-uses ATP

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58
Q

Tetracyclines mechanism

A

Tetracyclines bind 30S subunit, preventing attachment of aminoacyl-tRNA

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59
Q

Steps of Elongation in protein synthesis:

A

1) aminoacyl-tRNA binds A site
2) ribosomal rRNA (“ribozyme” = peptidyl transferase) catalyzes peptide bond formation; transfers growing polypeptide to amino acid in A site
3) Ribosome advance 3 nucleotides toward 3’ end of RNA, moving peptidyl RNA to P site (translocation)

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

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60
Q

Aminoglycosides mechansim:

A

bind 30S on prokaryotic ribosome, and inhibit formation of the initiation complex and cause misreading of mRNA

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61
Q

Chloramphenicol mechanism

A

inhibits 50S peptidyltransferase

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62
Q

Macrolides mechanism

A

act on 50S subunit and block translocation (step 3 of elongation factor)

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63
Q

Clindamycin and Chloramphenicol mechanism

A

act at 50S; block peptide bond formation

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64
Q

Regulation of cell cycle by:

  • Cyclic-dependent kinases
  • Cyclins
  • Cylcin-CDK complexes
  • Rb and p53 (tumor suppressors)
A
  • CDKs = cyclin-dependent kinases: constitutive and inactive; expressed constantly, but inactive unless activated
  • Cyclins = activate CDKs
  • Cyclin-CDK complexes: must be both activated and inactivated for cell cycle to progress
  • Rb and p53: inhibit G1–>S progression; p53 also inhibits G2–>Mitosis
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65
Q

Which cell types are “permanent”, remaining in G0, regenerating from stem cells?

A

neurons, skeletal and cardiac muscles, RBCs

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66
Q

Which cell types are stable/quiescent –> enter G1 from G0 when stimulated?

A

hepatocytes, lymphocytes

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67
Q

Which cell types are labile –> never go to G0, divide rapidly with a short G1?

A

bone marrow, gut epithelium, skin, hair follicles (this type are most susceptible to cancer drugs)

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68
Q

Nissl bodies

A

RER in neurons (in dendrites; not in axons) –> synthesize enzymes and peptide neurotransmitters

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69
Q

What types of cells are rich in RER?

A

mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells

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70
Q

What types of cells are rich in SER?

A

liver hepatocytes (for drug and poison detox) and steroid-hormone producing cells of the adrenal cortex

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71
Q

Which amino acids are modified by the golgi?

A
  • Asparagine
  • Serine
  • Threonine
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72
Q

Failure to add mannose-6-phosphate to lysosome proteins results in what disease?

A

I-cell disease = Inclusion cell disease;
inherited lysosomal storage disease. Since not tagged by mannose-6-phosphate, enzymes are secreted outside the cell instead of to the lysosome.
-Features: coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes; often fatal in childhood

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73
Q

Peroxisome function

A

catabolism (breakdown) of very long fatty acids and amino acids

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74
Q

Proteasome function

A

barrel-shaped; degrades damaged or unnecessary proteins tagged for destruction with ubiquitin

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75
Q

Dynein and Kinesin

A

microtubule proteins:

  • dynein: retrogradeto microtubule (+ to -)
  • kinesin: anterograde to microtubule (- to +)
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76
Q

Immune disease due to a defect in microtubule polymerization?

A

Chediak-Higashi syndrome: microtubule polymerization defect resulting in decreased fusion of phagolysosomes and lysosomes; get recurrent pyogenic infections, partial albinism, peripheral nueropathy

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77
Q

Drugs that act on microtubules

A

1) -Bendazoles (anti-helminthic)
2) Griseofulvin (anti-fungal)
3) Vincristine/Vinblastine (anti-cancer) - block polymerization of microtubules
4) Paclitaxel (anti-breast cancer) - stabilizes microtubules
5) Colchicine (anti-gout)

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78
Q

Kartagener’s syndrome: cause, presentation

A
  • immotile cilia due to a dynein arm defect
  • Presentation:
  • infertility (male and female)
  • bronchiectasis
  • recurrent sinusitis (because can’t push bacteria/particles out)
  • situs inversus
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79
Q

Cytoskeletal elements

A
  • actin and myosin
  • microtubule (for movement)
  • intermediate filaments (for structure: vimentin, desmin, cytokeratin, lamins, GFAP, neurofilaments)
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80
Q

Contents of the plasma membrane

A
  • 50% cholesterol
  • 50% phospholipids (phosphatidylcholine, lecithin, phosphatidyl inositol)
  • also: sphingolipids, glycolipids, proteins
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81
Q

Stains for intermediate filaments: What types of cells do these stains stain?

  • Vimentin
  • Desmin
  • Cytokeratin
  • GFAP (glial fibrilary acid proteins)
  • Neurofilaments
A
  • Vimentin–>Connective tissue (so use for sarcomas, some carcinomas)
  • Desmin –> muscle (rhabdomyosarcoma, leiomyosarcoma)
  • cytokeratin–> epithelial cells (carcinomas, some sarcomas)
  • GFAP –> neuroglia
  • Neurofilaments –> neurons (adrenal neuroblastoma,primitive neuroectoderm tumors)
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82
Q

Oubain mechanism

A

inhibits the Na/K-ATPase by binding to the K site

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83
Q

Cardiac glycosides (digoxin, digotoxin) mechanism:

A

inhibit Na/K-ATPase, leading to indirect inhibition of Na/Ca-exchange; resulting in increased intracellular Ca and thus increased cardiac contractility

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84
Q

What are the 4 types of collagen?

A

“Strong, Slippery, Bloody BM!”
Type I: (90%) = Strong –> bone, skin, tendon, dentin, fascia, cornea, late wound repair
Type II: Slippery –> Cartilage (including hyaline)
Type III: Bloody –> skin, blood vessels, uterus, fetal tissue, granulation tissue (early wound healing)
Type IV: BM –> basement membrane and basal lamina

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85
Q

Collagen synthesis steps:

A

–Within Fibroblasts–

1) Synthesis in RER: Preprocollagen: Gly-X-Y polypeptide (X and Y are proline or lysine)
2) Hydorxylation of proline and lysine in ER: requires Vitamin C
3) Glycosylation in ER: formation of procollagen
4) Exocytosis of procollagen into extracellular space

–outside fibroblasts–

5) Proteolytic processing: procollagen is cleaved to become tropocollagen
6) Cross-linking: Collagen fibrils are formed by cross-linking tropocollagen molecules

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86
Q

Osteogenesis imperfecta:

-what type of collagen is defective?

A

=”brittle bone disease”

  • Autosomal dominant, abnormal type 1 collagen (type 2 is fatal in-utero)
  • defect is in the glycosylation phase (step 3) of collagen synthesis; can’t form triple helix (procollagen) from the pro-alpha-chain
  • Symptoms:
  • multiple fractures (may be during birth; may look like child abuse)
  • blue sclerae
  • hearing loss
  • dental problems due to lack of dentin
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87
Q

Blue Sclerae?

A

Osteogenesis imperfecta

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88
Q

Defect in Type III collagen?

A

Ehlers-Danlos syndrome (defect is ouside fibroblasts, can’t crosslink tropocollagen to make collagen fibrils)

  • “bloody” collagen defect (can be other types, but type III is most common)
  • hyperextensible skin
  • tendency to bleed (easy brusing, berry aneurysms, organ rupture)
  • hypermobile joints (joint dislocation)
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89
Q

Type IV collagen defect

A

Alport syndrome –> “can’t see, can’t pee, can’t hear”

  • usually X-linked recessive
  • progressive hereditary nephritis and deafness; may have ocular disturbances too.
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90
Q

Which two amino acids is elastin rich in?

A

glycine and proline

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91
Q

alpha-1-antitrypsin, elastase, elastin… relationship?

What if alpha-1-antitrypsin is deficient?

A

Elastin is broken down by elastase.
alpha-1-antitrypsin inhibits elastase, so inhibits elastin breakdown.
in alpha-1-antitrypsin deficiency: can’t inhibit elastase, so get excessive elastase activity and excessive elastin breakdown (can result in panacinal emphysema)

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92
Q

Blotting procedures: Southern, Northern, Western, Southwestern

A

“SNoW DRoP”
Southern Blot –> DNA sample; DNA probe
Northern Blot –> RNA sample; DNA probe
Western Blot –> Protein sample; antibody probe
Southwestern Blot –> identifies DNA-binding proteins, like transcription factors,using labeled oligonucleotide probes

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93
Q

sensitivity and specificity of ELISA (enzyme-linked immunosorbent assay)? how does it work/what does it test?

A

ELISA tests antigen-antibody reactivity; probe pt’s blood sample with either:

  • test antigen –> to see if immune system recognizes it/if antibody is there
  • test antibody –> to see if a certain antigen is there
  • solution has a color reaction if positive
  • sensitivity and specificity both close to 100%
  • Ex of how it works:
    1) put antigen to a virus in tube
    2) add pt’s serum (so, if pt has antibodies to virus, antibodies will bind virus antigens); rinse tube to get rid of unbound antibodies
    3) add anti-human Ig that is also connected to an enzyme; these anti-human antibodies will bind the antibody-antigen complexes
    4) add a substrate that will cause a color change of the enzyme, it it’s bound
  • Voila!*
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94
Q

Variable expression

A

severity of phenotype varies from 1 person to another (ie neurofibromatosis type 1, tuberous sclerosis –> may have varying severity)

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95
Q

Incomplete penetrance

A

not all individuals with mutant genotype show mutant phenotype

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96
Q

Pleiotropy

A

1 gene has >1 effect on an individual’s phenotype (ie PKU–> lots of seemingly unrelated symptoms)

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97
Q

Imprinting

A

differences in phenotype depend on whether mutation is maternal or paternal origin; occurs due to DNA methylation (ie Prader-Willi and Angelman’s syndromes)

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98
Q

Loss of heterozygosity

A

if a patient inherits or develops a mutation in a tumor suppressor gene, the complementary all has to be deleted/mutated before cancer develops (Retinoblastoma)

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99
Q

Dominant Negative mutation

A

a heterozygote produces a non-functional altered protein that also prevents the normal gene product from functioning; exerts a dominant effect (ie nonfunctional factor may bind DNA, thus preventing functional factor from binding)

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100
Q

Linkage disequilibrium

A

tendency for certain alleles at 2 linked loci to occur together more often than expected by chance; measured in a popl

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101
Q

Lyonization

A

random X-inactivation in females

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102
Q

Mosaicism

A

cells in body differ in genetic makeup d/t postfertilization loss of genetic info during mitosis
*germ-line/gonadal mosaic - child has a disease not carried by parent’s somatic cells

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103
Q

Locus heterogeneity

A

mutations at different loci can produce same phenotype

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104
Q

heteroplasmy

A

presence of both normal and mutated mitochondrial DNA –> so, have variable expression in mitochondrial inherited disease

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105
Q

uniparental disomy

A

kid gets 2 copies of a chromosome from 1 parent, none from the other

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106
Q

Hardy-Weinberg equations and what does the law assume?

A 
p^2 + 2pq + q^2 = 1
p + q = 1
p^2 = freq of homozygosity for p
q^2 = freq of homozygosity for q
2pq = freq of heterozygosity (carrier freq)

if X-linked:

  • males = q
  • females = q^2

Law assumes:

  • no mutation
  • no selection
  • random matig
  • no migration
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107
Q

Prader-Willi vs Angelman’s syndrome

A

both due to inactivation or deletion of genes on chromosome 15
-due to imprinting (1 allele is inactive d/t methylation); may also be d/t uniparental disomy
P-W: maternal allele is inactivated; paternal allele should be active but’s deleted; mental retardation, hyperphagia, obesity, hypogonadism, hypotonia

Angelman’s: inactive paternal allele; maternal allele should be active but is deleted; “happy puppet” –> MR, seizures, ataxia, inappropriate laughter.

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108
Q

Mitochondrial myopathies

A

seen in all offspring of infected mother

  • leber’s hereditary optic neuropathy (acute loss of central vision)
  • myoclonic epilepsy
  • mitochondrial encephalopathy
  • “ragged red fibers” on micrsocopy
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109
Q

Locus heterogeneity

A

mutations at different loci can produce same phenotype

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110
Q

heteroplasmy

A

presence of both normal and mutated mitochondrial DNA –> so, have variable expression in mitochondrial inherited disease

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111
Q

uniparental disomy

A

kid gets 2 copies of a chromosome from 1 parent, none from the other

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112
Q

Hardy-Weinberg equations and what does the law assume?

A 
p^2 + 2pq + q^2 = 1
p + q = 1
p^2 = freq of homozygosity for p
q^2 = freq of homozygosity for q
2pq = freq of heterozygosity (carrier freq)

if X-linked:

  • males = q
  • females = q^2

Law assumes:

  • no mutation
  • no selection
  • random matig
  • no migration
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113
Q

Prader-Willi vs Angelman’s syndrome

A

both due to inactivation or deletion of genes on chromosome 15
-due to imprinting (1 allele is inactive d/t methylation); may also be d/t uniparental disomy
P-W: maternal allele is inactivated; paternal allele should be active but’s deleted; mental retardation, hyperphagia, obesity, hypogonadism, hypotonia

Angelman’s: inactive paternal allele; maternal allele should be active but is deleted; “happy puppet” –> MR, seizures, ataxia, inappropriate laughter.

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114
Q

Mitochondrial myopathies

A

seen in all offspring of infected mother

  • leber’s hereditary optic neuropathy (acute loss of central vision)
  • myoclonic epilepsy
  • mitochondrial encephalopathy
  • “ragged red fibers” on micrsocopy
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115
Q

cell signaling defect of fibroblast growth factor (FGF) Receptor 3

A

Achondroplasia

  • dwarfism, short limbs (but normal head and trunk)
  • assoc with advanced paternal age
  • autosomal dominant
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116
Q

90% of cases are due to mutation in PKD1 (on chrom 16)

A

ADPKD (autosomal dominant polycystic kidney disease)

  • autosomal dominant
  • ALWAYS BILATERAL, massive enlargement of kidneys d/t multiple cysts
  • flank pain, hematuria, hypertension, progressive renal failure
  • assoc with polycystic liver disease, berry aneurysms, mitral valve prolapse
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117
Q

Mutations of APC gene on chromosome 5

A

Familial Adenomatous Polyposis

  • autosomal dominant
  • colon covered with adenomatous polyps after puberty
  • progresses to colon cancer, so have to do colonectomy
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118
Q

Elevated LDL d/t defective/absent LDL receptor, tendon xanthomas, atherosclerosis and MI early in life

A

Familial hypercholesterolemia (hyperlipidemia type IIA)

  • autosomal dominant
  • heterozygotes: cholesterol approx 300 mg/dL
  • homozygotes: cholesterol approx 700 + mg/dL; may develop MI before age 20
119
Q

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

A
  • autosomal dominant, inherited disorder of blood vessels

- telangiectasia, recurrent epistaxis, skin discolorations, arteriovenous malformations

120
Q

spectrin or ankyrin defect

A

Hereditary spherocytosis

  • autosomal dominant
  • spheroid RBCs, d/t spectrin or ankyrin defect (responsible for RBC structure)
  • hemolytic anemia
  • increased MCHC (mean cell hemoglobin concentration)
  • dx by osmotic fragility test
  • splenectomy = curative
121
Q

CAG trinucleotide repeats; gene on chromosome 4

A

Huntington’s disease

  • autosomal dominant
  • depression, dementia, choreiform mvmnts, caudate atrophy, decreased GABA and decreased ACh
  • symptoms between 20-50 yo
122
Q

Fibrillin gene mutation

A

Marfan’s syndrome

  • autosomal dominant
  • connective tissue disorder affecting skeleton, heart, eyes
  • tall, long extremities, pectus excavatum, hyperextensive joints, arachnodactyly
  • cystic medial necrosis of aorta –> aortic incompetence, dissecting aorta, berry aneurysms; floppy mitral valve
  • subluxation of lenses
123
Q

inheritance pattern of the MEN syndromes (multiple endocrine neoplasias)

A

autosomal dominant

-MEN 2A and 2B are associated with ret gene

124
Q

cafe au lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas), skeletal disorders (ie scoliosis), optic pathway gliomas

A

Neurofibromatosis type 1 = von Recklinghausen’s disease

  • autosomal dominant
  • on chrom 17
125
Q

Bilateral acoustic schwannomas, juvenile cataracts

  • what disorder is this?
  • what’s its mode of inheritance?
  • what gene is mutated and on what chromosome?
A

Neurofibromatosis type 2

  • autosomal dominant
  • NF2 gene on chromosome 22
126
Q

Tuberous Sclerosis

  • mode of inheritance?
  • Findings?
A
  • autosomal dominant
  • incomplete penetrance and variable presentation
  • Findings: facial lesions (adenoma sebaceum), hypopigmented ash-leaf spots, coritcal and retinal hamartomas, seizures, MR, renal cysts, renal angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas
127
Q

ash leaf spots (hypopigmented lesions on skin) + cardiac rhabdomyomas (+other possible symptoms too…)

A

Tuberous sclerosis

128
Q

Deletion of VHL gene on chromosome 3

A

von Hippel-Lindau disease

  • autosomal dominant
  • deletion of VHL gene = tumor suppressor gene; get constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors
  • hemangioblastomas of retina/cerebellum, medulla
  • 50% of pts develop multiple bilateral renal cell carcinomas and other cancers
129
Q

List the X-linked recessive disorders

A 
"Be Wise, Fool's GOLD Heeds Silly Hope"
-Bruton's agammaglobulinemia
-Wiskott-Aldrich syndrome
-Fabry's disease
-G6PD deficiency
-Ocular albinism (general albinism = aut recessive!)
-Lesch-Nyhan syndrome
-Duchenne's (and Becker's) muscular dystrophy
-Hunter's Syndrome
-Hemophilia A and B
...also, Fragile X....
130
Q

meconium ileus in a newborn. think:

A
  • Cystic fibrosis

- Hirschsprung’s disease

131
Q

CFTR gene mutation; mode of inheritance? Function of gene normally?

A

Cystic Fibrosis

  • autosomal recessive
  • CFTR gene codes for transmembrane protein that puts Cl from cell into lumen of pancreatic ducts and into lumen of airways; Na follows Cl into lumen, and water follows Na. But, with CFTR defect (abnormal protein folding), decreased water into lumen –> thick mucus

-mucus plugs lungs, pancreas, liver..

132
Q

most common lethal genetic disease of Caucasians?

A

cystic fibrosis

133
Q

recurrent pulmonary infections + malabsorption + caucasian child? Think:

A

cystic fibrosis

134
Q

Why are males with CF infertile?

A

bilateral absence of vas deferens

135
Q

Treatment for CF pts?

A
  • N-acetylcysteine (inhaled; loosens mucus plugs)
  • antibiotics (even fluoroquinolone in kids)
  • fat soluble vitamins: A, D, E, K
  • pancreatic enzymes
136
Q

Longest known human gene?

A

Dystrophin gene (DMD) –> mutated in Duchenne’s and Becker’s muscular dystrophy

137
Q

Defect affecting the methylation and expression of the FMR1 gene and trinucleotide repeat of CGG?

A

Fragile-X syndrome

  • X-linked defect
  • 2nd most common cause of genetic MR
  • MR, enlarged testes, long face, large jaw, large everted ears, autism, mitral valve prolapse
138
Q

What are the 4 trinucleotide repeat expansion diseases (and what’s being repeated)?

A

“Tri Hunting for my Fried Eggs (X)”

1) Huntington’s disease (CAG)
2) Myotonic dystrophy (CTG)
3) Friedrich’s ataxia (GAA)
4) Fragile X (CGG)
- -> all may show anticipation!

139
Q

flat facies, epicanthal folds, excessive skin at nape of neck, gap between 1st 2 toes, duodenal atresia, congenital heart disease

A

Down’s syndrome

140
Q

What does may a 1st trimester ultasound of a fetus with trisomy 21 show?

A

increased nuchal translucency

141
Q

decreased alpha-fetoprotein
increased beta-hCG
decreased estriol
increased inhibin A

A

Down’s syndrome

142
Q

decreased alpha-fetoprotein
decreased beta-hCG
decreased estriol
normal inhibin A

A

Edward’s syndrome (trisomy 18)

143
Q

MR, rocker-bottom feet, small jaw, low-set ears, clenched hands, congenital heart disease

A

Edward’s syndrome (trisomy 18)

144
Q

Pregnancy quad screen results in Patau’s syndrome (trisomy 13)

A

Normal alpha-fetoprotein, beta-hCG, estriol, inhibin A

145
Q

MR, rocker-bottom feet, small eyes, cleft lip/palate, holoprosencephaly (single mid-line eye), polydactyly, congenital heart disease

A

Patau’s syndrome (trisomy 13)

146
Q

Which chromosomes are commonly involved in Robertsonian translocations?

A

13, 14, 15, 21, 22

147
Q

MR, microcephaly, high-pitched crying, epicanthal folds, VSD (or other cardiac abnormalities)

A

Cri-du-chat syndrome (congenital microdeletion of short arm of chromosome 5)

148
Q

distinctive “elfin” facies, MR, hypercalcemia (and sensitivity to vitamin D), well-developed verbal skills and very friendly with strangers, CV problems

A

William’s syndrome (think of Will ferrel in “Elf”)

-d/t congenital microdeletion of long arm of chromosome 7 (including elastin gene)

149
Q

90% of pts with DiGeorge syndrome have a deletion where?

A

22q11 deletion

150
Q

Symptoms of microdeletion at chromosome 22q11:

A

variable, but includes CATCH-22:

  • Cleft palate
  • Abnormal facies
  • Thymic aplasia (prob with development of 3rd and 4th branchial pouches) –> T-cell deficiency
  • Cardiac defects
  • Hypocalcemia (d/t parathyroid aplasia)
  • see in 90% of DiGeorge pts
  • see in Velocardiofacial syndrome (palate, facial, and cardiac defects)
151
Q

List the fat-soluble vitamins

A

A, D, E, K

  • absorption depends on ileum and pancreas
  • may have to supplement in CF, sprue, or mineral oil intake (b/c all cause malabsorption/steatorrhea)
152
Q

Water-soluble vitamins

A 
B1
B2
B3
B5
B6
B12
C
Biotin
Folate
153
Q

B-complex deficiencies often result in:

A

dermatitis, glossitis, diarrhea

154
Q

Which vitamin is:

  • retinol
  • thiamine
  • riboflavin
  • niacin
  • pantothenate
  • pyridoxine
  • cobalamin
  • ascorbic acid
A 
retinol = vitamin A
thiamine = vitamin B1
riboflavin = vitamin B2
niacin = vitamin B3
pantothenate = vitamin B5
pyridoxine = vitamin B6
cobalamin = vitamin B12
ascorbic acid = vitamin C
155
Q

baby born with cleft palate, cardiac abnormalities. which vitamin may have been in excess in mother?

A

Vitamin A = retinol

–> in excess has terotegenic effects; so, don’t give isoretinoin (acne med) to pregnant women

156
Q

which vitamin may be used to treat measles and AML-M3?

A

Vitamin A (Retinol)

157
Q

Deficiency in Vitamin A causes night blindness and dry skin. Why?

A

Vitamin A = constituent of visual pigments in retina; essential for normal differentiation of epithelial cells into specialized tissue.

158
Q

TPP =Thiamine pyrophosphate (Thiamine = B1) = cofactor in what 4 reactions?

A

1) Pyruvate dehydrogenase (glycolysis)
2) alpha-ketoglutarate dehydrogenase (TCA cycle)
3) Transketolase (HMP shunt)
4) Branched-chain AA dehydrogenase

159
Q

Deficiency in vitamin B1 (Thiamine)?

A
  • impaired glucose breakdown (b/c need TPP as cofactor in glycolysis and TCA cycles, so get ATP depletion); Beriberi (dry/wet), Wernicke-Korsakoff
  • malnutrition, alchoholics
160
Q

Wernicke-Korsakoff syndrome

A

d/t thiamine deficiency
Wernicke: Triad: confusion, ophthalmoplegia, ataxia
Korsakoff: confabulation, personality change, memory loss (permanent)

161
Q

peripheral neuropathy, symmetrical muscle wasting, especially distal muscles; due to a vitamin deficiency

A

dry beriberi

162
Q

dilated cardiomyopathy (high-output cardiac failure), edema, symmetrical peripheral neuropathy; due to a vitamin deficiency

A

wet beriberi

163
Q

Cheilosis (inflammation of lips, scaling and fissures at corners of the mouth), Corneal vascularization; what vitamin is deficient?

A

Vitamin B2 (riboflavin); cofactorin oxidation and reduction (FADH2)

164
Q

Diarrhea, Dermatitis, Dementia; also: glossitis

A

Pellagra = vitamin B3 (niacin) deficiency

165
Q

symptom of vitamin B3 excess?

A

Facial flushing (niacin = treatment of choice to increase HDL levels; side effect = facial flushing!)

166
Q

Why may one get a B3 deficiency from:

  • Hartnup disease?
  • Malignant carcinoid syndrome?
  • Isoniazid?
A

Vit B3 is derived from Tryptophan and requires vitamin B6 for synthesis, so:

  • Hartnup disease: have decreased tryptophan absorption, so decreased B3
  • malignant carcinoid syndrome: have increased tryptophan metabolism
  • Isoniazid: decreased B6 (so, give B6 = pyridoxine to pts on INH!)
167
Q

Which vitamin is an essential component of CoA and fatty acid synthase?

A

Vitamin B5 = pantothenate (“pento-thenate”)

168
Q

What 2 med types may induce vitamin B6 deficiency?

A

Isoniazid and oral contraceptives

169
Q

Main causes of cobalamin (vit B12) deficiency?

A

1) Malabsorption: sprue, enteritis, Diphyllobothrium latum
2) no intrinsic factor (pernicious anemia, gastric bypass surgery)
3) no terminal ileum (Crohn’s)

*deficiency can cause macrocytic, megaloblastic anemia; neurologic symptoms

170
Q

Schilling test

A

detect etiology of Vitamin B12 (cobalamin) deficiency

171
Q

Most common vitamin deficiency in US?

A

folic acid

172
Q

deficiency in folic acid (not in pregnancy/just normal):

A

macrocytic, megaloblastic anemia (no, neuro symptoms, unlike B12 deficiency)

173
Q

SAM (S-adenosyl-methionine):

  • what does it do?
  • how is it formed? (what cofactors are needed in its formation)
  • what important reaction is it required for?
A

transfers methyl units!
ATP + Methionine => SAM
*need vitamin B12 and folate to regenerate methionine, and thus SAM
*SAM is required for conversion of NE–>Epinephrine

174
Q

excessive ingestion of raw eggs, may cause what deficiency?

A

Biotin deficiency! Dute to avidin in eggs, binds biotin

175
Q

Biotin is a cofactor in what 3 reactions:

A

1) pyruvate carboxylase: (pyruvate–>oxaloacetate)
2) acetyl-CoA carboxylase: acetyl CoA–>malonyl-CoA
3) propionyl-CoA carboxylase: propionyl-CoA–>methylmalonyl-CoA

176
Q

swollen gums, bruising, hemarthrosis, anemia, poor wound healing

A

scuvry (vit C def; symptoms for collagen synthesis defect)

177
Q

3 functions of vitamin C:

A

1) hydroxylation of proline and lysine in collagen synthesis
2) helps iron absorption (keeps Fe in a reduced state)
3) conversion of dopamine to NE (dopamine beta-hydroxylase)

178
Q 
What forms of vitamin D are these?
D2 =Ergocalciferol 
D3 = Cholecalciferol 
25-OH D3
1,25-(OH)2D3 = calcitriol
A

D2 - ingested in plants
D3 - consumed in milk, formed in sun-exposed skin
25-OH-D3 - storage form
1,25-OH2D3 = calcitriol = active form

179
Q

function of vitamin E? Deficiency causes?

A 
function = antioxidant; protects RBCs and membranes from free radical damage
deficiency: hemolytic anemia; weakness, posterior column and spinocerebellar tract demyelination
180
Q

Neonatal hemorrhage with increased PT and increased aPTT, but normal BT? (vit deficiency)

A

vitamin K deficiency (b/c vit K is synthesized by intestinal flora, but neonatal intestines are sterile, so can’t synthesize; give neonates vit K injection after birth)

181
Q

Delayed wound healing, hypogonadism, decreased adult hair (axillary, facial, pubic), ansomia - vit deficiency?

A

Zinc deficiency

182
Q

Vitamin K is necessary for the synthesis of what heme factors/proteins?

A

Clotting factors: 10, 9, 7, 2
Proteins C and S
*Warfarin = vit K antagonist

183
Q

Fomepizole

A

inhibits alcohol dehydrogenase (ehtanol–>acetaldehyde); antidote for methanol or ethylene glycol poisoning

184
Q

Disulfiram - “antibuse”

A

inhibits acetaldehyde dehydrogenase (acetaldehyde–>acetate); get acetaldehyde accumulation–>hang-over symptoms!

185
Q

How may ethanol lead to hypoglycemia and acidosis?

A

ethanol metabolism increases the NADH/NAD ratio in the liver, causing: pyruvate–>lactate and Oxaloacetate–>malate

  • this inhibits gluconeogenesis and stimulates fatty acid synthesis –> hypoglycemia and hepatic fatty change
  • also: overproduction of lactate–> acidosis
186
Q

Kwashiorkor vs Marasmus

A

Kwashiorkor- protein deficiency; edema (big belly), skin lesions, fatty liver (b/c decreased apolipoprotein synthesis)
Marasmus- malnutrition; muscle wasting, skinny, may have some edema

187
Q

Actions of:

  • kinases
  • phosphorylase
  • phosphatase
  • dehydrogenase
  • carboxylase
A

kinases- add a P, uses ATP
phosphorylases - add a P, does not use ATP
phosphotase - removes a P
dehydrogenase - oxidizes
carboxylase - transfers CO2 groups with help of biotin

188
Q

rate limiting enzyme of glycolysis?

A

PFK-1

189
Q

rate-limiter of gluconeogenesis?

A

F-1,6-BP

190
Q

rate limiter of TCA cycle?

A

isocitrate dehydrogenase

191
Q

rate-limiter of glycogen synthesis

A

glycogen synthase

192
Q

rate-limiter of glycogenolysis

A

glycogen phosphorylase

193
Q

rate-limiter of HMP shunt

A

G6PD

194
Q

rate-limiter of de novo pyrimidine synthesis

A

CMP 2

195
Q

rate-limiter of de novo purine synthesis

A

glutamine-PRPP amidotransferase

196
Q

rate limiter of urea cycle

A

CMP 1

197
Q

rate limiter of FA synthesis

A

ACC (acetyl-CoA carboxylase)

198
Q

rate limiter of FA oxidation

A

Carnitine acyltransferase I

199
Q

rate limiter of ketogenesis

A

HMG-CoA synthase

200
Q

rate limiter of cholesterol synthesis

A

HMG-CoA reductase

201
Q

rate-limiter of heme synthesis

A

aminolevulinate synthase

202
Q

rate-limiter of bile acid synthesis

A

7-alpha-hydroxylase

203
Q

Metabolic processes: Glycolysis, Gluconeogenesis, TCA cycle, acetyl-CoA production, HMP shunt, oxidative phosphorylation, Urea cycle, FA oxidation, FA synthesis, protein synthesis, steroid synthesis, heme synthesis:

  • which take place in cytoplasm?
  • which in mictochondria?
  • which in both cytoplasm and mitochondria?
A

Cytoplasm: Glycolysis, FA synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER)
Mitochondria: FA oxidation, acetyl-CoA production, TCA cycle, oxidative phosphorylation
Both: Heme synthesis, Urea cycle, Gluconeogenesis (HUG :))

204
Q

Which 3 reactions in metabolism require TPP (thiamine cofactor)?

A

1) Transketolase (HMP shunt: ribulose-5-P –> fructose-6-P)
2) Pyruvate dehydrogenase (glycolysis/acetyl CoA prod: pyruvate–> acetyl CoA)
3) alpha-ketoglutarate dehydrogenase: alpha-ketoglutarate–>succinyl CoA

205
Q

Which 3 metabolic reactions require a biotin cofactor?

A

1) ACC: acetyl-CoA–>malonyl CoA
2) pyruvate carboxylase: pyruvate–>oxaloacetate
3) propionyl CoA carboxylase: propionyl-CoA–>methylmalonyl CoA

206
Q

which metabolic reaction requires vitamin B12 (cobalamin)?

A

methylmalonyl-CoA –> succinyl CoA

207
Q

How many ATP are produced per glucose molecule (aerobic in heart/liver; aerobic in muscle; anaerobic)?

A

Aerobic metabolism via malate aspartate shuttle in heart and liver: 32 ATP/glucose
Aerobic via glycerol-3-phosphate shuttle in muscle: 30 ATP/glucose
Anaerobic: 2 ATP/glucose

208
Q

What do these carriers carry:

  • ATP
  • NADH/NAD/FADH2
  • Coenzyme A
  • Lipoamide
  • Biotin
  • Tetrahydrofolates
  • SAM
  • TPP
A
  • ATP –> phophoryl groups
  • NADH/NAD/FADH2 –> electrons
  • coenzyme A –> acyl groups
  • lipoamide –> acyl groups
  • biotin –> CO2
  • tertrahydrofolates –> 1 Carbon units
  • SAM –> CH3 groups
  • TPP –> Aldehydes
209
Q

NADPH:

  • what process is it a product of?
  • list 4 processes it is used in:
A
  • NADPH = product of HMP shunt (why G6PD is so important!)
  • NADPH is used in:
    1) anabolic processes (ie steroid and FA synthesis)
    2) respiratory burst (ie in phagolysosomes)
    3) P-450
    4) glutathione reductase (protects RBCs from oxidative damage by oxygen free radicals)
210
Q

Hexonkinase vs Glucokinase:

  • where is it located?
  • affinity/km?
  • capacity/vmax?
  • induced by insulin?
  • feedback inhibition on hexokinase/glucokinase?
A
  • both can catalyze glucose –> G-6-P
  • Hexokinase:
  • ubiquitous
  • high affinity/low km
  • low capacity/low vmax
  • uninduced by insulin
  • Glucokinase:
  • liver and Beta-cells of pancreas
  • low affinity/high km
  • high capacity/high vmax
  • induced by insulin
*Feedback inhibition:
G-6-P---> inhibits hexokinase 
F-6-P ---> inhibits glucokinase 
ATP --> inhibits both (AMP stimulates both)
Citrate --> inhibits both
211
Q

Pyruvate dehydrogenase complex: what are the 5 cofactors needed for the 3 enzymes in the complex?

A

“Tender Loving Care For No one”

1) Thiamine/TPP/B1/Pyrophosphate
2) Liopoic acid
3) CoA (B5;Pantothenate)
4) FAD (B2, riboflavin)
5) NAD (B3, niacin)

***note: same cofactors are used in the alpha-ketoglutarate dehydrogenase complex, in the TCA cycle (alpha-ketoglutarate –> succinyl CoA)

212
Q

Pyruvate dehydrogenase deficiency: what’s the treatment?

A

get lactic acidosis, d/t backup of substrate (pyruvate and alanine)
-treat by intake of ketogenic nutrients: high fat content or lysine and leucine (the only purely ketogenic AA’s)

213
Q

What are the 4 fates of pyruvate?

A

1) Acetyl CoA (enters TCA cycle)
2) Oxaloacetate (replenish TCA cycle, or converted to PEP and used in gluconeogenesis)
3) Lactate (end of anaerobic glycolys: pthwy for RBCs, leukocytes, kidney medulla, lens, testes, cornea)
4) Alanine (carries amino groups to liver from muscle)

214
Q

5 cofactors required for the alpha-ketoglutarate dehydrogenase complex (in the TCA cycle)?

A

same as for the Pyruvated Dehydrogenase complex!:

  • B1
  • B2
  • B3
  • B5
  • Lipoic acid

(or, “Tender Loving Care For No one”: Thiamine=B1, Lipoic Acid, CoA =B5, FAD =B2, NAD=B3)

215
Q

Electron transport chain: NADH and FADH2 yield how many ATP?

A

1 NADH –> 3 ATP

1 FADH2 –> 2 ATP

216
Q

In what organ does gluconeogenesis mainly occur?

A

mostly in liver (also in kidney, intestinal epithelium)

217
Q

Heinz bodies

A

oxidized hemoglobin precipitated within RBCs; seen in G6PD deficiency

218
Q

Bite cells

A

result from phagocytic removal of Heinz bodies by splenic macrophages; seen in G6PD deficiency

219
Q

defect in fructokinase

A
  • essential fructosuria
  • autosomal recessive
  • mild/asymptomatic disease, because fructose doesn’t enter cells
  • fructose in blood and urine
220
Q

Aldolase B deficiency

A
  • Fructose intolerance
  • autosomal recessive
  • get accumulation of Fructose-1-Phosphate, so decreased Phosphate availability –> inhibits glycogenolysis and gluconeogenesis
  • symptoms: hypoglycemia, jaundice, cirrhosis, vomiting
  • treat by decreasing intake of fructose and sucrose
221
Q

Galactokinase deficiency

A
  • mild autosomal recessive disease; get galactose in blood and urine
  • infants may have infantile cataracts, and may fail to track objects or develop a social smile
222
Q

absence of Galactose-1-phosphate uridyltransferase

A
  • classic galactosemia
  • autosomal recessive
  • galactitol accumulates, and may deposit in lens of eyes
  • symptoms: FTT, jaundice, hepatomegaly, infantile cataracts; MR; also: pts can’t tolerate milk early in life! (b/c lactose = galactose + glucose)
  • treat by excluding galactose and lactose from diet
223
Q

infantile cataracts? think:

A

galactokinase deficiency or classic galactosemia

224
Q

Aldolase reductase

A

converts glucose to sorbitol.

  • some tissues can go on to convert the sorbitol to fructose, via sorbitol dehydrogenase (in liver, ovaries, seminal vesicles)
  • other tissues (schwann cells, lens, retina, kidneys) only have aldose reductase, so sorbitol gets trapped in cells –> osmotic damage (ie cataracts, retinopathy, peripheral neuropathy seen in diabetic patients with chronic hyperglycemia)
225
Q

List the essential AAs:

A

“PVT TIM HALL” = Phe, Val, Thr, Trp, Ile, Met, His, Arg, Leu, Lys

  • glucogenic: met, val, arg, his
  • glucogenic/ketogenic: ile, phe, thr, trp
  • ketogenic: leu, lys
226
Q

which 2 amino acids are required during periods of growth (so many be found in body building supplements)?

A

Arg and His

227
Q

Lactulose

A

sweet syrup that can’t be digested; used as treatment for hyperammonemia: acidifies the GI and traps NH4+ for excretion

228
Q

orotic acid in blood/urine, decreased BUN, symptoms of hyperammonemia

A

Ornithine transcarbamoylase deficiency:

  • most common urea cycle disorder; X-linked recessive
  • can’t eliminate ammonia, can’t make urea
  • excess carbamoyl phosphate is converted to orotic acid (part of the pyrimidine synthesis pathway!)
229
Q

Why may a B6 deficiency lead to seizures?

A

B6 is a cofactor in the formation of GABA from Glutamate (via glutamate decarboxylase)
-if B6 deficiency, then decrease GABA (inhibitory), so decreased inhibition –> increased neuroexcitability –> seizures.

230
Q

Deficiency in phenylalanine hydroxylase?

A

PKU (enzyme that converts phenylalanine–>tyrosine hydroxylase in catecholamine synthesis; without it, get accumulation of phenylalanine and thus excess phenylketones in urine; tyrosine becomes essential)

231
Q

“malignant phenylketonuria” cause?

A

deficiency/absence of THB (tetrahydrobiopterin cofactor), which is required for phenylalanine hydroxylase to convert Phenylalanine to tryosine, and tyrosine to Dopa

232
Q

MR, growth retardation, seizures, fair skin, eczema, musty body odor

A

PKU (fair skin, because can’t make dopa, and thus can’t make melanin, b/c: dopa–>melanin)
-autosomal recessive

233
Q

treatment for PKU

A

restrict phenylalanine in diet (aspartame); increase intake of tyrosine; also: give THB, if it’s deficient.

234
Q

dark connective tissue, brown pigmented sclera, urine turns black after prolonged exposure to air

A

Alkaptonuria; deficiency in homogentisic acid oxidase (degrades tyrosine–>fumarate)
-autosomal recessive; benign disease

235
Q

Albinism causes? mode of inheritance?

A

Causes:

  • tyrosinase deficiency (can’t make melanin from tyrosine) = aut recessive
  • defective tyrosine transporters (so decreased tyrosine–>decreased melanin)
236
Q

tall stature, kyphosis, lens subluxation, atherosclerosis (stroke/MI), elevated levels of homocysteine in urine: Causes? Treatment?

A
  • Homocystinuria = autosomal recessive
  • Causes:
    1) cystathionine synthase deficiency (treat: decrease Met, increased Cysteine, increased B12 and folate)
    2) decreased affinity of cystathionine synthase for pyridoxal phosphate (active form of B6) (treat: increased B6 intake)
    3) homocysteine methyltransferase deficiency
237
Q

Lens subluxation:

A
  • Marfan’s

- Homocysteinuria

238
Q

hexagonal cysteine crystals on urinalysis:

A

= pathognomonic for cystinuria

239
Q

Cystinuria (“COLA defect”)

A

defect in renal proximal tubules –> decreased reabsorption (so increased secretion) of COLA:

  • Cysteine
  • Ornithine
  • Lysine
  • Arginine
  • autosomal recessive
  • may lead to cystine kidney stones
240
Q

Which amino acids should be avoided in maple syrup urine disease, and why?

A

Branched AA’s: Ile, Leu, Val –> b/c deficiency of alpha-keotacid dehydrogenase, so can’t degrade these AAs.

241
Q

Sodium Cyanide-Nitroprusside test

A

use to dx Cystinuria (causes urine to turn red-purple)

242
Q

What disease may lead to pellagra?

A

Hartnup disease:

  • aut recessive
  • tryptophan excretion in urine and decreased absorption from gut; niacin (vit B3) is derived from tryptophan, so get niacin deficiency –> pellagra = diarrhea, dementia, dermatitis, death
243
Q

In which organs/cells does glycogenolysis occur?

A

Skeletal muscle: glycogen–> glucose; glucose is rapidly metabolized during exercise

Hepatocytes: glycogen–> glucose to maintain blood sugar at appropriate levels

244
Q

Names of the 4 glycogen storage diseases:

A

“Very Poor Carbohydrate Metabolism”

1) Von Gierkes - type 1 (glucose-6-phosphatase def)
2) Pompes - type 2 (alpha-1,4-glucosidase = acid maltase def)
3) Coris - type 3 (debranching enzyme = alpha-1,6-glucosidase def)
4) McArdles - type 4 (skeletal muscle glycogen phosphorylase def)

245
Q

cardiomegaly and systemic findings leading to early death (by age 3) - which glycogen storage disease and what enzyme is deficient?

A

Pompe’s = type 2

-lysosomal alpha-1,4-glucosidase (acid maltase)

246
Q

severe fasting hypoglycemia, excessive glycogen in liver, increased blood lactate, hepatomegaly

A

Von Gierkes (type 1) = Glucose-6-Phosphatase deficiency (so can’t do gluconeogenesis or glycogenolysis)

247
Q

mild hypoglycemia, glycogen in liver, hepatomegaly, but normal blood lactate (because gluconeogenesis is intact)

A

Cori’s disease = type 3 = debranching enzyme/alpha-1,6-glucosidase deficiency

248
Q

painful muscle cramps, myoglobinuria with strenuous exercise - what glycogen storage disease?

A

mcardle’s - type 5; skeletal muscle glycogen phosphorylase deficiency

  • -> have increased glycogen in muscle, but can’t break it down.
  • -> does not affect longevity
249
Q

Which lysosomal storage diseases are X-linked recessive? What are the rest?

A

Fabry’s and Hunter’s are X-linked recessive

The rest are Autosomal recessive

250
Q

peripheral neuropathy of hands/feet, angiokeratomas, CV/renal disease, alpha-galactosidase A deficiency, ceramide trihexoside accumulation?

A

Fabry’s disease (XR)

251
Q

hepatosplenomegaly, aseptic necrosis of femur, bone crises, macrophages that look like crumpled tissue paper on microscopy, accumulation of glucocerebroside

A

Gaucher’s disease

252
Q

cherry red spot on macula, foam cells on microscopy, neurodegeneration, hepatosplenomegaly, accumulation of sphingomyelin

A

Niemann-Pick disease (“No man picks his nose with his sphinger!)

253
Q

cherry red spot on macula, lysosomes with onion skin, neurodegeneration, developmental delay, hexosaminidase A deficiency, GM2 ganglioside accumulation

A

Tay-Sachs (tay saX lacks heXoaminidase)

254
Q

optic atrophy, globoid cells, neuropathy, development delay, galctocerebroside accumulation

A

Krabbe’s disease

255
Q

ataxia and dementia, central and peripheral demyelination, cerebroside sulfate accumulation

A

Metachromatic leukodystrophy

256
Q

corneal clouding, airway obstruction, gargoylism, hepatosplenomegaly, development delay; heparan sulfate and dermatan sulfate accumulation

A

Hurler’s syndrome

257
Q

aggressive behavior + mild symptoms of Hurler’s syndrome (dev’l delay, gargoylism, airway obstruction, hepatosplenomegaly); heparan sulfate and dermatan sulfate accumulation

A

Hunter’s syndrome (XR)

258
Q

Hypoketotic hypoglycemia (+ weakness and hypotonia)

A

Carnitine deficiency: can’t transport LCFAs into mitochondria, so get toxic accumulation in cytoplasm

259
Q

how many kcal from 1 g protein, carb, fat?

A

1 g protein –> 4 kcal
1 g carb –> 4 kcal
1 g fat –> 9 kcal

260
Q

LCAT = lecithin-cholesterol acyltransferase: what does it do?

A

takes cholesterol and puts it into HDL particles (catalyzes esterification of cholesterol)

261
Q

CETP = cholesterol ester transfer protein: what does it do?

A

allows HDL to deposit cholesterol into LDL, etc.. (mediates transfer of cholesterol esters to other lipoprotein particles)

262
Q

Apolipoprotein E

A

mediates VLDL and chylomicron remanant uptake by liver cells

263
Q

Apolipoprotein A1

A

activates LCAT (for cholesterol esterification)

264
Q

Apolipoprotein C-11

A

lipoprotein lipase cofactor (LPL –> degrades TG circulating in chylomicrons and VLDLs)

265
Q

apolipoprotein B-48

A

mediates chylomicron secretion by the intestine and chylomicron assembly

266
Q

Apolipoprotein B-100

A

binds LDL receptor (LDL particle uptake by extrahepatic cells)

267
Q

familial dyslipidemia with increased chylomicrons, increased blood TG and cholesterol; pancreatitis, xanthomas…

A

type 1: hyper-chylomicronemia

-no increase risk for atherosclerosis

268
Q

familial dyslipidemia with increased LDL; atherosclerosis, Achilles xanthomas, corneal arcus; elevated blood cholesterol

A

type IIa - familial hypercholesterolemia

  • aut dominant
  • MI by age 20 if homozygous
269
Q

familial dyslipidemia with increased VLDL; increased blood TGS; pancreatitis

A

type IV - hypertriglyceridemia

-have hepatic overproduction of VLDL

270
Q

corneal clouding, airway obstruction, gargoylism, hepatosplenomegaly, development delay; heparan sulfate and dermatan sulfate accumulation

A

Hurler’s syndrome

271
Q

aggressive behavior + mild symptoms of Hurler’s syndrome (dev’l delay, gargoylism, airway obstruction, hepatosplenomegaly); heparan sulfate and dermatan sulfate accumulation

A

Hunter’s syndrome (XR)

272
Q

Hypoketotic hypoglycemia (+ weakness and hypotonia)

A

Carnitine deficiency: can’t transport LCFAs into mitochondria, so get toxic accumulation in cytoplasm

273
Q

how many kcal from 1 g protein, carb, fat?

A

1 g protein –> 4 kcal
1 g carb –> 4 kcal
1 g fat –> 9 kcal

274
Q

LCAT = lecithin-cholesterol acyltransferase: what does it do?

A

takes cholesterol and puts it into HDL particles (catalyzes esterification of cholesterol)

275
Q

CETP = cholesterol ester transfer protein: what does it do?

A

allows HDL to deposit cholesterol into LDL, etc.. (mediates transfer of cholesterol esters to other lipoprotein particles)

276
Q

Apolipoprotein E

A

mediates VLDL and chylomicron remanant uptake by liver cells

277
Q

Apolipoprotein A1

A

activates LCAT (for cholesterol esterification)

278
Q

Apolipoprotein C-11

A

lipoprotein lipase cofactor (LPL –> degrades TG circulating in chylomicrons and VLDLs)

279
Q

apolipoprotein B-48

A

mediates chylomicron secretion by the intestine and chylomicron assembly

280
Q

Apolipoprotein B-100

A

binds LDL receptor (LDL particle uptake by extrahepatic cells)

281
Q

familial dyslipidemia with increased chylomicrons, increased blood TG and cholesterol; pancreatitis, xanthomas…

A

type 1: hyper-chylomicronemia

-no increase risk for atherosclerosis

282
Q

familial dyslipidemia with increased LDL; atherosclerosis, Achilles xanthomas, corneal arcus; elevated blood cholesterol

A

type IIa - familial hypercholesterolemia

  • aut dominant
  • MI by age 20 if homozygous
283
Q

familial dyslipidemia with increased VLDL; increased blood TGS; pancreatitis

A

type IV - hypertriglyceridemia

-have hepatic overproduction of VLDL

284
Q

deficiencies in apo-B100 and apo-B48; FTT, steatorrhea, acanthocytosis, ataxia, night blindness

A

abetalipoproteinemia –> can’t synthesize lipoproteins b/c no apob100 and apob48

  • autosomal recessive
  • accumulation within enterocytes because can’t export absorbed lipid as chylomicrons
285
Q

facial lesions (adenoma sebaceum), hypopigmented ash-leaf spots, coritcal and retinal hamartomas, seizures, MR, renal cysts, renal angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas

A

Tuberous Sclerosis (variable presentations)

286
Q

3 mitochondrial disorders:

  • Leber hereditary optic neuropathy
  • myotonic epilepsy
  • MELA
A

1) Leber Hereditary optic neuropathy –> bilateral vision loss
2) Myoclonic epilepsy with ragged red fibers –> myoclonus, seizures, myopathy assoc with exercise; irregularly shaped muscle fibers on skeletal muscle biopsy
3) MELA = mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes–> seizures, stroke-like episodes with neuro-deficit, muscle weakness, increased serum lactate post-exercise and at rest

287
Q

Hypoglycemia after prolonged fasting, with inappropriately low levels of ketone bodies: What enzyme is deficient?

A

Impaired Beta-oxidateion/Degradation of Fatty Acids; Acyl-CoA dehydrogenase deficiency

288
Q

antibodies against collagen type 4?

A

=anti-glomerular basement membrane antibodies –> Goodpasture’s syndrome! (hemoptysis + oliguria)…

289
Q

recurrent nosebleeds, and pink spider-like lesions on oral and nasal mucosa, face, and arms.

A

Osler-Weber-Rendu syndrome = hereditary hemorrhagic telangiectasia

290
Q

How are sugars attached to nitrogen-containing bases in nucleotides?

A

N-glycosidic bonds

between sugars–>hydrogen bonds; between nucleotides–>phosphodiester bonds

291
Q

Which step in collagen synthesis is impaired in pts with scruvy?

A

Hydroxylation of specific proline and lysine residues on the pro-alpha collagen

292
Q

How does ethanol metabolism contriute to hypoglycemia?

A

increases NADH/NAD ratio in liver –> so, causes:

  • pyruvate–> lactate
  • and-
  • OAA–> malate
  • **So, inhibits gluconeogenesis and stimulates hepatic fatty change
  • **So, get overproduction of lactate–>acidosis; also overproduction of NADPH–>increased fatty acid synthesis
293
Q

What mechanism allows for the production of more than one protein by one human gene?

A

Alternative splicing

FirstAID (24 decks)

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