Biochemistry 1/2, First Aid for the USMLE Step 1 Flashcards
1
Q
DNA charge
A
Negative
2
Q
Histone charge
A
Positive
3
Q
Negatively charged DNA loops ___ around positively charged histone octamer to form nucleosome “___.”
A
Twice; beads on a string
4
Q
Histones are rich in the amino acids ___
A
Lysine and arginine
5
Q
___ binds to the nucleosome and to “linker DNA,” thereby stabilizing the chromatin fiber
A
H1
6
Q
DNA and histone synthesis occur during ___ phase of the cell cycle
A
S phase
7
Q
Condensed chromatin that appears darker on EM
A
Heterochromatin [Think HeteroChromatin, Highly Condensed]
8
Q
Less condensed chromatin that appears lighter on EM
A
Euchromatin
9
Q
Transcriptionally inactive chromatin, sterically inaccessible
A
Heterochromatin
10
Q
Transcriptionally active, sterically accessible
A
Euchromatin
11
Q
Inactive X chromosomes
A
Barr bodies
12
Q
Heterochromatin vs Euchromatin: Barr bodies
A
Heterochromatin
13
Q
Template strand ___ and ___ are methylated in DNA replication, which allows mismatch repair enzymes to distinguish between old and new strands in prokaryotes
A
Cytosine, adenine
14
Q
What methylation processes make DNA mute or repress DNA transcription
A
DNA methylation; histone methylation (repress or activate DNA transcription)
15
Q
Relaxes DNA coiling, allowing for transcription
A
Histone acetylation [Think Acetylation = Active]
16
Q
Purines
A
Adenine, Guanine [Think PURe As Gold]
17
Q
Pyrimidines
A
Cytosine, Uracil, Thymine [Think CUT the PY]
18
Q
Purines vs Pyrimidines: 2 rings
A
Purines [Pyrimidines = PYRamids can stand alone = 1 ring]
19
Q
Which pyrimidine has a methyl
A
Thymine [ Think THYmine has a meTHYl]
20
Q
What makes uracil
A
Deamination of cytosine
21
Q
Uracil is found in
A
RNA
22
Q
Thymine is found in
A
DNA
23
Q
Base pair with 2 hydrogen bonds
A
A-T [Think 2 AToms of hydrogen]
24
Q
Base pair with a higher melting point
A
G-C (3 H bonds)
25
Amino acids necessary for purine synthesis
Glycine, Aspartate, Glutamate [GAG]
26
Amino acid necessary for pyrimidine synthesis
Aspartate
27
A nucleoSide is composed of
Base + Sugar (ribose or deoxyribose)
28
A nucleoTide is made of
Base + Sugar + phosphaTe; linked by 3'-5' phosphodiester bond
29
De novo purine synthesis
1) Sugar + phosphate (PRPP) 2) Add base
30
De novo pyrimidine synthesis
1) Temporary base (orotic acid) 2) Add sugar + phosphate (PRPP) 3) Modify base
31
Which are synthesised first, ribonucleotides vs deoxyribonucleotides
Ribonucleotides are synthesized first and are converted to deoxyribonucleotides by ribonucleotide reductase
32
Carbamoyl phosphate is involved in what 2 metabolic pathways
1) De novo pyrimidine synthesis 2) Urea cycle
33
Inhibits dihydroorotate dehydrogenase (pyrimidine base production)
Leflunomide [dihydrOO leflOO]
34
Inhibit IMP dehydrogenase (purine base production)
Mycophenolate mofetil and ribavirin
35
Inhibits ribonucleotide reductase (pyrimidine base production)
Hydroxyurea
36
Inhibits de novo purine synthesis
6-MP and its prodrug azathioprine
37
Inhibits thymidilate synthase (dUMP>dTMP; pyrimidine base synthesis)
5-FU
38
Inhibits DHFR
1) MTX (humans) 2) TMP (bacteria) 3) Pyrimethamine (protozoa)
39
Inhibited by Allopurinol and Febuxostat in purine salvage pathway
Xanthine oxidase
40
Xanthine oxidase catalyses what 2 reactions in the purine salvage pathway
1) Hypoxanthine > xanthine 2) Xanthine > uric acid
41
Promotes excretion of uric acid in urine
Probenecid
42
Causes excess ATP and dATP > feedback inhibition of ribonucleotide reductase > prevents DNA synthesis > decreases lymphocyte count
Adenosine deaminase deficiency (one of the major causes of SCID)
43
Defective purine salvage due to absent HGPRT
Lesch-Nyhan syndrome
44
HGPRT catalyzes
1) Hypoxanthine to IMP 2) Guanine to GMP
45
Treatment of choice for Lesch-Nyhan
Allopurinol (2nd line: Febuxostat)
46
Genetic code feature: Each codon specifies only 1 amino acid
Unambiguous
47
Genetic code feature: Most amino acids are coded by multiple codons
Degenerate/ redundant
48
Genetic code feature: Read from a fixed starting point as a continuous sequence of bases
Commaless, nonoverlapping
49
Genetic code feature: Conserved throughout evolution
Universal
50
Amino acids encoded by only 1 codon each and are exceptions to degenerate/redundance feature of genetic code
1) Methionine 2) Tryptophan
51
Methionine, codon
AUG
52
Tryptophan, codon
UGG
53
Genetic code is universal except
In mitochondria
54
Y-shaped region along DNA template where leading and lagging strands are synthesized
Replication fork
55
Unwinds DNA template at replication fork
Helicase
56
Prevent strands from reannealing
Single-stranded binding proteins
57
Create a single- or double-stranded break in the helix to add or remove supercoils
DNA topoisomerases
58
Inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV
Fluoroquinolones
59
Prokaryotic DNA polymerase that elongates leading strand by adding deoxynucleotides to the 3_ end; has 5_>3_ synthesis and proofreads with 3_>5_ exonuclease
DNA polymerase III
60
Prokaryotic DNA polymerase that degrades RNA primer and replaces it with DNA
DNA polymerase I
61
Catalyzes the formation of a phosphodiester bond within a strand of double-stranded DNA (i.e., joins Okazaki fragments); SEALS
DNA ligase
62
An RNA-dependent DNA polymerase that adds DNA to 3_ ends of chromosomes to avoid loss of genetic material with every duplication
Telomerase
63
T/F Telomerase is found in both prokaryotes and eukaryotes
F, eukaryotes only
64
Severity of DNA damage from least to greatest
Silent, missense, nonsense, frameshift
65
Point mutations
1) Silent 2) Missense 3) Nonsense
66
Point mutation in which purine is replaced by purine or pyrimidine by another pyrimidine
Transition
67
Point mutation in which purine is replaced by a pyrimidine or pyrimidine by a purine
Transversion
68
Nucleotide substitution but codes for same (synonymous) amino acid
Silent
69
Nucleotide substitution resulting in changed amino acid
Missense
70
Nucleotide substitution resulting in early stop codon
Nonsense [Think STOP the NONSENSE]
71
Deletion or insertion of a number of nucleotides not divisible by 3, resulting in misreading of all nucleotides downstream, usually resulting in a truncated, nonfunctional protein
Frameshift
72
Type of mutation in Duchenne muscular dystrophy
Frameshift
73
Base change in silent mutation is usually at which position
3rd position
74
What do you call the base change in 3rd position of codon
tRNA wobble
75
A missense is called "conservative" if
The new amino acid is similar in chemical structure
76
Sickle cell disease is what type of mutation
Missense (glutamic acid>val)
77
Single strand DNA repair: Specific endonucleases release the oligonucleotides containing damaged bases; DNA polymerase and ligase fill and reseal the gap, respectively
Nucleotide excision repair
78
Nucleotide excision repair occurs in what phase of the cell cycle
G1
79
Single strand DNA repair: Important in repair of spontaneous/toxic deamination; occurs throughout the cell cycle
Base excision repair
80
What DNA repair mechanism is defective in xeroderma pigmentosum, which prevents repair of pyrimidine dimers because of ultraviolet light exposure
Nucleotide excision repair
81
What single strand DNA repair mechanism is defective in hereditary nonpolyposis colorectal cancer (HNPCC)
Mismatch repair
82
Mismatch repair occurs predominantly in which phase of the cell cycle
G2
83
Double strand DNA repair mechanism: Some DNA may be lost; mutated in ataxia telangiectasia and Fanconi anemia
Nonhomologous end joining
84
DNA and RNA are both synthesised in what direction
5'>3'
85
The ___ of the incoming nucleotide bears the triphosphate (energy source for bond)
5_ end
86
Protein synthesis is ___ to ___
N-terminus, C-terminus
87
mRNA is read from what end to what end
5' to 3'
88
Target of the 3_ hydroxyl attack
Triphosphate bond
89
Drugs blocking DNA replication often have modified ___, preventing addition of the next nucleotide ("chain termination")
3_ OH
90
mRNA start codon
AUG (rarely GUG) [Think inAUGurates protein synthesis]
91
AUG in eukaryotes codes for what amino acid
Methionine
92
AUG in prokaryotes codes for
N-formylmethionine (fMet)
93
Function of fMet
Stimulates neutrophil chemotaxis
94
mRNA stop codons
UGA, UAA, UAG [Think U Go Away, U Are Away, U Are Gone]
95
Site in the gene where RNA polymerase II and multiple other transcription factors bind to DNA upstream from gene locus
Promoter
96
AT-rich upstream sequence with TATA and CAAT boxes
Promoter
97
Stretch of DNA that alters gene expression by binding transcription factors
Enhancer
98
Site in the gene where negative regulators (repressors) bind
Silencer
99
RNA polymerase: Makes rRNA
RNA polymerase I
100
RNA polymerase: Makes mRNA
RNA polymerase II
101
RNA polymerase: Makes tRNA
RNA polymerase III
102
Most numerous RNA
rRNA [Rampant]
103
Largest RNA
mRNA [Massive]
104
Smalles RNA
tRNA [Tiny]
105
RNA polymerase: Opens DNA at promoter site
RNA polymerase II
106
RNA polymerase II is inhibited by what substance, which causes severe hepatotoxicty if ingested
alpha-amanitin, found in Amanita phalloides (death cap mushrooms)
107
Drug that inhibits RNA polymerase in prokaryotes
Rifampin
108
Drug that inhibits RNA polymerase in both prokaryotes and eukaryotes
Actinomycin D
109
How many RNA polymerases are then in prokaryotes?
Only 1 (makes all 3 kinds of RNA)
110
Initial RNA transcript in eukaryotes that is subsequently modified and becomes mRNA
Heterogenous nuclear RNA (hnRNA)
111
3 processes that occur in the nucleus following transcription
1) Capping of 5' end (7-methylguanosine cap) 2) Polyadenylation of 3' end 3) Splicing out of introns
112
Capped, tailed, and spliced RNA transcript is called
mRNA
113
Where does transcription occur
Nucleus
114
Where does translation occur
Cytosol
115
mRNA quality control occurs at
P-bodies in cytoplasm (also the site of mRNA storage)
116
Polyadenylation signal
AAUAA
117
Primary transcript combines with ___ and other proteins to form spliceosome
Small nuclear ribonucleoproteins (snRNPs)
118
Antibodies to snRNPs
Anti-Smith antibodies
119
Introns vs. exons: Contain the actual genetic information coding for protein
Exons
120
Introns vs. exons: Intervening noncoding segments of DNA
Introns
121
Introns vs. exons: Stay in the nucleus
Introns
122
RNA that assumes a cloverleaf form
tRNA
123
At which end of the tRNA is the anticodon found
Opposite the 3' aminoacyl end
124
Amino acid is covalently bound to which end of tRNA
3' end
125
This enzyme scrutinizes amino acid before and after it binds to tRNA, and if incorrect, bod is hydrolyzed
Aminoacyl-tRNA synthetase
126
T/F Accurate base pairing is usually required only in the first 2 nucleotide positions of an mRNA codon, so codons differing in the 3rd "wobble" position may code for the same tRNA/amino acid
T
127
Protein synthesis is initiated by
GTP hydrolysis
128
Ribosome site that receives incoming aminoacyl-tRNA
A site
129
Ribosome site that accommodates the growing peptide
P site
130
Ribosome site that holds empty tRNA as it exits
E site
131
At which ribosome subunit are the A, P, and E sites found
60S
132
___ catalyzes peptide bond formation and transfers growing polypeptide to amino acid in A site
rRNA ("ribozyme")
133
Posttranslational modification of protein: Removal of N- or C-terminal propeptides from zymogen to generate mature protein (e.g., trypsinogen to trypsin)
Trimming
134
Posttranslational modification of protein: Phosphorylation, glycosylation, hydroxylation, methylation, acetylation, and ubiquitination
Covalent alterations
135
Intracellular protein involved in facilitating and/or maintaining protein folding, e.g. heat shock proteins
Chaperone protein
136
Shortest phase of cell cycle
M phase
137
Constitutive regulator of the cell cycle
CDKs
138
Regulatory proteins that control cell cycle events; phase specific; activate CDKs
Cyclins
139
Phosphorylate other proteins to coordinate cell cycle progression; must be activated and inactivated at appropriate times for cell cycle to progress
Cyclin-CDK complexes
140
Inhibit G1-to-S progression, the mutation of which result in unrestrained cell division
Tumor suppressors, p53 and Rb
141
Phase of the cell cycle where DNA synthesis occurs
S phase
142
Phases of the cell cycle
G0 > G1 > S > G2 > M > G0 or G1
143
Cells that remain in G0, regenerate from stem cells
Permanent cells (neurons, skeletal and cardiac muscle, RBCs)
144
Cells that enter G1 from G0 when stimulated
Stable (quiescent) (hepatocytes, lymphocytes)
145
Cells that never go to G0, divide rapidly with a short G1. Most affected by chemotherapy.
Labile cells (bone marrow, gut epithelium, skin, hair follicles, germ cells)
146
Site of synthesis of secretory (exported) proteins and of N-linked oligosaccharide addition to many proteins
RER
147
Site of synthesis of cytosolic and organellar proteins
Free ribosomes
148
Site of steroid synthesis and detoxification of drugs and poisons
SER
149
SER is rich in
1) Hepatocytes 2) Steroid hormone- producing cells of the adrenal cortex 3) Gonads
150
Distribution center for proteins and lipids from the ER to the vesicles and plasma membrane
Golgi
151
Abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER; the absence or dysfunction of which causes protein accumulation in the cytosol
Signal recognition particle (SRP)
152
Vesicular trafficking protein: Golgi > Golgi (retrograde); cis-Golgi > ER
COPI
153
Vesicular trafficking protein: ER > cis-Golgi (anterograde)
COPII
154
Trans-Golgi > lysosomes; plasma membrane > endosomes (receptor- mediated endocytosis)
Clathrin
155
Membrane-enclosed organelle involved in catabolism of very-long-chain fatty acids, branched-chain fatty acids, and amino acids
Peroxisome
156
Barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins
Proteasome
157
Cell filament: Muscle contraction, cytokinesis
Microfilaments, e.g. actin
158
Cell filament: Maintain cell structure
Intermediate filaments, e.g. Vimentin, desmin, cytokeratin, lamins, glial fibrillary acid proteins (GFAP), neurofilaments
159
Cell filament: Movement, cell division
Microtubules, e.g. Cilia, flagella, mitotic spindle, axonal trafficking, centrioles
160
Immunohistochemical stain: Connective tissue
Vimentin
161
Immunohistochemical stain: Muscle
Desmin
162
Immunohistochemical stain: Epithelial cells
Cytokeratin
163
Immunohistochemical stain: Neuroglia
GFAP
164
Immunohistochemical stain: Neurons
Neurofilaments
165
Cylindrical structure composed of a helical array of polymerized heterodimers of _- and _-tubulin
Microtubule
166
Drugs that act on microtubules
[Microtubules Get Constructed Very Poorly] 1) Mebendazole (antihelminthic) 2) Griseofulvin (anti fungal) 3) Colchicine (anti gout) 4) Vincristine/Vinblastine (anticancer) 5) Paclitaxel (anticancer)
167
9 + 2 arrangement of microtubule doublets
Cilia
168
Immotile cilia due to a dynein arm defect; immotility in both men and women (immotile sperm and dysfunctional fallopian tube cilia)
Kartagener syndrome/primary ciliary dyskinesia
169
Inhibits Na-K ATPase pump by binding to K+ site
Ouabain
170
Drugs that directly inhibit the Na+-K+ ATPase, which leads to indirect inhibition of Na+/Ca2+ exchange > increase in [Ca2+]i > increase in cardiac contractility
Cardiac glycosides (digoxin and digitoxin)
171
Most abundant protein in the human body
Collagen
172
MC type of collagen (90%)
Type I
173
Synthesizes type I collagen in bone
Osteoblasts
174
Sites of type I collagen
Bone (made by osteoblasts), Skin, Tendon, dentin, fascia, cornea, late wound repair
175
Sites of type II collagen
Cartilage (including hyaline), vitreous body, nucleus pulposus
176
Sites of type III collagen
Reticulin—skin, blood vessels, uterus, fetal tissue, granulation tissue
177
Sites of type IV collagen
Basement membrane, basal lamina, lens
178
Collagen type: Decreased production in osteogenesis imperfecta type I
I
179
Collagen type: Deficient in the uncommon, vascular
| type of Ehlers-Danlos syndrome
III
180
Collagen type: Defective in Alport syndrome
IV
181
Collagen type: Targeted by autoantibodies in Goodpasture syndrome
IV
182
In what cells is collagen synthesized
Fibroblasts
183
In what organelle is collagen synthesized
RER
184
Steps in collagen synthesis that take place in fibroblasts
1) Synthesis (preprocollagen) 2) Hydroxylation of proline and lysine residues 3) Glycosylation and formation of procollagen
185
Steps in collagen synthesis that take place outside fibroblasts
1) Proteolytic processing (formation of tropocollagen by cleavage of disulfide-rich regions of procollagen) 2) Cross-linking
186
Structure of preprocollagen (collagen alpha chains)
Gly-X-Y (Gly is glycine; X and Y are proline or lysine)
187
Best reflects collagen synthesis
Glycine
188
Collagen is 1/3 ___ (amino acid)
Glycine
189
What step in collagen synthesis requires Vitamin C?
Hydroxylation of specific proline and lysine residues
190
Problems forming triple helix of 3 collagen _ chains (glycosylation and formation of procollagen)
Osteogenesis imperfecta
191
Problems with collagen cross-linking lead to
1) Ehler-Danlos 2) Menkes disease
192
AKA Brittle bone disease
Osteogenesis imperfecta
193
Why is there hearing loss in osteogenesis imperfecta
Abnormal ossicles
194
Faulty collagen synthesis causing hyperextensible skin, tendency to bleed (easy bruising), and hypermobile joints
Ehlers-Danlos syndrome
195
MC type of Ehlers-Danlos syndrome
Hypermobility type
196
Classical type of Ehlers-Danlos is due to mutation of what collagen type
V
197
Vascular type (vascular and organ rupture) of Ehlers-Danlos is due to deficiency of
Type III collagen
198
X-linked recessive connective tissue disease caused by impaired copper absorption and transport due to defective ATP7A
Menkes disease
199
Menkes disease is associated with decreased activity of what enzyme
Lysyl oxidase (copper is a necessary cofactor)
200
Elastin is rich in what amino acids
1) Proline 2) Glycine 3) Lysine
201
Where does elastin cross-linking take place
Extracellularly
202
Where is elastin found
Skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava (connect vertebrae)
203
Elastin is broken down by elastase, which is normally inhibited by
_1-antitrypsin
204
A glycoprotein that forms a sheath around elastin
Fibrillin (defective in Marfan syndrome)
205
Wrinkles of aging are due to decreased production of what proteins
Collagen and elastin
206
Steps in PCR
1) Denaturation 2) Annealing 3) Elongation
207
Denaturating agent in PCR that generates 2 separate strands
Heating
208
Anneal to a specific sequence on each strand to be amplified during cooling
DNA primers
209
Replicates the DNA sequence following each primer
Heat-stable DNA polymerase
210
Used for size separation of PCR products (smaller molecules travel further) and compared against DNA ladder
Agarose gel electrophoresis
211
Blotting procedures and corresponding biomolecule electrophoresed
[SNoW DRoP] Southern: DNA, Northern: RNA, Western: Protein
212
Blotting procedure used as confirmatory test for HIV after a (+) ELISA
Western blot
213
Blotting procedure used to identify DNA-binding proteins such as transcription factors
Southwestern blot
214
Used to detect the presence of either a specific antigen or a specific antibody in a patient's blood sample
ELISA
215
Direct vs Indirect ELISA: Uses a test antibody to see if a specific antigen is present
Direct
216
Direct vs Indirect ELISA: Uses either a test antigen or antibody to see if a specific antibody or antigen, respectively, is present
Indirect
217
Karyotyping makes use of chromosomes at what phase of the cell cycle
Metaphase
218
Karyotyping can be performed on what samples
Blood, bone marrow, amniotic fluid, or placental tissue
219
When is FISH used instead of karyotyping
When deletion is too small to be visualized by karyotype
220
Fluorescence vs no fluorescence: Gene is absent/deleted
No fluorescence
221
Production of a recombinant DNA molecule that is self-perpetuating
Cloning
222
RNA used in cloning
mRNA
223
Cloned DNA (cDNA) lacks what part of the gene
Introns
224
Can be used to study a gene whose deletion causes embryonic death
Cre-lox system
225
Both alleles contribute to the phenotype of the heterozygote, e.g. Blood groups A, B, AB
Codominance
226
Phenotype varies among individuals with same genotype, e.g. more severe in some and less severe in others
Variable expressivity
227
Not all individuals with a mutant genotype show the mutant phenotype, e.g. BRCA1 mutations do not always result in breast or ovarian CA
Incomplete penetrance
228
One gene contributes to multiple phenotypic effects
Pleiotropy
229
Increased severity or earlier onset of disease in succeeding generations
Anticipation
230
A mosaicism and is due to mutation affecting G-protein signaling
McCune-Albright syndrome
231
2 syndromes that are both due to mutation or deletion of genes on chromosome 15
1) Prader-Willi 2) Angelman
232
Maternal imprinting: gene from mom is normally silent and Paternal gene is deleted/ mutated
Prader-Willi
233
Paternal imprinting: gene from dad is normally silent and Maternal gene is deleted/mutated
Angelman
234
Mode of inheritance: Often due to defects in structural genes. Many generations, both male and female, affected.
Autosomal dominant
235
to diagnosis
Autosomal dominant
236
Mode of inheritance: Often due to enzyme deficiencies. Usually seen in only 1 generation.
Autosomal recessive
237
T/F Autosomal recessive diseases are commonly more severe than dominant disorders
T
238
Mode of inheritance: Increased risk in consanguineous families
Autosomal recessive
239
Mode of inheritance: Sons of heterozygous mothers have a 50% chance of being affected. No male-to-male transmission. Skips generations.
X-linked recessive
240
Mode of inheritance: Transmitted through both parents. Mothers transmit to 50% of daughters and sons; fathers transmit to all daughters but no sons.
X-linked dominant
241
Disease with X-linked dominant inheritance
Hypophosphatemic rickets, formerly known as vitamin D-resistant rickets
242
Mode of inheritance: Transmitted only through the mother. All offspring of affected females may show signs of disease
Mitochondrial inheritance
243
Muscle biopsy of mitochondrial myopathies often shows
Ragged red fibers
244
Autosomal dominant diseases
1) Autosomal dominant polycystic kidney disease (ADPKD) 2) FAP 3) Familial hypercholesterolemia 4) Hereditary hemorrhagic telangiectasia 5) Hereditary spherocytosis 6) Huntington disease 7) Li-Fraumeni syndrome 8) Marfan 9) MEN 10) NF 1 (von Recklinghausen) and 2 11) Tuberous sclerosis 12) von Hippel-Lindau
245
Colon becomes covered with adenomatous polyps after puberty, which may progress to colon cancer unless colon is resected
FAP
246
Severe atherosclerotic disease early in life, corneal arcus, tendon xanthomas (classically in Achilles tendon)
Familial hypercholesterolemia
247
Elevated LDL in familial hypercholesterolemia is due to
Defective or absent LDL receptor
248
Inherited disorder of blood vessels; branching skin lesions (telangiectasias), recurrent epistaxis, skin discolorations, arteriovenous malformations (AVMs), GI bleeding, hematuria
Hereditary hemorrhagic telangiectasia
249
Hereditary hemorrhagic telangiectasia is aka
Osler-Weber-Rendu syndrome
250
Hereditary spherocytosis is due to defect of
1) Spectrin 2) Ankyrin
251
Treatment for hereditary spherocytosis
Splenectomy
252
Depression, progressive dementia, choreiform movements, and caudate atrophy
Huntington disease
253
Neurotransmitter derrangement in Huntington
Increased dopamine, decreased GABA, decreased ACh
254
CAG repeat disorder
Huntington disease
255
Multiple malignancies at an early agar, aka SBLA cancer (sarcoma, breast, leukaemia, adrenal gland)
Li-Fraumeni syndrome
256
Pectus excavatum, hypermobile joints, and long, tapering fingers and toes (arachnodactyly)
Marfan
257
Cystic medial necrosis of aorta > aortic incompetence and dissecting aortic aneurysms
Marfan
258
Floppy mitral valve
Marfan
259
Direction of lens subluxation in Marfan
Upward and temporally
260
Optic gliomas, pheochromocytomas, Lisch nodules
NF1
261
What are Lisch nodules
Pigmented iris hamartomas
262
Bilateral acoustic schwannomas, juvenile cataracts, meningiomas, and ependymomas
NF2
263
Neurocutaneous disorder with multi-organ system involvement, characterized by numerous benign hamartomas
Tuberous sclerosis
264
Development of numerous tumors, both benign and malignant
von Hippel-Lindau disease
265
MC gene mutated in ADPKD
PKD1
266
Gene mutated in FAP
APC
267
Abnormal in Li-Fraumeni syndrome
TP53
268
Gene mutated in Marfan
FBN1
269
Gene mutated in MEN 1
MEN1
270
Gene mutated in MEN 2A and 2B
RET
271
Gene deleted in von Hippel-Lindau disease
VHL gene (tumor suppressor)
272
Deleted in cystic fibrosis
Phe508
273
Chromosome: ADPKD
16 [POLYCYSTIC KIDNEY = 16]
274
Chromosome: FAP
5q [POLYP = 5]
275
Chromosome: Huntington
4 [Hunting 4 food]
276
Chromosome: Marfan
15 [MARFAN SYNDROME = 15 including the space]
277
Chromosome: NF1
17 [VON RECKLINGHAUSEN = 17]
278
Chromosome: NF2
22
279
Chromosome: von Hippel-Lindau disease
3 [VON HIPPEL LINDAU = 3 words]
280
Autosomal recessive diseases
Albinism, autosomal recessive polycystic kidney disease (ARPKD), cystic fibrosis, glycogen storage diseases, hemochromatosis, Kartagener syndrome, mucopolysaccharidoses (except Hunter syndrome), phenylketonuria, sickle cell anemia, sphingolipidoses (except Fabry disease), thalassemias, Wilson disease
281
Most common lethal genetic disease in Caucasian population
Cystic fibrosis
282
Concentration of chloride in sweat that is diagnostic of CF
>60 mEq/L
283
GI complication seen in newborns with CF
Meconium ileus
284
T/F Patients with CF may have infertility
T, male absence of vas deferens, female amenorrhea and abnormally thick cervical mucus
285
Vitamin deficiency in CF
Fat-soluble vitamins (ADEK)
286
Treatment for CF
N-acetylcysteine (cleaves disulphide bonds within mucus glycoproteins
287
Gene defect in cystic fibrosis
CFTR
288
What does the CFTR gene encode
ATP-gated chloride channel that secretes chloride in the lungs and GIT, and reabsorbs chloride in sweat glands resulting in a compensatory increase in Na reabsorption
289
Chromosome: Cystic fibrosis
7
290
X-linked disorder typically due to frameshift (deletions, duplications, or nonsense) mutations
Duchenne muscular dystrophy
291
Gene deleted in Duchenne muscular dystrophy
Dystrophin gene (DMD)
292
The largest protein-coding human gene
Dystrophin gene (DMD)
293
Progress of muscle weakness in Duchenne muscular dystrophy
Pelvic girdle > superiorly
294
Pseudohypertrophy of calf muscles in Duchenne muscular dystrophy is due to
Fibrofatty replacement of muscle
295
Maneuver: Patients use upper extremities to help them stand up
Gower maneuver
296
Gait in Duchenne muscular dystrophy
Waddling
297
Onset of Duchenne muscular dystrophy
Less than 5 y/o
298
Preliminary diagnosis of Duchenne muscular dystrophy
Elevated CPK and aldolase
299
Confirmatory diagnosis of Duchenne muscular dystrophy
Western blot and muscle biopsy
300
X-linked disorder typically due to non-frameshift insertions in dystrophin gene
Becker
301
Becker vs Duchenne: More severe
Duchenne
302
Onset of Becker
Adolescence or adulthood
303
2nd most common cause of genetic intellectual disability (after Down syndrome)
Fragile X syndrome
304
CGG repeat disorder
Fragile X syndrome
305
Findings in Fragile X syndrome
Xtra large testes, jaw, and ears
306
Gene affected in Fragile X syndrome
FMR1
307
Cardiac abnormality associated with Fragile X syndrome
Mitral valve prolapse
308
GAA repeat disorder
Friedreich ataxia
309
CTG repeat disorder
Myotonic dystrophy
310
3 autosomal trisomies
13 [Puberty] Patau; 18 [Elect] Edward; 21 [Drink] Down
311
Gap between 1st 2 toe
Down
312
Brushfield spots
Down
313
Rocker- bottom feet
Edward and Patau
314
Micrognathia
Edward
315
Microphthalmia and microcephaly
Patau
316
Cleft liP/Palate
Patau
317
Early-onset Alzheimer disease
Chrom 21 codes for amyloid precursor protein
318
Increased risk of ALL and AML
Down
319
95% of cases of Down syndrome is due to
Meiotic nondisjunction
320
Clenched hands with overlapping fingers
Edward
321
2nd most common trisomy resulting in live birth
Edward
322
Most common viable chromosomal disorder
Down
323
Most common cause of genetic intellectual disability
Down
324
Chromosome: Cri-du-chat
5, short arm (p)
325
Chromosome: Wilms tumor
11
326
Chromosome: DiGeorge
22 (22q11)
327
X-chromosome
1) Fragile X 2) X-linked agammaglobulinemia 3) Klinefelter
328
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
Robertsonian translocation
329
Cardiac abnormality in Cri du chat
VSD
330
Elfin facies; extreme friendliness with strangers
Williams syndrome
331
Chromosome: Williams syndrome
7
332
Aberrant development of 3rd and 4th branchial pouches
DiGeorge (thymic, parathyroid, cardiac defects; Velocardial syndrome (palate, facial, cardiac defects)
333
All water-soluble vitamins wash out easily from body except ___
B12 and folate (stored in liver)
334
Clenched hands with overlapping fingers
Edward
335
Uses ATP to add high-energy phosphate group onto substrate
Kinase
336
Adds inorganic phosphate onto substrate without using ATP
Phosphorylase
337
Removes phosphate group from substrate
Phosphatase
338
Catalyzes oxidation-reduction reactions
Dehydrogenase
339
Adds hydroxyl group (_OH) onto substrate
Hydroxylase
340
Transfers CO2 groups with the help of biotin
Carboxylase
341
Relocates a functional group within a molecule
Mutase
342
Rate-limiting enzyme: Glycolysis
PFK-1
343
Rate-limiting enzyme: Gluconeogenesis
Fructose-1,6-bisphosphatase
344
Rate-limiting enzyme: TCA cycle
Isocitrate dehydrogenase
345
Rate-limiting enzyme: Glycogenesis
Glycogen synthase
346
Rate-limiting enzyme: Glycogenolysis
Glycogen phosphorylase
347
Rate-limiting enzyme: HMP shunt
Glucose-6-phosphate dehydrogenase (G6PD)
348
Rate-limiting enzyme: De novo pyrimidine synthesis
Carbamoyl phosphate synthetase II
349
Rate-limiting enzyme: De novo purine synthesis
Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
350
Rate-limiting enzyme: Urea cycle
Carbamoyl phosphate synthetase I
351
Rate-limiting enzyme: Fatty acid synthesis
Acetyl-CoA carboxylase (ACC)
352
Rate-limiting enzyme: Fatty acid oxidation
Carnitine acyltransferase I
353
Rate-limiting enzyme: Ketogenesis
HMG-CoA synthase
354
Rate-limiting enzyme: Cholesterol synthesis
HMG-CoA reductase
355
Rate-limiting enzyme: Heme synthesis
ALA synthase
356
Regulators of enzyme: PFK-1
AMP _, fructose-2,6-bisphosphate _; ATP _, citrate _
357
Regulators of enzyme: Fructose-1,6-bisphosphatase
ATP _, acetyl-CoA _; AMP _, fructose-2,6-bisphosphate _
358
Regulators of enzyme: Isocitrate dehydrogenase
ADP_; ATP _, NADH _
359
Regulators of enzyme: Glycogen synthase
Glucose-6-phosphate _, insulin _, cortisol _; Epinephrine _, glucagon _
360
Regulators of enzyme: Glycogen phosphorylase
Epinephrine _, glucagon _, AMP _; Glucose-6-phosphate _, insulin _, ATP _
361
Regulators of enzyme: Glucose-6-phosphate dehydrogenase (G6PD)
NADP+ _; NADPH _
362
Regulators of enzyme: Carbamoyl phosphate synthetase II
ATP _; UTP _
363
Regulators of enzyme: Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
AMP _, inosine monophosphate (IMP) _, GMP _
364
Regulators of enzyme: Carbamoyl phosphate synthetase I
N-acetylglutamate _
365
Regulators of enzyme: Acetyl-CoA carboxylase (ACC)
Insulin _, citrate _; Glucagon _, palmitoyl-CoA _
366
Regulators of enzyme: Carnitine acyltransferase I
Malonyl-CoA _
367
Regulators of enzyme: HMG-CoA reductase
Insulin _, thyroxine _; Glucagon _, cholesterol _
368
Enzyme deficient in mild galactosemia
Galactokinase
369
Enzyme deficient in severe galactosemia
Galactose-1-phosphate uridyltransferase
370
Catalyzes INTERCONVERSION of glucose-1-phosphate and glucose-6-phosphate
Hexokinase/glucokinase
371
Enzyme deficient in von Gierke
Glucose-6-phosphatase (INTERCONVERSION between glucose and glucose-6-phosphate)
372
Glucose-6-phosphate dehydrogenase, catalyzes what
Glucose-6-phosphate to 6-phosphogluconolactone
373
Require thiamine as a cofactor
1) Transketolase 2) Pyruvate dehydrogenase 3) _-ketoglutarate dehydrogenase
374
Aerobic metabolism of glucose produces ___ net ATP via malate-aspartate shuttle
32
375
Malate-aspartate shuttle is found in what organs
Heart and liver
376
Aerobic metabolism of glucose produces ___ net ATP via glycerol-3-phosphate shuttle
30
377
Glycerol-3-phosphate shuttle is found in what organ
Muscle
378
Anaerobic glycolysis produces ___ net ATP per glucose molecule
2
379
___ causes glycolysis to produce zero net ATP
Arsenic
380
Carrier molecule: Phosphoryl groups
ATP
381
Carrier molecule: Electrons
NADH, NADPH, FADH2
382
Carrier molecule: Acyl groups
CoA, lipoamide
383
Carrier molecule: CO2
Biotin
384
Carrier molecule: Aldehydes
TPP
385
Carrier molecule: 1-carbon units
Tetrahydrofolates
386
NAD+ is from what vitamin
B3
387
FAD+ is from what vitamin
B2
388
Electron acceptor that is generally used in catabolic processes to carry reducing equivalents away
NAD+
389
Electron acceptor that is used in anabolic processes (steroid and fatty acid synthesis) as a supply of reducing equivalents
NADPH
390
NADPH is a product of the ___ shunt
HMP
391
NADPH is used in (4)
1) Anabolic processes 2) Respiratory burst 3) Cytochrome P-450 system 4) Glutathione reductase
392
1st step of glycolysis which also serves as the 1st step of glycogen synthesis in the liver
Phosphorylation of glucose to yield glucose-6-phosphate
393
Phosphorylation of glucose to yield glucose-6-phosphate is catalyzed by
Hexokinase/glucokinase
394
Hexokinase vs glucokinase: Induced by insulin
Glucokinase
395
Hexokinase vs glucokinase: Feedback-inhibited by glucose-6-phosphate
Hexokinase
396
Hexokinase vs glucokinase: Gene mutation associated with maturity-onset diabetes of the young (MODY)
Glucokinase
397
Steps in glycolysis that require ATP
1) Gluc > Gluc6P by hexokinase/glucokinase 2) Fruc6P > Fruc1,6BP
398
Steps in glycolysis that produce ATP
1) 1,3BPG > 3PG via phosphoglycerate kinase 2) PEP > pyruvate via pyruvate kinase
399
___ and ___ are the same bifunctional enzyme whose function is reversed by phosphorylation by protein kinase A
FBPase-2 (fructose bisphosphatase-2) and PFK-2
400
FBPase-2 vs PFK-2, active in fasting state
FBPase-2 (Fruc2,6BP is converted to Fruc6P > more glycolysis, less gluconeogenesis)
401
FBPase-2 vs PFK-2, active in fed state
PFK-2 (Fruc6P is converted to Fruc2,6BP instead of Fruc1,6BP > less glycolysis, more gluconeogenesis
402
Mitochondrial enzyme complex linking glycolysis and TCA cycle
Pyruvate dehydrogenase complex
403
Pyruvate dehydrogenase complex is active in, fed vs fasting state
Fed
404
Pyruvate dehydrogenase complex is activated vs inhibited by exercise
Activated
405
Pyruvate dehydrogenase complex is similar to the ___ (same cofactors, similar substrate and action) of the TCA cycle
_-ketoglutarate dehydrogenase complex
406
Pyruvate dehydrogenase complex, reaction catalyzed
_-ketoglutarate > succinyl-CoA
407
Inhibits lipoic acid
Arsenic
408
Findings in arsenic poisoning
Vomiting, rice-water stools, garlic breath
409
Treatment for pyruvate dehydrogenase complex deficiency
Inc intake of ketogenic nutrients
410
The only purely ketogenic amino acids
Lysine, Leucine [Think onLy pureLy ketogenic]
411
Pyruvate metabolic pathway: Carries amino groups to the liver from muscle
Alanine of alanine aminotransferase (cofactor: B6)
412
Pyruvate metabolic pathway: Oxaloacetate can replenish TCA cycle or be used in gluconeogenesis
Pyruvate carboxylase (cofactor: biotin)
413
Pyruvate metabolic pathway: Transition from glycolysis to the TCA cycle
Pyruvate dehydrogenase (co-factors: B1, B2, B3, B5, lipoic acid)
414
Pyruvate metabolic pathway: End of anaerobic glycolysis (major pathway in RBCs, WBCs, kidney medulla, lens, testes, and cornea)
Lactic acid dehydrogenase (c0-factor: B3)
415
Products of TCA cycle
1) 3 NADH 2) 2 CO2 3) 1 FADH2 4) 1 high-energy compound (GTP)
416
Electrons from glycolysis enters the mitochondria via
1) Malate-aspartate shuttle 2) Glycerol-3-phosphate shuttle
417
FADH2 from glycolysis are transferred to what complex of the ETC
II
418
How many ATP are produced via ATP synthase
1.5
419
Inhibit the ETC by causing a decrease in proton gradient and block of ATP synthesis
Electron transport inhibitors
420
Inhibit the ETC by causing an increase in proton gradient
ATP synthase inhibitors
421
Increases mitochondrial membrane permeability, causing a decrease in proton gradient and increase in O2 consumption; ATP synthesis stops but ETC continues
Uncoupling agents
422
ATP synthase inhibitor of the ETC
Oligomycin
423
What are the uncoupling agents
1) 2,4-dinitrophenol 2) Aspirin 3) Thermogenin
424
Irreversible enzymes of gluconeogenesis
1) Pyruvate carboxylase 2) PEP carboxykinase 3) Fructose-1,6- bisphosphatase 4) Glucose-6-phosphatase [Think Pathway Produces Fresh Glucose]
425
Irreversible enzyme of gluconeogenesis seen in the mitochondria
Pyruvate carboxylase
426
Irreversible enzymes of gluconeogenesis seen in the cytosol
1) PEP carboxykinase 2) Fructose-1,6-bisphosphatase
427
Irreversible enzyme of gluconeogenesis seen in the ER of liver cells
Glucose-6-phosphatase
428
Pyruvate > oxaloacetate
Pyruvate carboxylase
429
Oxaloacetate > PEP
PEP carboxykinase
430
Fructose-1,6-bisphosphate > fructose-6-phosphate
Fructose-1,6- bisphosphatase
431
Glucose-6-phosphate> glucose
Glucose-6-phosphatase
432
Gluconeogenesis occurs primarily in the
Mitochondria and cytosol of liver (other sites: kidney, intestinal epithelium)
433
Metabolic process that serves to maintain euglycemia in fasting
Gluconeogenesis
434
Muscle cannot participate in gluconeogenesis because it lacks
Glucose-6-phosphatase
435
Odd-chain vs even-chain fatty acids: Source of substrate for gluconeogenesis
Odd-chain
436
Even-chain fatty acids cannot produce new glucose because ___
They yield only acetyl-CoA equivalents
437
Odd-chain fatty acids yield ___ during metabolism, which can enter the TCA cycle and undergo gluconeogenesis
1 propionyl-CoA
438
1 propionyl-CoA from odd-chain fatty acids can enter the TCA cycle as
Succinyl-CoA
439
Provides a source of NADPH from abundantly available glucose-6-P
HMP shunt (pentose phosphate pathway)
440
NADPH is required for biosynthesis of (3)
1) Fatty acids 2) Cholesterol 3) Nucleotides (ribose) 4) Glycolytic intermediates
441
2 phases of HMP shunt
1) Oxidative 2) Non-oxidative
442
HMP shunt occurs in
Cytoplasm
443
Number of ATP used and produced in HMP shunt
NONE
444
Organs where HMP shunt can be found
1) Lactating mammary glands 2) Liver 3) Adrenal cortex 4) RBCs
445
Site of fatty acid or steroid synthesis
Adrenal cortex
446
HMP reaction that is irreversible
Oxidative reaction: G6PD
447
HMP reaction that is reversible
Non-oxidative: Phosphopentose isomerase, transketolases
448
Most common human enzyme deficiency; more prevalent in blacks
G6PD deficiency
449
Inheritance pattern of G6PD deficiency
X-linked recessive
450
G6PD deficiency increases resistance against what infection
Malaria
451
RBCs contain ___ in patients with G6PD deficiency
Heinz bodies (denatured/precipitated Hgb due to oxidative stress)
452
RBCs appear as ___ in patients with G6PD
Bite cells, due to phagocytic removal of Heinz bodies by splenic macrophages
453
Metabolic disorder resulting from deficiency of fructokinase
Essential fructosuria
454
Essential fructosuria is a benign, asymptomatic condition because
Fructose is not trapped in cells
455
Fructose intolerance is a hereditary deficiency of ___
Aldolase B
456
In fructose intolerance, ___ accumulates
Fructose-1-phosphate
457
Glucose level in fructose intolerance
Hypoglycemia
458
Why is there hypoglycemia in fructose intolerance
Decrease in available phosphate > inhibition of glycogenolysis and gluconeogenesis
459
Symptoms of fructose intolerance present following consumption of ___
Fruit, juice, or honey
460
T/F In fructose intolerance, urine dipstick will be positive
F
461
T/F In fructose intolerance, reducing sugar can be detected in the urine
T
462
Nonspecific test for inborn errors of carbohydrate metabolism
Detection of reducing sugars in urine
463
Treatment for fructose intolerance
Decrease intake of both fructose and sucrose (glucose + fructose)
464
In galactokinase deficiency, ___ accumulates if galactose is present in diet
Galactitol
465
Important finding in galactokinase deficiency that manifests as failure to track objects or develop a social smile
Infantile cataracts
466
Classic galactosemia is due to deficiency of
G1PUT
467
Classic galactosemia can lead to ___ sepsis in neonates
E. coli
468
Treatment for classic galactosemia
Exclude galactose and lactose (galactose + glucose) from the diet
469
Galactose is converted to galactitol (its alcohol counterpart) by what enzyme
Aldose reductase
470
Glucose is converted to sorbitol (its alcohol counterpart) by what enzyme
Aldose reductase
471
Some tissues convert sorbitol to fructose using ___; tissues with an insufficient amount of this enzyme are at risk for intracellular sorbitol accumulation, causing osmotic damage
Sorbitol dehydrogenase
472
BOTH aldose reductase and sorbitol dehydrogenase are found in what organs
1) Liver 2) Ovaries 3) Seminal vesicles
473
Organs/cells that have only aldose reductase
1) Schwann cells 2) Retina 3) Kidneys
474
Organ that has both aldose reductase and sorbitol dehydrogenase but PRIMARILY aldose reductase
Lens
475
Lactose intolerance characterized by an age-dependent decline after childhood, common in people of Asian, African, or Native American descent
Primary lactose intolerance
476
Lactose intolerance characterized by loss of brush border due to gastroenteritis (rotavirus), autoimmune disease, etc
Secondary lactose intolerance
477
Rare form of lactose deficiency and is due to defective gene
Congenital
478
Amino acids found in proteins
L-amino acids
479
Essential amino acids
[PVT TIM HALL always Argues but never TYRes] 1) Phenylalanine 2) Valine 3) Threonine 4) Isoleucine 5) Methionine 6) Histidine 7) Arginine 8) Lysine 9) Leucine
480
Amino acids that are both glucogenic and ketogenic
[KiLL PITT] 1) Phenylalanine 2) Isoleucine 3) Tryptophan 4) Threonine
481
Acidic amino acids
1) Aspartic acid 2) Glutamic acid
482
Basic amino acids
Basic HAL 1) Histidine 2) Arginine 3) Lysine
483
Most basic amino acid
Arginine
484
Amino acids that are negatively charged at body pH
Acidic a.a.
485
Amino acids that have no charge at body pH
Basic a.a.
486
Amino acids that are required during period of growth
1) Arginine 2) Histidine
487
Conversion of alanine to glucose and vice versa; an intermediate in amino acid catabolism
Cahill cycle
488
Conversion of lactate to glucose and vice versa; an intermediate in amino acid catabolism
Cori cycle
489
Hyperammonemia results in excess NH4+ (ammonium ion), which depletes what substrate of the TCA cycle
_-ketoglutarate
490
Given to patients with hyperammonemia to acidify the GI tract and trap NH4+ for excretion
Lactulose
491
Given in patients with hyperammonemia to decrease colonic ammoniagenic bacteria
Rifaximin
492
___ or ___ may be given to patients with hyperammonemia (both of which bind amino acid and lead to excretion)
Benzoate or phenylbutyrate
493
Required cofactor for carbamoyl phosphate synthetase I of urea cycle, the deficiency of which leads to hyperammonemia
N-acetylglutamate synthase deficiency
494
Most common urea cycle disorder
Ornithine transcarbamylase deficiency
495
The only X-linked recessive urea cycle disorder
Ornithine transcarbamylase deficiency
496
Ornithine transcarbamylase deficiency leads to excess ___ which is converted to orotic acid (pyrimidine synthesis)
Carbamoyl phosphate
497
In contrast to orotic aciduria, ornithine transcarbamylase does not present with
Megaloblastic anemia
498
Glycine derivatives
1) Porphyrin 2) Heme
499
Glutamate derivatives
1) GABA 2) Glutathione
500
Arginine derivatives
1) NO 2) Creatine 3) Urea
