BIOCHEMISTRY USMLE STEP 1 STUDY KIT
WITH COMPLETE QUESTIONS AND
ANSWERS
MOA of 6-MP and Azathioprine (and use) Correct Answer inhibit
de novo purine synthesis
tx: leukemia, immune dzs (RA, IBD)
inhibit dihydrofolate reductase (DHFR) Correct Answer
methotrexate (MTX) in humans
trimethoprim (TMP) in bacteria
pyrimethamine in protozoa
prevents pyrimidine synthesis (dUMP --> dTMP)
folate is supplemental for which drugs and why? Correct Answer
5-FU > increase potency
MTX > reduce side effects
major cause of AR SCID and why Correct Answer adenosine
deaminase (ADA) deficiency
prevents purine salvage, affects cells that need to divide a lot
(immune cells > reduces lymphocyte count)
pathophys of adenosine deaminase (ADA) deficiency Correct
Answer buildup of adenosine (bc low ADA prevents degradation)
> feedback inhibition of ribonucleotide reductase --I DNA
,synthesis --> dec lymphocyte count and causes
immunodeficiency (SCID)
purine salvage enzyme & function Correct Answer HGPRT
Recycles:
hypoxanthine > IMP
guanine > GMP
key enzymes of purine degradation Correct Answer ADA
(adenosine > inosine)
XO (hypoxanthine > xanthine > uric acid)
purine degradation overview Correct Answer 1. removal of
phosphate from nucleotide
2. removal of sugar from nucleoside
3. convert free bases (guanine & hypoxanthine) to xanthine by
xanthine oxidase (XO)
4. xanthine > uric acid by xanthine oxidase (XO)
5. uric acid to urine
defective purine salvage due to absent HGPRT (dz name) Correct
Answer Lesch-Nyhan syndrome
symptoms of Lesch-Nyhan syndrome Correct Answer HGPRT
deficiency:
Hyperuricemia
Gout
Pissed off (aggression, self-mutilation)
Retardation
dysTonia
defective purine salvage due to absent HGPRT --> excessive uric
acid production and de novo purine synthesis
function of HGPRT Correct Answer purine salvage (adds sugar/P
to free base)
converts hypoxanthine + PRPP --> IMP
converts guanine + PRPP --> GMP
inheritance of Lesch-Nyhan syndrome Correct Answer X-linked
recessive
treatment of Lesch-Nyhan syndrome Correct Answer XO-
inhibitors: allopurinol or febuxostat (2nd line)
reduce uric acid causing hyperuricemia and sxs
XO-inhibitors reduces the efficacy of which drugs Correct Answer
drugs that look like purines (6-MP, leukemia tx)
AA encoded by only 1 codon Correct Answer AUG -->
methionine
UGG --> tryptophan
create single or double stranded breaks in DNA helix to add or
remove supercoils Correct Answer DNA topoisomerases
unwinds DNA template at replication fork Correct Answer
helicase
"helicase has the most fun bc it spends all day unzipping genes!"
bonds helicase breaks Correct Answer H-bonds only
, inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and
topoisomerase IV Correct Answer fluoroquinolones
direction of DNA and RNA synthesis & protein synthesis &
implications Correct Answer 5' --> 3'
N' --> C'
drugs (AZT) can target triphosphate bond @ 3' hydoxyl
found in prokaryotes only, has 5' --> 3' synthesis and 3' --> 5'
exonuclease proofreading Correct Answer DNA pol III
makes RNA primer on which DNA polymerase III can initiate
replication Correct Answer Primase
found in prokaryotes only, degrades RNA primer with 5' --> 3'
exonuclease and replaces in with 5' --> 3' DNA synthesis Correct
Answer DNA pol I
also has has 5' --> 3' synthesis and 3' --> 5' exonuclease
proofreading like DNA pol III
joins Okazaki fragments Correct Answer DNA ligase
catalyzes phosphodiester bond formation within a strand of
dsDNA
telomerase Correct Answer RNA-dependent DNA polymerase
that adds DNA to 3' ends of chromosomes to avoid loss of genetic
material with every duplication
euks only
only in cells that divide a lot (stem cells, immune cells)
transition point mutation Correct Answer purine to purine
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