Biochemistry USMLE step 1 Exam
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Inhibit dihydrofolate reductase (DHFR) - ANS ✓methotrexate (MTX) in
humans
Trimethoprim (TMP) in bacteria
Pyrimethamine in protozoa
Prevents pyrimidine synthesis (dump --> dtmp)
Folate is supplemental for which drugs and why? - ANS ✓5-FU >
increase potency
MTX > reduce side effects
Major cause of AR SCID and why - ANS ✓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 - ANS ✓buildup of
adenosine (bc low ADA prevents degradation) > feedback inhibition of
Biochemistry USMLE step 1
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USMLE
ribonucleotide reductase --I DNA synthesis --> dec lymphocyte count and
causes immunodeficiency (SCID)
Purine salvage enzyme & function - ANS ✓HGPRT
Recycles:
Hypoxanthine > IMP
Guanine > GMP
Key enzymes of purine degradation - ANS ✓ADA (adenosine > inosine)
XO (hypoxanthine > xanthine > uric acid)
Purine degradation overview - ANS ✓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) - ANS
✓Lesch-Nyhan syndrome
Symptoms of Lesch-Nyhan syndrome - ANS ✓HGPRT deficiency:
Hyperuricemia
Gout
Pissed off (aggression, self-mutilation)
Biochemistry USMLE step 1
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USMLE
Retardation
Dystonia
Young male
Gout
Aggression, self-mutilation
Intellectual disability
Dystonia - ANS ✓Lesch-Nyhan syndrome
Defective purine salvage due to absent HGPRT --> excessive uric acid
production and de novo purine synthesis
Function of HGPRT - ANS ✓purine salvage (adds sugar/P to free base)
Converts hypoxanthine + PRPP --> IMP
Converts guanine + PRPP --> GMP
Inheritance of Lesch-Nyhan syndrome - ANS ✓X-linked recessive
Treatment of Lesch-Nyhan syndrome - ANS ✓XO-inhibitors: allopurinol
or febuxostat (2nd line)
Reduce uric acid causing hyperuricemia and sxs
XO-inhibitors reduces the efficacy of which drugs - ANS ✓drugs that
look like purines (6-MP, leukemia tx)
AA encoded by only 1 codon - ANS ✓AUG --> methionine
Biochemistry USMLE step 1
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USMLE
UGG --> tryptophan
Create single or double stranded breaks in DNA helix to add or
remove supercoils - ANS ✓DNA topoisomerases
Unwinds DNA template at replication fork - ANS ✓helicase
"helicase has the most fun bc it spends all day unzipping genes!"
Bonds helicase breaks - ANS ✓H-bonds only
Inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and
topoisomerase IV - ANS ✓fluoroquinolones
Direction of DNA and RNA synthesis & protein synthesis &
implications - ANS ✓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 - ANS ✓DNA pol III
Makes RNA primer on which DNA polymerase III can initiate
replication - ANS ✓Primase
Biochemistry USMLE step 1
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