Biochemistry USMLE step 1 Exam Questions with Correct Verified Answers Latest Update (2024/2025) Guaranteed Pass

Biochemistry USMLE step 1 Exam Questions with Correct Verified Answers Latest Update (2024/2025) Guaranteed Pass 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 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) 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 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 Found in prokaryotes only, degrades RNA primer with 5' -- 3' exonuclease and replaces in with 5' -- 3' DNA synthesis - ANS DNA pol I Also has 5' -- 3' synthesis and 3' -- 5' exonuclease proofreading like DNA pol III Joins Okazaki fragments - ANS DNA ligase Catalyzes phosphodiester bond formation within a strand of dsdna Telomerase - ANS 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 - ANS purine to purine Pyrimidine to pyrimidine Transversion point mutation - ANS purine to pyrimidine Pyrimidine to purine