USMLE Biochemistry Syllabus

Biochemistry syllabus — full chapter and topic list

Expand any chapter to see its topics and sub-topics. This is the whole examinable outline for Biochemistry in USMLE, not a summary of it.

1. 1

   Molecular Biology

   3 topics

   • DNA replication
   • RNA transcription
   • Protein translation
2. 2

   Genetics

   3 topics

   • Mendelian genetics
   • Genetic mutations
   • Gene therapy
3. 3

   Metabolism

   3 topics

   • Carbohydrate metabolism
   • Lipid metabolism
   • Amino acid metabolism

Biochemistry flashcards for USMLE

19 of 51 cards from the Biochemistry deck — real questions with worked answers.

1. In which direction does DNA polymerase synthesize a new strand, and which end does it add nucleotides to?

   It synthesizes only in the $5' \to 3'$ direction, adding incoming dNTPs to the free $3'$-hydroxyl ($3'\text{-OH}$) of the growing strand.

2. Why is DNA replication described as semiconservative?

   Each daughter duplex retains one parental (template) strand and one newly synthesized strand, as demonstrated by the Meselson-Stahl experiment.

3. What are Okazaki fragments and on which strand do they form?

   Short DNA segments synthesized discontinuously on the lagging strand (in the $5' \to 3'$ direction away from the fork); they are later joined by DNA ligase.

4. Which enzyme relieves supercoiling ahead of the replication fork, and which class is the target of fluoroquinolones?

   Topoisomerases (DNA gyrase in bacteria = topoisomerase II). Fluoroquinolones inhibit bacterial topoisomerase II and IV.

5. What is the function of primase in DNA replication?

   Primase (an RNA polymerase) synthesizes a short RNA primer providing the free $3'\text{-OH}$ that DNA polymerase requires to begin synthesis.

6. Which eukaryotic DNA polymerases replicate the leading and lagging strands, and which repairs/replicates mitochondrial DNA?

   Pol $\varepsilon$ (epsilon) extends the leading strand, Pol $\delta$ (delta) the lagging strand, and Pol $\gamma$ (gamma) replicates mitochondrial DNA.

7. What proofreading activity corrects mismatched nucleotides during replication, and in which direction does it act?

   The $3' \to 5'$ exonuclease activity of DNA polymerase removes mispaired bases immediately after insertion.

8. What is the role of telomerase, and why is it relevant to the end-replication problem?

   Telomerase is a reverse transcriptase with an RNA template that extends the $3'$ end of chromosomes with repeat sequences (TTAGGG in humans), preventing progressive shortening of lagging-strand ends.

9. Which DNA repair pathway is defective in xeroderma pigmentosum, and what lesion does it remove?

   Nucleotide excision repair (NER), which removes bulky/helix-distorting lesions such as pyrimidine (thymine) dimers caused by UV light.

10. What DNA repair defect underlies hereditary nonpolyposis colorectal cancer (Lynch syndrome)?

    Defective mismatch repair (MMR), causing microsatellite instability due to uncorrected replication errors.

11. Compare the substrate and product of transcription with those of replication.

    Transcription copies a DNA template into single-stranded RNA using ribonucleotides; replication copies DNA into DNA. RNA polymerase, unlike DNA polymerase, needs no primer and lacks proofreading.

12. Which eukaryotic RNA polymerase synthesizes mRNA, and what toxin inhibits it?

    RNA polymerase II synthesizes mRNA (and some snRNA). It is inhibited by $\alpha$-amanitin from Amanita phalloides.

13. What do eukaryotic RNA polymerases I, II, and III each transcribe?

    Pol I: rRNA (except 5S); Pol II: mRNA, snRNA, miRNA; Pol III: tRNA and 5S rRNA.

14. List the three major post-transcriptional modifications of eukaryotic pre-mRNA.

    (1) $5'$ 7-methylguanosine cap, (2) $3'$ poly-A tail, and (3) splicing to remove introns and join exons.

15. What is the consensus promoter element recognized by RNA polymerase II located ~25 bp upstream of the start site?

    The TATA box (Hogness box), bound by TBP within the general transcription factor TFIID.

16. What is the composition and function of the spliceosome?

    A complex of snRNPs (U1, U2, U4, U5, U6) plus proteins that removes introns from pre-mRNA; antibodies to snRNPs (anti-Smith) are specific for SLE.

17. Distinguish exons from introns.

    Exons are the EXpressed sequences retained in mature mRNA; introns are INtervening, non-coding sequences removed by splicing (INtron IN the trash).

18. What is the wobble hypothesis in translation?

    The $3'$ (first) base of a codon pairs stringently, but the $5'$ base of the anticodon (wobble position) can form nonstandard pairs, so one tRNA can read multiple codons.

19. Which codons are the start and stop codons in translation?

    Start: AUG (codes for methionine). Stop codons: UAA, UAG, UGA (mnemonic: U Are Away / U Go Away).

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