United States Medical Licensing Examination (USMLE) Foundational Biomedical Sciences (Step 1 Core) Syllabus

Foundational Biomedical Sciences (Step 1 Core) syllabus — full chapter and topic list

Expand any chapter to see its topics and sub-topics. This is the whole examinable outline for Foundational Biomedical Sciences (Step 1 Core) in United States Medical Licensing Examination (USMLE), not a summary of it.

1. 1

   General Principles of Cell and Molecular Biology

   5 topics

   • Cell membrane and transport
     • Lipid bilayer structure and fluidity
     • Passive, facilitated, and active transport
     • Ion channels and electrochemical gradients
   • DNA replication, repair, and transcription
     • Replication fork enzymes and fidelity
     • DNA repair pathways and clinical defects
     • RNA polymerases and post-transcriptional modification
   • Translation and protein processing
     • Ribosome assembly and the genetic code
     • Post-translational modification and trafficking
   • Cell cycle and signal transduction
     • Cyclins, CDKs, and checkpoints
     • Second messenger and G-protein cascades
   • Apoptosis and cellular adaptation
     • Intrinsic and extrinsic apoptotic pathways
     • Hypertrophy, hyperplasia, atrophy, metaplasia
2. 2

   Biochemistry and Metabolism

   5 topics

   • Carbohydrate metabolism
     • Glycolysis and gluconeogenesis
     • Glycogen storage and disorders
     • Pentose phosphate pathway
   • Oxidative phosphorylation and the TCA cycle
     • Electron transport chain complexes
     • Uncouplers and inhibitors
   • Lipid and fatty acid metabolism
     • Beta-oxidation and ketogenesis
     • Cholesterol synthesis and lipoproteins
   • Amino acid and nitrogen metabolism
     • Urea cycle and hyperammonemia
     • Aminoacidopathies (PKU, MSUD, homocystinuria)
   • Vitamins, cofactors, and inborn errors
     • Water-soluble vitamin deficiencies
     • Fat-soluble vitamins and toxicity
3. 3

   Medical Genetics

   5 topics

   • Single-gene inheritance patterns
     • Autosomal dominant and recessive
     • X-linked and mitochondrial inheritance
   • Population genetics
     • Hardy-Weinberg equilibrium
     • Carrier frequency calculations
   • Chromosomal abnormalities
     • Trisomies and monosomies
     • Microdeletion and imprinting disorders
   • Modes of nontraditional inheritance
     • Anticipation and trinucleotide repeats
     • Genomic imprinting and uniparental disomy
   • Molecular diagnostics and gene therapy
4. 4

   Microbiology and Immunology Foundations

   6 topics

   • Bacteriology
     • Gram-positive and gram-negative classification
     • Virulence factors and toxins
   • Virology
     • DNA and RNA virus families
     • Viral replication strategies
   • Mycology and parasitology
   • Innate immunity
     • Complement system
     • Phagocytes and pattern recognition
   • Adaptive immunity
     • T-cell and B-cell development
     • MHC and antigen presentation
   • Hypersensitivity and immunodeficiency
     • Type I-IV reactions
     • Primary immunodeficiencies
5. 5

   General Pathology

   5 topics

   • Cellular injury and death
     • Reversible vs irreversible injury
     • Necrosis subtypes
   • Acute and chronic inflammation
     • Vascular and cellular events
     • Granulomatous inflammation
   • Tissue repair and wound healing
   • Hemodynamic disorders
     • Edema, thrombosis, embolism
     • Shock and infarction
   • Neoplasia
     • Oncogenes and tumor suppressors
     • Grading, staging, and tumor markers
6. 6

   General Pharmacology Principles

   5 topics

   • Pharmacokinetics
     • Absorption, distribution, metabolism, excretion
     • Clearance, half-life, and dosing
   • Pharmacodynamics
     • Dose-response and efficacy vs potency
     • Agonists, antagonists, and receptor theory
   • Drug metabolism and interactions
     • Cytochrome P450 inducers and inhibitors
   • Autonomic pharmacology
     • Cholinergic and adrenergic agents
   • Toxicology and antidotes

Foundational Biomedical Sciences (Step 1 Core) flashcards for United States Medical Licensing Examination (USMLE)

24 of 76 cards from the Foundational Biomedical Sciences (Step 1 Core) deck — real questions with worked answers.

1. What type of transport moves Na+ out and K+ into the cell against their gradients, and what is its stoichiometry and energy source?

   The Na+/K+-ATPase (primary active transport): pumps 3 Na+ out and 2 K+ in per ATP hydrolyzed, creating the electrochemical gradient.

2. Contrast facilitated diffusion with secondary active transport across the cell membrane.

   Facilitated diffusion moves solutes down their gradient via carriers/channels with no ATP. Secondary active transport moves a solute against its gradient using the energy stored in another ion's gradient (e.g., Na+-glucose symport).

3. In which direction does DNA polymerase synthesize, and which strand is made discontinuously?

   DNA polymerase synthesizes 5' to 3' (reading template 3' to 5'). The lagging strand is made discontinuously as Okazaki fragments; the leading strand is continuous.

4. Match the DNA repair defect to its disease: nucleotide excision repair, mismatch repair, and nonhomologous end joining.

   Nucleotide excision repair defect = xeroderma pigmentosum; mismatch repair defect = Lynch/HNPCC; nonhomologous end joining defect = ataxia-telangiectasia (and related).

5. Which RNA polymerase makes mRNA in eukaryotes, and what toxin inhibits it?

   RNA polymerase II makes mRNA (and snRNA); it is inhibited by alpha-amanitin (from Amanita phalloides).

6. What are the three major post-transcriptional modifications of eukaryotic mRNA?

   5' 7-methylguanosine cap, 3' poly-A tail, and splicing out of introns (joining exons).

7. During translation, which site of the ribosome holds the growing peptide chain and which accepts the incoming aminoacyl-tRNA?

   The P site holds the peptidyl-tRNA (growing chain); the A site accepts the incoming aminoacyl-tRNA; the E site is for exit of deacylated tRNA.

8. Where are proteins destined for secretion versus the cytosol synthesized?

   Secretory, membrane, and lysosomal proteins are made on ribosomes of the rough ER (signal sequence directs them there); cytosolic and peroxisomal proteins are made on free ribosomes.

9. Which cyclin-CDK complex drives the G1 to S transition, and what is the key tumor-suppressor checkpoint?

   Cyclin D-CDK4/6 (and cyclin E-CDK2) drives G1 to S; the Rb protein (released by phosphorylation, freeing E2F) and p53 govern the G1/S checkpoint.

10. Compare the second messengers generated by Gs, Gi, and Gq protein-coupled receptors.

    Gs increases cAMP (activates adenylyl cyclase); Gi decreases cAMP (inhibits adenylyl cyclase); Gq activates phospholipase C generating IP3 (releases Ca2+) and DAG (activates PKC).

11. Distinguish the morphologic and mechanistic features of apoptosis versus necrosis.

    Apoptosis: programmed, ATP-dependent, cell shrinkage, chromatin condensation, membrane intact, no inflammation. Necrosis: pathologic, cell swelling, membrane rupture, enzyme release, surrounding inflammation.

12. Name the intrinsic and extrinsic apoptotic pathways and a key regulator of each.

    Intrinsic (mitochondrial): triggered by cell injury/loss of survival signals, regulated by Bcl-2 (anti-apoptotic) vs Bax/Bak (pro-apoptotic), releases cytochrome c. Extrinsic: triggered by death receptors (Fas-FasL, TNF), activates caspase-8. Both converge on caspase-3.

13. Define and give an example of each: hypertrophy, hyperplasia, atrophy, metaplasia.

    Hypertrophy = larger cells (cardiac muscle in hypertension); hyperplasia = more cells (endometrium with estrogen); atrophy = decreased size/number (disuse muscle); metaplasia = one adult cell type replaced by another (Barrett esophagus, squamous to columnar).

14. What are the three irreversible (regulated) enzymes of glycolysis?

    Hexokinase/glucokinase, phosphofructokinase-1 (PFK-1, the rate-limiting step), and pyruvate kinase.

15. What is the rate-limiting enzyme of gluconeogenesis and where does the pathway predominantly occur?

    Fructose-1,6-bisphosphatase is rate-limiting; gluconeogenesis occurs mainly in the liver (and kidney). Key enzymes: pyruvate carboxylase, PEPCK, fructose-1,6-bisphosphatase, glucose-6-phosphatase.

16. What is the main purpose and rate-limiting enzyme of the HMP/pentose phosphate pathway?

    It produces NADPH (for reductive biosynthesis and glutathione) and ribose-5-phosphate (for nucleotides); rate-limiting enzyme is glucose-6-phosphate dehydrogenase (G6PD).

17. Which electron transport chain complex is the site of ATP synthesis, and what does cyanide inhibit?

    Complex V (ATP synthase) makes ATP. Cyanide and CO inhibit Complex IV (cytochrome c oxidase); rotenone inhibits Complex I; antimycin A inhibits Complex III; oligomycin inhibits ATP synthase.

18. What is the rate-limiting enzyme of the TCA cycle and the net high-energy yield per acetyl-CoA?

    Isocitrate dehydrogenase is rate-limiting. Per acetyl-CoA: 3 NADH, 1 FADH2, 1 GTP, and 2 CO2 released.

19. How do uncoupling agents (e.g., 2,4-dinitrophenol) affect oxidative phosphorylation?

    They dissipate the proton gradient across the inner mitochondrial membrane, so electron transport continues but ATP synthesis decreases; energy is released as heat (also brown fat thermogenin/UCP1).

20. What is the rate-limiting and committed step of fatty acid synthesis, and what cofactor does the enzyme use?

    Acetyl-CoA carboxylase converting acetyl-CoA to malonyl-CoA; it requires biotin and is activated by citrate/insulin, inhibited by glucagon and palmitoyl-CoA.

21. What molecule shuttles fatty acids into the mitochondria for beta-oxidation, and what inhibits this shuttle?

    Carnitine (via carnitine acyltransferase I/CPT-1). Malonyl-CoA inhibits CPT-1, preventing simultaneous fatty acid synthesis and oxidation.

22. Name the three ketone bodies and the conditions that promote ketogenesis.

    Acetoacetate, beta-hydroxybutyrate, and acetone. Ketogenesis (in liver) increases in prolonged fasting/starvation, diabetic ketoacidosis, and alcoholism due to high acetyl-CoA and low oxaloacetate.

23. What is the rate-limiting enzyme of cholesterol synthesis and the drug class that inhibits it?

    HMG-CoA reductase; inhibited by statins (HMG-CoA reductase inhibitors).

24. What are the two main mechanisms for disposing of ammonia, and where does the urea cycle's rate-limiting step occur?

    Glutamine (via glutamine synthetase) transports ammonia, and the urea cycle in the liver excretes it. The rate-limiting enzyme is carbamoyl phosphate synthetase I (mitochondria), requiring N-acetylglutamate as activator.

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