Home › Certifications › USMLE Step 1 › General Principles of Foundational Science
27 multiple-choice questions and 54 flashcards on General Principles of Foundational Science, about 16% of the USMLE Step 1 bank. Every one carries a written rationale.
General Principles of Foundational Science is one of 10 chapters in CoStudy's USMLE Step 1 — Medical Licensing bank, and it holds 27 of the bank's 172 multiple-choice questions — roughly 16% of the total. That proportion is not arbitrary: chapters follow the certifying body's published exam outline, and the number of questions in each is set by that domain's published weight, so the share of your practice time this chapter takes matches the share of the real exam it accounts for.
Studying by chapter is worth doing once you have a diagnostic score. A single overall percentage tells you whether you are close; it does not tell you which domain is dragging. Working a weak chapter in isolation, and re-testing it in isolation, is the fastest way to move a score that has stalled — and it is why the mock exams in CoStudy report by domain rather than as one number.
10 questions drawn from this chapter, with the full rationale shown — the controlling principle behind the right answer, and why each wrong option tempts and fails.
Down syndrome (trisomy 21) features commonly include:
Answer: C — Distinctive facial features, hypotonia, intellectual disability, increased risk of congenital heart disease (e.g., AV septal defects), early-onset Alzheimer-like changes, and increased leukemia risk
C) Standard features. A/B/D) Each contradicts.
Which immunoglobulin isotype is the FIRST produced in a primary immune response?
Answer: D — IgM
IgM is the first antibody secreted by plasma cells in a primary response. Class switching to IgG, IgA, or IgE happens later under cytokine signaling. IgM is also the antibody used for blood-typing because it's a strong agglutinator (pentameric).
A 6-month-old infant develops hypoglycemia, hepatomegaly, and lactic acidosis after fasting. Liver biopsy shows accumulation of glycogen with normal structure. Glucagon does not raise blood glucose. Which enzyme is MOST likely deficient?
Answer: B — Glucose-6-phosphatase
B) Correct: Von Gierke disease (GSD type I) — glucose-6-phosphatase deficiency prevents release of free glucose from liver, causing severe fasting hypoglycemia, hepatomegaly, and lactic acidosis (excess pyruvate shunted to lactate). A) Muscle phosphorylase deficiency = McArdle (GSD V) — exercise intolerance, not infantile hypoglycemia. C) Acid maltase deficiency = Pompe (GSD II) — cardiomegaly and hypotonia (lysosomal). D) Debranching enzyme = Cori (GSD III) — milder, limit dextrin accumulates (abnormal structure, not normal). E) Branching enzyme = Andersen (GSD IV) — also has abnormal glycogen structure.
A 30-year-old man with no prior medical history has fever, headache, and a stiff neck. CSF: 1200 WBCs (90% neutrophils), glucose 25 (serum 100), protein 250. Gram stain shows gram-positive diplococci. Which is the MOST likely organism?
Answer: B — Streptococcus pneumoniae
B) Correct: S. pneumoniae is the most common cause of bacterial meningitis in adults (gram-positive lancet-shaped diplococci). A) N. meningitidis is gram-NEGATIVE diplococci (Gram stain trap), seen in adolescents/young adults with petechiae. C) Listeria is a gram-positive ROD, important in neonates, pregnant women, immunocompromised, and elderly. D) GBS is a gram-positive coccus but is a neonatal pathogen, not adult. E) H. influenzae is gram-negative coccobacilli; dramatic decline with Hib vaccine.
Which antibiotic class works by inhibiting the 50S ribosomal subunit?
Answer: C — Macrolides
Macrolides (azithromycin, erythromycin, clarithromycin) bind the 23S rRNA of the 50S subunit, blocking peptide translocation. Mnemonic for 50S inhibitors: 'Buy AT 30, CCEL at 50' — Chloramphenicol, Clindamycin, Erythromycin, Linezolid. Aminoglycosides (A) and tetracyclines (B) hit the 30S; fluoroquinolones (D) inhibit DNA gyrase.
Down syndrome (trisomy 21) is most commonly caused by:
Answer: C — Meiotic nondisjunction (typically maternal)
~95% of Down syndrome is from maternal meiotic nondisjunction (risk rises with maternal age). ~4% from Robertsonian translocation (often involving chr 14); ~1% mosaicism.
A 2-year-old child has developmental delay, fair skin, blond hair, blue eyes, and a musty body odor. Newborn screening was not performed. Which enzyme deficiency is MOST likely responsible?
Answer: C — Phenylalanine hydroxylase
C) Correct: phenylketonuria (PKU) — phenylalanine hydroxylase deficiency causes phenylalanine accumulation. Tyrosine becomes essential (hypopigmentation), and phenyl ketones in urine cause musty odor. A) Homogentisate oxidase deficiency = alkaptonuria (dark urine on standing, ochronosis). B) BCKAD deficiency = maple syrup urine disease (sweet odor, not musty) — off-by-one urine-odor trap. D) Tyrosinase deficiency = albinism (hypopigmentation only, no developmental delay or musty odor). E) Cystathionine β-synthase = homocystinuria (Marfanoid habitus, downward lens dislocation, thromboses).
Which enzyme is rate-limiting in cholesterol biosynthesis and the molecular target of statins?
Answer: B — HMG-CoA reductase
HMG-CoA reductase catalyzes the rate-limiting step (HMG-CoA → mevalonate) in cholesterol synthesis. Statins competitively inhibit this enzyme. (A) is for fatty-acid synthesis; (C) is TCA cycle; (D) is downstream in cholesterol synthesis but not rate-limiting.
A 25-year-old woman with epilepsy is planning pregnancy. Which antiepileptic has the GREATEST teratogenic risk and should be avoided?
Answer: C — Valproate
C) Correct: valproate is the MOST teratogenic AED — neural tube defects, craniofacial abnormalities, and decreased IQ in offspring. Avoid in women of childbearing age when possible. A) Levetiracetam has the lowest teratogenic risk and is preferred in pregnancy. B) Lamotrigine is also relatively safe in pregnancy. D) Gabapentin has limited but reassuring data. E) Carbamazepine causes neural tube defects but at lower rates than valproate — half-right trap; both are teratogenic, but valproate is worse.
A 5-year-old boy has progressive proximal muscle weakness, calf pseudohypertrophy, and a positive Gower sign. CK is markedly elevated. Which is the underlying defect?
Answer: A — Frameshift mutation in dystrophin gene with no functional protein
A) Correct: Duchenne muscular dystrophy is caused by frameshift/deletion mutations in dystrophin → NO functional protein. Severe early-onset weakness, wheelchair by ~12, death from cardiopulmonary failure. B) In-frame point mutations producing a truncated but PARTIALLY functional dystrophin = Becker MD (milder, later onset) — off-by-one mutation/disease trap. C) CTG expansion in DMPK = myotonic dystrophy (myotonia, frontal balding, cataracts). D) SMN1 mutation = spinal muscular atrophy (anterior horn cell). E) Anti-AChR = myasthenia gravis (no pseudohypertrophy).
4 cards from the 54 in this chapter.
Krebs cycle ATP yield (per cycle)?
1 ATP (GTP) + 3 NADH + 1 FADH2 per acetyl-CoA. Total ~10 ATP equivalents.
Vitamin K deficiency?
Coagulopathy. Increased PT/INR. Common in newborns.
Cystic fibrosis mutation?
ΔF508 in CFTR (chloride channel). Autosomal recessive. Lungs, pancreas, sweat glands.
Best Step 1 resources?
First Aid (gold standard), UWorld (must), Pathoma, SketchyMicro/Pharm.
These are a sample. The full General Principles of Foundational Science chapter runs 81 items with per-chapter progress tracking, on the web and in the iOS app.
Open USMLE Step 1 in CoStudy →