Biochemistry can feel overwhelming, but most exam questions come from a short list of core concepts. Learn these 10 topics and you will cover the majority of what USMLE Step 1 tests.

Top 10 High-Yield Biochemistry Concepts

  1. Glycolysis regulation — Three irreversible enzymes (hexokinase, PFK-1, pyruvate kinase) control the rate; PFK-1 is the key regulatory step and is activated by AMP and fructose-2,6-bisphosphate.
  2. TCA cycle (Krebs cycle) — Eight reactions in the mitochondrial matrix that produce NADH, FADH2, and GTP; isocitrate dehydrogenase is the main regulated step.
  3. Electron transport chain (ETC) and oxidative phosphorylation — Complexes I–IV pump protons across the inner mitochondrial membrane; Complex IV (cytochrome c oxidase) is inhibited by cyanide and carbon monoxide.
  4. Key enzyme deficiencies — G6PD deficiency causes hemolytic anemia triggered by oxidative stress (e.g., primaquine, fava beans); pyruvate kinase deficiency is the most common cause of hereditary hemolytic anemia without a specific trigger.
  5. Fat-soluble vitamin deficiencies — Vitamins A, D, E, and K are stored in fat and liver; each has distinct clinical presentations (night blindness, rickets/osteomalacia, hemolytic anemia in newborns, bleeding disorder).
  6. Water-soluble vitamin deficiencies — B1 (thiamine) deficiency causes Wernicke–Korsakoff and beriberi; B3 (niacin) causes pellagra; B12 deficiency causes megaloblastic anemia with neurological signs.
  7. Urea cycle — Converts toxic ammonia to urea for excretion; begins and ends in the mitochondria/cytosol; ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and is X-linked.
  8. Glycogen storage diseases — Caused by enzyme defects in glycogen synthesis or breakdown; Von Gierke (G6Pase, Type I) and Pompe (acid maltase/α-1,4-glucosidase, Type II) are the highest-yield.
  9. Lysosomal storage diseases — Enzyme deficiencies cause substrate buildup in lysosomes; Gaucher (glucocerebrosidase), Niemann–Pick (sphingomyelinase), Tay–Sachs (hexosaminidase A), and Fabry (α-galactosidase A) are the most tested.
  10. DNA replication and repair — Leading strand is synthesized continuously, lagging strand in Okazaki fragments; mismatch repair defects cause microsatellite instability (Lynch syndrome); nucleotide excision repair fixes bulky lesions (e.g., UV-induced thymine dimers).

Try 5 free questions to see how these topics appear in real exam-style questions.

Mnemonics to Remember Them

Fat-Soluble Vitamins — "ADEK"

The letters spell out the four fat-soluble vitamins in order:

  • A — Vitamin A (retinol)
  • D — Vitamin D (calciferol)
  • E — Vitamin E (tocopherol)
  • K — Vitamin K (phylloquinone)

Simple tip: fat-soluble vitamins can accumulate to toxic levels because the body stores them. Water-soluble vitamins (B group, C) are excreted in urine and rarely cause toxicity.

Glycolysis Irreversible Enzymes — "Pathway Kinases Feel Good"

The three irreversible steps of glycolysis are catalysed by:

  • PhosPhofructokinase-1 (PFK-1) — step 3, the main control point
  • Kinase (hexoKinase / glucokinase) — step 1
  • Pyruvate Kinase — step 10 (last step)

Remember: these three enzymes are bypassed during gluconeogenesis using different enzymes.

Lysosomal Storage Diseases — "Gaucher Gets Neuronal Picks, Takes Fats Away"

A rough story to link each disease to its missing enzyme and substrate:

  • Gaucher → Glucocerebrosidase → glucocerebroside builds up → bone marrow macrophages (Gaucher cells)
  • Niemann–Pick → sPhingomyelinase → sphingomyelin builds up → "sea-blue" histiocytes, cherry-red spot
  • Tay–Sachs → hexosaminidase A → GM2 ganglioside builds up → cherry-red spot, no organomegaly
  • Fabry → α-galactosidase A → ceramide trihexoside builds up → X-linked, angiokeratomas, renal failure

Play a quick game to drill these enzyme–disease pairs in under three minutes.

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How to Use These in Your Study Sessions

  • Active recall beats passive reading. Close this page and write down all 10 concepts from memory. Check what you missed.
  • Link the mnemonic to the clinical vignette. Exams describe a patient, not a pathway. Practise connecting the biochemistry to signs and symptoms.
  • Repeat at intervals. Review once today, once in 2 days, once in a week. Spaced repetition locks concepts into long-term memory.
  • Test yourself with questions. Reading and re-reading is not enough. Active testing reveals gaps that reading hides.

Biochemistry questions reward students who understand why pathways are regulated, not just which enzymes exist. Focus on regulation, clinical presentations of deficiencies, and the key disease associations for each pathway.