Eric Holland OMS-I · ex-software engineer

Learn / Metabolism / The test

Metabolic reasoning

Whole-map thinking. Each case is a chain of cause → effect that ends in the labs: why DKA has ketones and hyperglycemia, why a drinker goes hypoglycemic, why an infant with MCAD deficiency spills no ketones. Walk through the chain on the map, then order it yourself, answer the why questions, or diagnose from the labs.

Case
The big map. Highlighted boxes are the parts of metabolism the current step is about. Scroll sideways when zoomed.
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GlycogenGlycogenGlucoseGlucoseGalactoseGalactoseFructoseFructoseGlucose-6-phosphateGlucose-6-phosphateRibose-5-P + NADPHRibose-5-P + NADPHFructose-6-phosphateFructose-6-phosphateFructose-1,6-bisPFructose-1,6-bisPG3P / DHAPG3P / DHAPGlycerol (fat)Glycerol (fat)PhosphoenolpyruvatePhosphoenolpyruvatePyruvatePyruvateLactateLactateAlanine (amino acids)Alanine (amino acids)Acetyl-CoAAcetyl-CoAOxaloacetateOxaloacetateCitrateCitrateTCA cycle → NADH/FADH₂TCA cycle → NADH/FADH₂ETC → ATPETC → ATPFatty acidsFatty acidsTriacylglycerolTriacylglycerolKetone bodiesKetone bodiesCholesterolCholesterolEthanolEthanolGlycogenolysis (phosphorylase)Hexokinase / glucokinaseLeloir pathway (GALT)HMP shunt (G6PD)GlycolysisPFK-1 ★ / FBPase-1AldolaseFructokinase → aldolase B(bypasses PFK-1)Glycerol kinase (liver)Hormone-sensitive lipaseLower glycolysis (2 ATP, 2 NADH)Pyruvate kinaseALT (glucose-alanine cycle)LDH (anaerobic)PDH (irreversible; thiamine)ADH → ALDH (2 NADH)Pyruvate carboxylase (biotin; +acetyl-CoA)Citrate synthaseCitrate synthaseTCA cycleOXPHOSATP-citrate lyase → ACC → FAS(needs NADPH)Hormone-sensitive lipaseHMG-CoA synthase / lyase (liver)HMG-CoA reductase (cytosol)

Dark urine three days after an antimalarial

A 24-year-old man of Mediterranean descent develops fatigue, jaundice and dark urine three days after starting primaquine before travel. He also ate a fava-bean dish at a family dinner.

Hemoglobin8.1 g/dL↓
Reticulocytes↑↑
Indirect bilirubin↑↑
LDH↑↑
Haptoglobin↓↓
SmearHeinz bodies, bite cells

G6PD deficiency with oxidant-induced hemolysis

Red cells have only one source of NADPH; without it, glutathione can't be regenerated and hemoglobin oxidises.

Condition card: G6PD deficiency (incl. favism) →Pathway map →

  1. G6PD (X-linked) is the rate-limiting enzyme of the HMP shunt — the RBC's only NADPH source (no malic enzyme, no mitochondria).
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Pathways involved: HMP shunt (pentose phosphate pathway), NADPH — sources and what needs it. Drill them one at a time in Metabolic pathways.

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