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)

Lifelong anemia with burr cells

A 16-year-old with chronic mild jaundice and splenomegaly has had transfusions twice in childhood. Smear shows echinocytes (burr cells). Her parents are both healthy.

Hemoglobin8.5 g/dL↓
Reticulocytes↑↑
Indirect bilirubin↑↑
RBC 2,3-BPG↑↑
RBC ATP↓↓
Osmotic fragilitynormal

Pyruvate kinase deficiency

Red cells have no mitochondria; block the last ATP-making step of glycolysis and they can't keep their membrane pumps running.

Condition card: Pyruvate kinase (PK) deficiency →Pathway map →

  1. RBCs lack mitochondria — glycolysis is their ONLY ATP source (2 ATP per glucose).
  2. …
  3. …
  4. …
  5. …
  6. …

Pathways involved: Glycolysis. Drill them one at a time in Metabolic pathways.

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