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)

Confused and sweaty after a binge

A 34-year-old man with alcohol use disorder is brought to the ED after a drinking binge. He has not eaten in 24 hours. He is confused and diaphoretic, tachycardic.

Glucose38 mg/dL↓↓
Blood alcoholelevated↑
Lactate↑↑
Anion gap↑↑
Ketonesmild ↑↑

Alcoholic (fasting) hypoglycemia

Two NADH per ethanol steal the substrates gluconeogenesis needs, in a man whose glycogen ran out hours ago.

Condition card: Alcohol-induced (alcoholic) hypoglycemia →Pathway map →

  1. 24 hours fasted → hepatic glycogen is gone → blood glucose now depends entirely on gluconeogenesis.
  2. …
  3. …
  4. …
  5. …
  6. …
  7. …

Pathways involved: Ethanol metabolism, Gluconeogenesis. Drill them one at a time in Metabolic pathways.

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