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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)

A hypoglycemic toddler who isn't spilling ketones

An 18-month-old is brought in lethargic and vomiting after two days of a viral illness with poor intake. Parents report she 'just went limp'. She is hypotonic with a mildly enlarged liver.

Fingerstick glucose32 mg/dL↓↓
Urine ketonestrace / negative↓ (inappropriate)
Ammoniamildly ↑
AST/ALT
Acylcarnitine profile↑ C8 octanoylcarnitine

MCAD deficiency (medium-chain acyl-CoA dehydrogenase)

Hypoglycemia WITHOUT ketones = the liver cannot oxidise fat. A fasting stress unmasked the most common fatty acid oxidation disorder.

Condition card: MCAD deficiency →Pathway map →

  1. Illness + poor intake → hepatic glycogen (proportionally small in a toddler) is exhausted within hours.

Pathways involved: Lipolysis, carnitine shuttle & β-oxidation, Ketogenesis & ketone body use, Gluconeogenesis. Drill them one at a time in Metabolic pathways.

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