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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)

Jaundice, vomiting and E. coli sepsis in a 5-day-old

A 5-day-old breastfed neonate has vomiting, poor feeding, jaundice and hepatomegaly. Blood cultures grow E. coli. The ophthalmologist notes early lens opacities.

Urine reducing substancespositive+
Urine glucose oxidasenegative
Bilirubin↑ (mixed)
AST/ALT
RBC GALT activityabsent↓↓
Galactose-1-phosphate (RBC)↑↑

Classic galactosemia (GALT deficiency)

Galactose-1-phosphate is the toxin; galactitol from aldose reductase adds the cataract; neutrophil dysfunction adds the E. coli.

Condition card: Galactosemia (GALT deficiency) →Pathway map →

  1. Lactose (milk) → lactase → glucose + galactose; galactokinase makes galactose-1-P normally.

Pathways involved: Galactose metabolism (Leloir pathway), NADPH — sources and what needs it. Drill them one at a time in Metabolic pathways.

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