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.
Zoom
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)

Lactic acidosis in an infant that improves on a fat diet

A 4-month-old boy has severe developmental delay, hypotonia, seizures and a persistent lactic acidosis that worsens with carbohydrate feeds and improves on a high-fat diet.

Lactate↑↑
Pyruvate↑↑
Lactate:pyruvate rationormal (<20)
Alanine
Glucosenormal

Pyruvate dehydrogenase complex deficiency (E1α, X-linked)

Pyruvate has three exits — acetyl-CoA, lactate, alanine. Close the first and the other two overflow; feed fat to bypass it.

Condition card: Pyruvate dehydrogenase complex (PDHC) deficiency →Pathway map →

  1. Glucose → glycolysis → pyruvate normally; PDH E1α (needs TPP) is deficient → pyruvate can't become acetyl-CoA.

Pathways involved: PDH & TCA cycle, Glycolysis, Ketogenesis & ketone body use. Drill them one at a time in Metabolic pathways.

Something went wrong. Reload 🗙