Learn / Metabolism
Metabolic pathways
Every FMK pathway as a clickable map. Pick one pathway to hammer it — next step, enzyme, regulator, cofactor, and the facts that get tested (NADPH and who needs it, rate-limiting steps, deficiencies) — or set it to all pathways for a mixed drill. Every answer says which enzyme and which pathway.
Sphingolipid degradation & the sphingolipidoses
Ceramide (sphingosine + fatty acid)
Made from Galactocerebroside (Gal + ceramide) by Galactocerebrosidase (GALC)
Galactocerebrosidase (GALC) · irreversible — Sphingolipid degradation & the sphingolipidoses
Deficiency: Krabbe disease (AR, GALC) — galactocerebroside and the toxic metabolite psychosine accumulate: severe myelin loss, developmental regression, optic atrophy, peripheral neuropathy, GLOBOID cells
Also called galactosylceramidase. Its substrate is the main glycolipid of myelin, so the disease is a leukodystrophy.
Condition cards:Krabbe disease →
Made from Glucocerebroside (Glc + ceramide) by Glucocerebrosidase (β-glucosidase)
Glucocerebrosidase (β-glucosidase) · irreversible — Sphingolipid degradation & the sphingolipidoses
Deficiency: Gaucher disease (AR, GBA) — glucocerebroside accumulates in macrophages: HEPATOSPLENOMEGALY, bone crises and erosion (Erlenmeyer-flask femur), pancytopenia, 'crumpled tissue paper' macrophages
The commonest lysosomal storage disease. Treatable — recombinant enzyme replacement works well for the non-neuronopathic type 1.
Condition cards:Gaucher disease →
Made from Sphingomyelin (ceramide + phosphocholine) by Sphingomyelinase (acid sphingomyelinase)
Sphingomyelinase (acid sphingomyelinase) · irreversible — Sphingolipid degradation & the sphingolipidoses
Deficiency: Niemann-Pick disease (AR, SMPD1) — sphingomyelin accumulates in monocytes/macrophages: hepatosplenomegaly, foam cells, cherry-red macula WITH organomegaly. Type A ~1% activity, rapid neurodegeneration fatal in early childhood; type B ~10%, longer survival with minimal neural involvement
"Sphingomyelinase cleaves sphingomyelin → ceramide + phosphorylcholine" (s16). Sphingomyelin is a major component of the myelin sheath, and the lecithin/sphingomyelin ratio > 2 at ~35 weeks is the fetal lung maturity test (s10, s15).
Condition cards:Niemann-Pick disease →
Becomes Sphingosine via Ceramidase
Ceramidase · irreversible — Sphingolipid degradation & the sphingolipidoses
Cofactors: H₂O
Deficiency: Farber disease (AR, ASAH1) — ceramide accumulates: hoarse cry from laryngeal nodules, painful swollen joints with deformity, subcutaneous nodules over the joints and spine
The last hydrolysis: ceramide is split back into its two parts.
Condition cards:Farber disease →
Becomes Fatty acid via Ceramidase
Ceramidase · irreversible — Sphingolipid degradation & the sphingolipidoses
Cofactors: H₂O
The fatty acid released can be re-used or oxidised.
Condition cards:Farber disease →