## Vitamin B12 (Cobalamin) — Biochemical Role **Key Point:** Vitamin B12 functions as a coenzyme in two critical enzymatic reactions: 1. **Methylmalonyl-CoA mutase** — converts methylmalonyl-CoA to succinyl-CoA (propionate metabolism) 2. **Methionine synthase** — converts homocysteine to methionine (one-carbon metabolism and DNA synthesis) ### Clinical Significance Deficiency of B12 leads to: - Accumulation of methylmalonic acid and homocysteine (elevated in serum and urine) - Impaired DNA synthesis → megaloblastic anemia - Neurological damage (subacute combined degeneration) due to myelin synthesis impairment ### Biochemical Consequences of Deficiency | Finding | Mechanism | |---------|----------| | Megaloblastic anemia | Impaired thymidylate synthesis (via methionine synthase) | | Elevated methylmalonic acid | Methylmalonyl-CoA mutase deficiency | | Elevated homocysteine | Methionine synthase deficiency | | Neurological symptoms | Impaired myelin synthesis and neuronal energy metabolism | **High-Yield:** The combination of **elevated methylmalonic acid + elevated homocysteine** is pathognomonic for B12 deficiency and distinguishes it from folate deficiency (which raises homocysteine only). **Mnemonic:** **"B12 Makes Methionine & Methylmalonate"** — remember the two key enzymes and their substrates.
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