Which of the following is the primary biochemical function of vitamin B₁₂ (cobalamin)?

Explanation

## Vitamin B₁₂ (Cobalamin): Biochemical Functions **Key Point:** Vitamin B₁₂ is an essential cofactor for two critical enzymes: **methylmalonyl-CoA mutase** and **methionine synthase**. Deficiency of either function leads to characteristic metabolic and neurological sequelae. ### Enzyme 1: Methylmalonyl-CoA Mutase - **Reaction:** Methylmalonyl-CoA → Succinyl-CoA (final step of propionate metabolism) - **Location:** Mitochondrial matrix - **Consequence of deficiency:** Accumulation of methylmalonic acid (MMA) → elevated urinary MMA (diagnostic marker) - **Clinical effect:** Contributes to neurological damage and metabolic acidosis ### Enzyme 2: Methionine Synthase - **Reaction:** Homocysteine + 5-methyltetrahydrofolate → Methionine + tetrahydrofolate (THF) - **Location:** Cytoplasm - **Consequence of deficiency:** ↑ Homocysteine, ↓ Methionine, ↓ THF regeneration - **Clinical effects:** - Impaired DNA synthesis → megaloblastic anemia - Impaired myelin synthesis → subacute combined degeneration (SCD) of spinal cord - Neuropsychiatric manifestations (dementia, ataxia, paresthesias) ### The "Methylation Trap" Hypothesis B₁₂ deficiency prevents regeneration of THF from 5-methylTHF, trapping folate in its methylated form and impairing nucleotide synthesis — explaining the megaloblastic anemia. **High-Yield:** Elevated **methylmalonic acid (MMA)** and **homocysteine** are the biochemical hallmarks of B₁₂ deficiency and help distinguish it from folate deficiency (which ↑ homocysteine but NOT MMA). **Mnemonic:** **"MM-MS"** — **M**ethylmalonyl-CoA **M**utase and **M**ethionine **S**ynthase. | Feature | B₁₂ Deficiency | Folate Deficiency | |---------|---|---| | **Methylmalonic acid** | ↑↑ | Normal | | **Homocysteine** | ↑↑ | ↑↑ | | **Neurological signs** | Yes (SCD) | No | | **Megaloblastic anemia** | Yes | Yes | [cite:Robbins 10e Ch 14]