Learning Objectives

• Identify the two essential enzymes requiring Vitamin B12 as a cofactor.
• Explain the complex absorption pathway involving Intrinsic Factor and the terminal ileum.
• Differentiate B12 deficiency from B9 deficiency using neurological findings and Methylmalonic Acid (MMA) levels.
• Identify various etiologies of malabsorption, from Pernicious Anemia to dietary choices.

1. Biochemical Function

Vitamin B12 (Cobalamin) contains a cobalt atom and is essential for DNA synthesis and myelin maintenance. It serves as a cofactor for two critical reactions:

• Methionine Synthase: Transfers methyl groups to homocysteine to form Methionine. This reaction also regenerates THF from methyl-THF (linking B12 to the folate cycle).
• Methylmalonyl-CoA Mutase: Converts Methylmalonyl-CoA to Succinyl-CoA. This is vital for odd-chain fatty acid metabolism.

2. Absorption and Storage

B12 absorption is a “multi-step journey” requiring gastric, pancreatic, and ileal cooperation. Unlike other water-soluble vitamins, the liver maintains a large reserve pool that lasts 3–4 years.

• Source: Found exclusively in animal products.
• Intrinsic Factor (IF): Secreted by gastric parietal cells; binds B12 in the duodenum.
• Terminal Ileum: The specific site where the IF-B12 complex is absorbed.

3. Deficiency: Hematologic & Neurologic Findings

A hallmark of B12 deficiency is that folate (B9) supplementation can mask the anemia, but the irreversible neurological damage will continue to progress.

4. Common Etiologies

• Pernicious Anemia: Autoimmune destruction of parietal cells (loss of IF).
• Gastric Bypass: Loss of stomach surface area for IF production.
• Crohn’s Disease / Resection: Damage to or absence of the terminal ileum.
• Diphyllobothrium latum: Fish tapeworm that competes for B12 in the gut.
• Veganism: Strict avoidance of animal products.

Activity

Activity