Cobamide

Cobamide is a family of cobalt-containing corrinoid compounds that function as cofactors in a variety of biological reactions. The best known member is cobalamin, or vitamin B12, but the cobamide family includes many related compounds that differ in their upper and lower axial ligands.

Chemically, cobamides share a corrin ring with a central cobalt ion. The cobalt binds an upper axial ligand, which can be methyl, adenosyl, cyanide, hydroxyl, or other groups, and a lower axial ligand, typically 5,6-dimethylbenzimidazole linked through a nucleotide loop. Some cobamides have different lower ligands, such as pseudocobalamin, which uses adenine instead of DMB as the lower ligand. The coenzyme forms, such as adenosylcobalamin (coenzyme B12) and methylcobamide, participate directly in enzymatic catalysis.

Cobamides are produced de novo by certain bacteria and archaea; plants and animals do not synthesize them. They are acquired from diet or produced by microbial communities. Biosynthesis is complex and involves insertion of cobalt into the reduced corrin ring, assembly of the nucleotide loop, and attachment of the upper and lower ligands. There are aerobic and anaerobic pathways for cobamide biosynthesis, and the diversity of lower ligands contributes to a variety of natural cobamides.

Biological roles of cobamides include functions as cofactors for enzymes such as methionine synthase (methylcobamide) and methylmalonyl-CoA mutase (adenosylcobalamin). Not all organisms require B12, and many can use B12-independent enzymes or scavenge cobamides from their environment.

In humans, vitamin B12 is an essential cobamide for DNA synthesis and energy metabolism. Deficiency can cause megaloblastic anemia and neurologic symptoms, often due to inadequate intake, absorption problems, or metabolic defects. Treatment involves B12 supplementation.