CoFactor: Adenosylcobalamin

General information

2D representation

Key facts

Tags

• phosphate-containing cofactors
• nucleotide-containing cofactors
• porphyrin-like cofactors

Molecular function

The cofactor assists the catalysis of molecular rearrangements, methylations and dehalogenations [2].

Chemical properties

The cobalt atom is coordinated by 4 nitrogen atoms from the corrin ring. The axial ligands are the endogenous ligand, 5,6-dimethylbenzimidazole (green) and an adenosyl portion (blue).

The molecule is highly methylated. This encourages the molecule to adopt the appropriate conjugation state and prevents prototrophic rearrangement and oxidation [1].

The corrin ring is one C-atom shorter than in the other corrin cofactors (hemes, F430...). The shortening allows for a tighter coordination of the cobalt atom [1].

Pathways

B12-dependent enzymes occur predominantly in anaerobic organisms (B12 is sensitive to oxygen), but an exception is the methylmalonyl-CoA mutase, which is involved in propionate formation (in propionibacteria) and in proprionate oxidation (in syntrophic bacteria and animals) [4]. In anaerobic organisms, eliminases (they have SAM counterparts) and mutases can be B12-dependant [4].

In the enzymes glycerol dehydratase and lysine-5,6-aminomutase, B12 becomes inactivated during the turnover and is recycled by a chaperone-like reactivation factor (ATP-dependent) [4].

B12-dependant enzymes can be classified into three classes of enzymes: isomerases(A), methyltransferases(B) and reductive dehalogenases(B) [3]. Group A (isomerases) mainly catalyses 1,2-rearrangements, often in anaerobic fermentative processes [3].

1. Radical generation by homolysis of the weak Co-C sigma bond [4]
2. Radical reacts with substrate to form substrate-like radical [4]
3. Conversion to product-like radical [4]
4. Conversion to product and usually recycling of radical [4]

Isomerases (A) are mainly involved in anaerobic fermentative processes [3].

Comment

It is not clear how old B12 is in evolutionary terms. On the one hand, it has a nucleotide loop which could be a hint that it was involved in ribozymes in a potential RNA world. Further more it is involved in nucleotide reduction, a very basic process in nature [1]. On the other hand, the enzyme ribonucleotide reductase exists in 3 different variations, one B12-dependant, the other two using SAM and molecular oxygen. The SAM-dependant one seems to be the oldest [1]

Some bacteria in the lower intestine produce a form of B12 that cannot be taken up by the human metabolism, hence most B12 has to come from the diet[3]. Meat, diary products and eggs are good sources of B12[3].

B12 is only synthesised in prokaryotic organisms [3]. Higher plants don’t require it, because they have an alternative from of methionine synthase called MetE. For humans, animal products are the best source for B12. Vegetarians can retrieve it e.g. from algae in sushi [3].

Cobalt is a trace element that is needed in very small quantities, mainly for the biosynthesis of Vitamin B12 (or its uptake) [2].

B12 deficiency results inpernicious anemia. In humans it affects the two enzymes that depend on it: methionine synthase and methylmalonyl-CoA mutase.

References

[1]	pubmed:17898893
[2]	pubmed:17898892
[3]	pubmed:17898891
[4]	pubmed:16704345