Metabolic functions of cyanocobalamin Domina Petric, MD

Coenzyme functions December 5, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Coenzyme functions Vitamin B12 functions in metabolism in two coenzyme forms: adenosylcobalamin and methylcobalamin. The reaction catalyzed by the adenosylcobalamin-dependent enzyme involves the splitting of a carbon-carbon bond of the coenzyme with the formation of a free radical on the coenzyme, which can be transferred through an amino acid residue on the enzyme to the substrate. The reaction catalyzed by the methylcobalamin-dependent enzyme is a simple transfer of the single carbon moiety. December 5, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Methylmalonyl-CoA mutase The adenosylcobalamin-dependent enzyme methylmalonyl-CoA mutase catalyzes the conversion of methylmalonyl-CoA to succinyl-CoA in the degradation of propionate formed from odd-chain fatty acids. December 5, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Methylmalonyl-CoA mutase Methylmalonyl-CoA mutase is the first vitamin B12-dependent enzyme to be affected by deprivation of the vitamin. Owing to loss of methylmalonyl-CoA mutase activity, vitamin B12-deficient subjects show methylmalonic aciduria, especially after eating odd-chain fatty acids. December 5, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Methylmalonyl-CoA mutase The accumulation of methylmalonic acid can disrupt normal glucose and glutamic acid metabolism, apparently by inhibiting the tricarboxylic acid (TCA) cycle. Vitamin B12 deficiency can also cause a reversal of propionyl-CoA carboxylase activity, leading to the incorporation of the three-carbon propionyl-CoA in place of the two-carbon acetyl-CoA and resulting in the production of small amounts of odd-chain fatty acids. December 5, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Methylmalonyl-CoA mutase Increased methylmalonyl-CoA levels can also lead to its incorporation in place of malonyl-CoA, resulting in the synthesis of small amounts of methyl-branched chain fatty acids. It has been suggested that the neurological signs of vitamin B12 deficiency may result, at least in part, from the production of these abnormal fatty acids in neural tissues. December 5, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Methionine synthase Methionine synthase catalyzes the methylation of homocysteine to regenerate methionine, serving as the methyl group carrier (via methylcobalamin) between the donor 5-methyltetrahydrofolate (5′-methyl-FH4) and the acceptor homocysteine. December 5, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Methionine synthase Because of lost methionine synthase activity, vitamin B12-deficient subjects show reduced availability of methionine, the primary donor of methyl groups after its activation to S-adenosylmethionine (SAM). Losses of SAM lead to impairments in the synthesis of creatine, phospholipids and the neurotransmitter acetylcholine, all of which have broad impacts on physiological function. December 5, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Methionine synthase Low vitamin B12 status results in the accumulation of both homocysteine and 5′-methyl-FH4 (via the methylfolate trap). 5´-methyl-FH4 results in the loss of FH4, the key functional form of folate. Methionine synthase can also catalyze the reduction of nitrous oxide to elemental nitrogen: it generates a free radical that inactivates the enzyme. December 5, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Cyanide metabolism Cobalamins can bind cyanide to produce the nontoxic cyanocobalamin. Hydroxocobalamin is a well-recognized cyanide antidote. It has been proposed that vitamin B12 may have a role in the inactivation of the low levels of cyanide consumed in may fruits, beans and nuts. December 5, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. December 5, 2018