Vitamin B12 functions as a coenzyme in two forms, adenosylcobalamin and methylcobalamin. Adenosylcobalamin is used by the enzyme methylmalonyl-CoA mutase to convert methylmalonyl-CoA to succinyl-CoA during fatty acid breakdown. Methylcobalamin is used by the enzyme methionine synthase to convert homocysteine to methionine, which provides methyl groups for many biological processes. Vitamin B12 deficiency can cause neurological abnormalities due to the accumulation of abnormal fatty acids and reductions in methionine and S-adenosylmethionine. Cyanocobalamin can also detox

1. Metabolic functions of
cyanocobalamin
Domina Petric, MD

2. April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
2
Coenzyme functions

3. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
3

4. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
4

5. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
5

6. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6

7. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7

8. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8

9. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9

10. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10

11. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
11

12. Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
April 23, 2018 12