There are several related chemical structures consisting of a corrin nucleus surrounding a cobalt atom which show vitamin B12 activity. Collectively they can be described as the cobalamins.Theyare not found inplants and the sole natural source are microorganisms. The active compounds in mammals are hydroxycobalamin, methylcobalamin and adenosylcobalamin. Most of the normal human intake is derived from animal sources and strict vegans need to be supplemented with cyanocobalamin.
The absorption of the colabamins from the terminal ileum requires binding to a salivary haptocarrin and subsequently to a glycoprotein of molecular weight about 50000 secreted by gastric parietal cells (the so-called intrinsic factor). Deficiency states in the human are more commonly due to poor absorption as a result of an absence of the gastric intrinsic faetor than. to dietary inadequacy.
the conversion of eyanocobitlamin to its coenzyme form is catalysed by an enzyme system, cyanocobalamin coenzyme synthetase. The process involves a reaction with a deoxyadtmoiiyl moiety dericed from ATP and also requires diol or dithiol, a reduced flavin or reduced ferredoxin as the biological alkylating agent.
Utilising adenosyl cobalamin coenzymes
Vitamin B12 provides the prosthetic group for two classes of enzymes. The first (utilising adenosyl cobalamin coenzymes) is involved in various intramolecular group transfers (isomerisations) such as the breakdown of valine via methylmalonyl CoA and succinyl CoA. The second (using methylcobalamin) consists of methyltransferase reactions involved in the recycling of folate coenzymes (see below) and in the synthesis ofmethionine from homocysteine.
Human deficiency leads to a megaloblastic anaemia (large irregular red blood cells) and irreversible neurone damage (subacute combined degeneration of the cord). The red cell abnormality is probably caused ~y an inability to produce sufficient S-adenosylmethionine in the marrow for methyl group transfer in the formation of neucleotides for DNA synthesis. The neuropathy is probably due to a lack of methionine for methyl transfer to form the choline for the phospholipids and sphingomyelin which are required for the formation of myelin.
Vitamin B12 tonic
Because lassitude is a feature of the anaemia and the administration of vitamin B12 leads to an intense feeling ofwell-being in the very early days of the treatment of pemicious anaemia, it has been suggested that this vitamin could itself act as a general ‘tonic’ but there is no conclusive evidence for this effect.