Vitamin B12 is Found only in Foods of Animal Origin
المؤلف:
Peter J. Kennelly, Kathleen M. Botham, Owen P. McGuinness, Victor W. Rodwell, P. Anthony Weil
المصدر:
Harpers Illustrated Biochemistry
الجزء والصفحة:
32nd edition.p544-545
2025-12-18
65
The term “vitamin B12 ” is used as a generic descriptor for the cobalamins—those corrinoids (cobalt-containing compounds possessing the corrin ring) having the biological activity of the vitamin (Figure 1). Some corrinoids that are growth factors for microorganisms not only have no vitamin B12 activity, but may also be antimetabolites of the vitamin. Although it is synthesized exclusively by microorganisms, for practical purposes vitamin B12 is found only in foods of animal origin, there being no plant sources of this vitamin. This means that strict vegetarians (vegans) are at risk of developing B12 deficiency. The small amounts of the vitamin formed by bacteria on the surface of fruits may be adequate to meet requirements, but preparations of vitamin B12 made by bacterial fermentation are available.
Fig1. Vitamin B12 .Four coordination sites on the central cobalt atom are chelated by the nitrogen atoms of the corrin ring, and one by the nitrogen of the dimethylbenzimidazole nucleotide. The sixth coordination site may be occupied by CN− (cyanocobalamin), OH− (hydroxocobalamin), H2 O (aquocobalamin, —CH3 (methyl cobalamin), or 5′-deoxyadenosine (adenosylcobalamin).
Vitamin B12 Absorption Requires Two Binding Proteins
Vitamin B12 is absorbed bound to intrinsic factor, a small glycoprotein secreted by the parietal cells of the gastric mucosa. Gastric acid and pepsin release the vitamin from protein binding in food and make it available to bind to cobalophilin, a binding protein secreted in the saliva. In the duodenum, cobalophilin is hydrolyzed, releasing the vitamin for binding to intrinsic factor. Pancreatic insufficiency can therefore be a factor in the development of vitamin B12 deficiency, resulting in the excretion of cobalophilin-bound vitamin B12 . Intrinsic factor binds only the active vitamin B12 vitamers and not other corrinoids. Vitamin B12 is absorbed from the distal third of the ileum via receptors that bind the intrinsic factor–vitamin B12 complex, but not free intrinsic factor or free vitamin. There is considerable enterohepatic circulation of vitamin B12 , with excretion in the bile, then reabsorption after binding to intrinsic factor in the ileum.
There Are Two Vitamin B12–Dependent Enzymes
Methylmalonyl-CoA mutase, and methionine synthase (Figure 2) are vitamin B12–dependent enzymes. Methyl malonyl-CoA is formed as an intermediate in the catabolism of valine as well as by the carboxylation of propionyl-CoA arising from the catabolism of isoleucine, cholesterol, and fatty acids with an odd number of carbon atoms, or propionate, a major product of microbial fermentation ruminants. Methylmalonyl CoA undergoes a vitamin B12–dependent rearrangement to succinyl-CoA, catalyzed by methylmalonyl-CoA mutase. The activity of this enzyme is greatly reduced in vitamin B12 deficiency, leading to an accumulation of methylmalonyl-CoA and urinary excretion of methylmalonic acid, which provides a means of assessing vitamin B12 nutritional status.
Fig2. Homocysteine and the folate trap. Vitamin B12 deficiency leads to impairment of methionine synthase, resulting in accumulation of homocysteine and trapping folate as methyltetrahydrofolate.
Vitamin B12 Deficiency Causes Pernicious Anemia
Pernicious anemia arises when vitamin B12 deficiency impairs the metabolism of folic acid, leading to functional folate deficiency that disturbs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The most common cause of pernicious anemia is failure of the absorption of vitamin B12 rather than dietary deficiency. This can be the result of failure of intrinsic factor secretion caused by autoimmune disease affecting parietal cells or from production of anti-intrinsic fac tor antibodies. There is irreversible degeneration of the spinal cord in pernicious anemia, as a result of failure of methylation of one arginine residue in myelin basic protein. This is the result of methionine deficiency in the central nervous system, rather than secondary folate deficiency.
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