Vitamin B12 absorption, dependent enzymes, and deficiency
THE CONTEXT
This passage continues the intestinal handling of vitamin B12 and explains biochemical and hematological consequences of deficiency.
Selective absorption and recycling
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Pancreatic insufficiency can contribute to vitamin B12 deficiency through excretion of cobalophilin-bound vitamin.
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Intrinsic factor binds active vitamin B12 vitamers but not other corrinoids.
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Receptors in the distal third of the ileum recognize the intrinsic factor–vitamin B12 complex, rather than free intrinsic factor or free vitamin.
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Vitamin B12 undergoes considerable enterohepatic circulation: it is excreted in bile and reabsorbed in the ileum after binding intrinsic factor.
Methylmalonyl-CoA mutase
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Methylmalonyl-CoA mutase and methionine synthase are vitamin B12-dependent enzymes.
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Methylmalonyl-CoA arises during valine catabolism and through carboxylation of propionyl-CoA. Sources of propionyl-CoA include catabolism of isoleucine, cholesterol, and odd-chain fatty acids, as well as propionate.
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Methylmalonyl-CoA mutase catalyzes the vitamin B12-dependent rearrangement of methylmalonyl-CoA to succinyl-CoA.
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Deficiency greatly reduces mutase activity, causing methylmalonyl-CoA accumulation and urinary methylmalonic acid excretion. This urinary finding provides a means of assessing vitamin B12 nutritional status.
Methionine synthase and erythropoiesis
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Vitamin B12 deficiency impairs methionine synthase, causing homocysteine accumulation and trapping folate as methyltetrahydrofolate.
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Impaired folic acid metabolism produces functional folate deficiency and disturbed erythropoiesis, with immature erythrocyte precursors entering the circulation as megaloblastic anemia.
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The passage identifies failure of vitamin B12 absorption as the most common cause of pernicious anemia.