Absorption, dietary cobalamins

Intestinal Receptor for IF-B 2 Complex. Although this receptor is not, strictly speaking, a cobalamin-binding protein, it is essential for normal absorption of dietary cobalamin. It is present on the membrane of microvilli of ileal but not jejunal or duodenal cells, with the highest concentration in the distal 60-cm portion of the small intestine. The purified receptor is composed of two subunits (M.W. 90,(X)0 and 140,000) and binds free IF and IF-B12 complex, although free IF binds more slowly. Subsequent transport of cobalamin into enterocytes is accomplished by an active process. 

Dietary cobalamin is absorbed from animal food sources by a multistage process shown in Figure 42-2. Cobalamin absorption requires the presence of a protein (the intrinsic factor, IF) secreted from the parietal cells of the stomach to bind cobalamin and aid in its absorption in the ileum. The protein is released into the ileum while the cobalamin is transported to the blood stream where it binds specialized serum proteins, the transcobalamins (TC), which transport it to other tissues such as liver where cobalamin can be stored (usually several milligrams are present in liver). In the absence of the intrinsic factor... 

Vitamin B12 deficiency is rarely caused by a lack of Bn in the diet, but is rather attributed to various absorption and transport disorders. Howard et al. (1998) investigated dietary cobalamin intake among elderly people with an abnormal cobalamin status and concluded that the high frequency of mildly abnormal cobalamin levels could not be attributed to poor intake of the... 

On the ingestion of a physiologic quantity of cobalamin, a series of specific events occur in a sequential fashion to ensure appropriate and adequate absorption. First, cobalamin is released from dietary proteins, whereon the salivary R proteins ensure intragastric binding of the substance. Thereafter, intraduodenal digestion of the R protein cobalamin complexes occurs, particularly by pancreatic proteases, which are responsible for the release of cobalamin. Once cobalamin is free within the duodenum or upper small bowel, binding of the vitamin by intrinsic factor occurs before its transport to the lower ileum. At this point, the intrinsic factor-bound cobalamin is attached to the apical membrane of the ileum cells, and absorption via specific receptor-mediated pathways occurs. The transcellular transport of cobalamin in the ileal mucosa is a slow process and presumably involves endocytosis. The vitamin is thereafter released into the portal circulation and passes to the liver for processing. 

Dietary deficiency in the absence of absorption defects can be effectively reversed with oral supplementation of 1 p.m of vitamin B 2 daily. If deficiency is related to a defect in vitamin absorption, daily doses of 1 pg adininistered subcutaneously or intramuscularly are effective (33). However, a single intramuscular dose of 100 pg of cobalamin once per month is adequate in patients with chronic gastric or ileal damage. Larger doses are generally rapidly cleared from the plasma into the urine and are not effective unless the patient demonstrates poor vitamin retention. 

Vitamin Bn deficiency Deficiency, although rare, results in two serious problems megaloblastic anaemia (which is identical to that caused by folate deficiency) and a specific neuropathy called Bi2-associated neuropathy or cobalamin-deficiency-associated neuropathy (previously called, subacute combined degeneration of the cord). A normal healthy adult can survive more than a decade without dietary vitamin B12 without any signs of deficiency since it is synthesised by microorganisms in the colon and then absorbed. However, pernicious anaemia develops fairly rapidly in patients who have a defective vitamin B12 absorption system due to a lack of intrinsic factor. It results in death in 3 days. Minot and Murphy discovered that giving patients liver, which contains the intrinsic factor, and which is lightly cooked to avoid denaturation, cured the anaemia. For this discovery they were awarded the Nobel Prize in Medicine in 1934. 

Considerably more intrinsic factor is secreted than is needed for the binding and absorption of dietary vitamin B12, which requires only about 1 % of the total intrinsic factor available. There is a considerable enterohepatic circulation of vitamin B12, variously estimated as between 1 to 9 /rg per day, about the same as the dietary intake. Like dietary vitamin B12 bound to salivary cobalophilin, the biliary cobalophUins are hydrolyzed in the duodenum, and the vitamin released binds to intrinsic factor, thus permitting reabsorption in the Ueum. Whereas cobalophUins and transcorrin III have low specificity, and wUl bind a variety of corrinoids, intrinsic factor orUy binds cobalamins, and only the biologicaUy active vitamin wiU be reabsorbed to any significant extent. 

B. Megaloblastic anemia is caused by a decrease in the synthesis of deoxythymidylate and the purine bases usually caused by a deficiency in either THF or cobalamin or both. This results in decreased DNA synthesis, which results in abnormally large hematopoietic cells created by perturbed cell division and DNA replication and repair. This patient exhibits signs of chronic alcoholism, which often leads to a folate deficiency. This can occur due to poor dietary intake, decreased absorption of folate due to damage of the intestinal brush border cells and resulting conjugase deficiency, and poor renal resorption of folate. 

Elderly people 40 subjects (19M) frequently suffering from vitamin B12 deficiency (>20%), often neither identified nor investigated because of its subclinical manifestations, or mainly caused by reduced production or lack of intrinsic factor (15-20%), or altered cobalamin absorption, or possibly associated with insufficient dietary intake. 

Cobalamin is the anti-pernicious anemia factor. Minutest amounts (a few micrograms) cure pernicious anemia in man. The disease is characterized by a drastic decrease of the erythrocyte count (due to a disturbance in the maturation of red blood cells). Pernicious anemia does not arise from a dietary deficiency, but rather is caused by a defect in the absorption of the vitamin. Cobalamin (designated the extrinsic factor, in this connection) can be taken up by the human organism only in the presence of the intrinsic factor, a mucoprotein. The latter is formed in the gastric mucosa its absence causes pernicious anemia. 

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