Cobalamin vitamin absorption

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. 

Cobalt has no confirmed nutritional role in mammalian organisms aside from its participation in the corrin ring structure of cobalamins (vitamin B12). Nonetheless, inorganic cobalt is absorbed by the intestine. That this absorption pathway was shared with iron was first suggested by the observation of a mineral-mineral competition 42). The use of radioisotopes of iron in diagnostic tests of absorption for characterizing iron nutrition in human subjects has been advanced (43-45). An excellent correlation between absorption of radioiron and radiocobalt has been reported (43-45). 

Seetharam, B., and Alpers, D.H., 1982. Absorption and transport of cobalamin (vitamin Bn). Annual Review of Nutrition. 2 343-369. 

Radioisotope dilution assays are based on the principle of competition between radioactive labeled ( Co) vitamin B 2 and cobalamins extracted from matrices for binding sites on the intrinsic factor (a glycoprotein). Binding is in proportion to the concentration of the radioactive and nonradio active B 2 with the concentration of intrinsic factor as the limiting factor. Free cobalamins are separated from those bound on the intrinsic factor by absorption... 

Spectrophotometric deterrnination at 550 nm is relatively insensitive and is useful for the deterrnination of vitamin B 2 in high potency products such as premixes. Thin-layer chromatography and open-column chromatography have been appHed to both the direct assay of cobalamins and to the fractionation and removal of interfering substances from sample extracts prior to microbiological or radioassay. Atomic absorption spectrophotometry of cobalt has been proposed for the deterrnination of vitamin B 2 in dry feeds. Chemical methods based on the estimation of cyanide or the presence of 5,6-dimethylben2irnida2ole in the vitamin B 2 molecule have not been widely used. 

Vitamin B12 is special in as far as its absorption depends on the availability of several secretory proteins, the most important being the so-called intrinsic factor (IF). IF is produced by the parietal cells of the fundic mucosa in man and is secreted simultaneously with HC1. In the small intestine, vitamin B12 (extrinsic factor) binds to the alkali-stable gastric glycoprotein IF. The molecules form a complex that resists intestinal proteolysis. In the ileum, the IF-vitamin B 12-complex attaches to specific mucosal receptors of the microvilli as soon as the chymus reaches a neutral pH. Then either cobalamin alone or the complex as a whole enters the mucosal cell. 

Oral vitamin B12 supplementation appears to be as effective as parenteral, even in patients with pernicious anemia, because the alternate vitamin B12 absorption pathway is independent of intrinsic factor. Oral cobalamin is initiated at 1 to 2 mg daily for 1 to 2 weeks, followed by 1 mg daily. 

The most likely reason for cobalamin deficiency is pernicious anemia (failure to absorb vitamin B 2 in the absence of intrinsic factor from parietal cells). Vitamin Bjj absorption also decreases with aging and in individuals with chronic pancreatitis. Less common reasons for Bjj deficiency include a long-term completely vegetarian diet (plants don t contain vitamin Bjj) and infection with Diphyllobothrium latum, a parasite found in raw fish. Excess vitamin B,2 is stored in the body, so deficiencies develop slowly. 

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. 

Strict vegetarian diet or after diseases affecting cobalamin absorption. The main effects of vitamin deficiency are pernicious anemia, macrocytosis, and neurological problems. A particularity of this vitamin is that it can be stored especially in the liver and kidneys. 

The answer is D. Several vitamin deficiencies can cause anemia due to reduced DNA synthesis in the erythropoietic cells of the bone marrow, especially folic acid and vitamin Bj2 (cobalamin), which are particularly prevalent among elderly patients due to poor diet and reduced absorption. In addition, deficiencies of either folic acid or vitamin Bj2 could produce the megaloblastic anemia seen in this patient. However, the absence of neurologic symptoms, a hallmark of vitamin Bj2 deficiency, makes that diagnosis less likely than folic acid deficiency. 

Cobalt must be supplied in the diet in its physiologically active form, vitamin B12. GI absorption of cobalt is about 25%, with wide individual variation excretion occurs mainly via the urine. The major part is excreted within days and the rest has a biological half-life of about two years. Originally, the therapy for pernicious anemia was to have patients eat large amounts of liver. The most reliable treatment now is monthly injections of cobalamin. 

Role of Cobalamin in Amino Acid Catabolism Pernicious anemia is caused by impaired absorption of vitamin Bi2. What is the effect of this impairment on the catabolism of amino acids Are all amino acids equally affected (Hint see Box 17-2.)... 

Oral vitamin Bj2 supplementation appears to be as effective as parenteral, even in patients with pernicious anemia, because the alternate vitamin Bj2 absorption pathway is independent of intrinsic factor. Oral cobalamin is initiated at 1 to 2 mg daily for 1 to 2 weeks, followed by 1 mg daUy. Parenteral therapy is more rapid acting than oral therapy and should be used if neurologic symptoms are present. A popular regimen is cyanocobalamin 1,000 meg daily for 1 week, then weekly for 1 month, and then monthly. When symptoms resolve, daily oral administration can be initiated. 

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. 

The human Bu-binder intrinsic factor is a glycoprotein of ca. 44kDa, with a high binding constant (in 1 1 complexes) for vitamin B12 (1) and other cobalamins. The intrinsic factor is secreted by cells of the gastric mucosa and specifically binds cobalamins and carries them to the ileum. There the ileum receptor protein accepts the corrinoid from the intrinsic factor complex and transports it further across the intestinal epithelial absorptive cell. The cobalamins then appear to be bound to transcobalamin II and transported in the blood in this way to membrane-bound transcobalamin/corrin receptor proteins of the specific cells. ... 

Herbert, V., Fong, W, Guile, V, and Stopler, T. (1990. Low holotranscobalamin II is the earliest serum marker for subnormal vitamin Bn (cobalamin) absorption in patients with AIDE. Am. ]. Hematol. 34,132-139. 

Intestinal malabsorption of vitamin B12 may be caused by gastrectomy or ileal resection, with an inverse relationship between the length of ileum resected and the absorption of vitamin B12. Other causes of malabsorption are tropical sprue, inflammatory disease of the small intestine, intestinal stasis with overgrowth of colonic bacteria, which consume the vitamin 6,2 ingested by the host, and HIV infection. Another cause of vitamin B malabsorption is failure to extract cobalamin from food. Some patients fail to absorb cobalamin bound to food, whereas absorption of nonfood-bound cobalamin in the Schilling test is unimpaired. This is particularly a problem in patients with compromised gastric status or early in the course of development of pernicious anemia. 

TCI has a high affinity for and is about 90% saturated with cobalamin, while TCIII binds less strongly and is largely unsaturated. However, TCII binds newly absorbed cobalamins, and the TCII-cobalamin complex appears to deliver cobalamin to peripheral tissues (Figure 38-18). TCII accounts for most of the unsaturated vitamin B12 binding capacity of serum. Therefore, cobalophilins (except TCII see below) probably have a minimal role in cobalamin absorption, transport, and metabolism. Thus, members of the family with congenital cobalophilin deficiency showed no symptoms of vitamin B12 deficiency despite a very low serum concentration of the vitamin secondary to the absence of TCI. 

After the stomach s acidic environment facilitates the breakdown of vitamin B12 bound to food, the vitamin B12 binds to the intrinsic factor released by the stomach s parietal cells. The secretion of intrinsic factor generally corresponds to the release of hydrochloric acid and serves as a cell-directed carrier protein similar to transferrin for iron. This complex, resistant to degradation, forms in the duodenum and allows for subsequent absorption of vitamin B12 in the terminal ileum. The cobalamin-intrinsic factor complex is taken up into the ileal mucosal cell, the intrinsic factor is discarded, and the cobalamin is transferred to transcobalamin It, which serves as a transport protein. This complex is secreted into the circulation and is taken up by the fiver, bone marrow, and other cells. Transcobalamin 11 has a short half-fife of 1 hour and is rapidly cleared from the blood. Consequently, most circulating cobalamin is bound to serum haptocorrins (formerly transcobalamin I and transcobalamin IB) whose function is unknown. However, it should be noted that an alternate pathway for vitamin B12 absorption independent of intrinsic factor or an intact ter-... 

Figure 42-2. Absorption, transport and storage of vitamin Bj. IF = intrinsic factor, a glycoprotein secreted by gastric parietal cells TC = transcobalamins, blood proteins that carry cobalamin to the Uver. (Reproduced, with permission, from D.B. Marks, et al. Basic Medical Biochemistry A Clinical Approach. Philadelphia Lippincott Williams Wilkins, 1996 619.)...

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