Cobalamins special

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. 

There is some evidence that the iron-sulfur protein, FhuF, participates in the mobilization of iron from hydroxamate siderophores in E. coli (Muller et ah, 1998 Hantke, K. unpublished observations). However, a reductase activity of FhuF has not been demonstrated. Many siderophore-iron reductases have been shown to be active in vitro and some have been purified. The characterization of these reductases has revealed them to be flavin reductases which obtain the electrons for flavin reduction from NAD(P)H, and whose main functions are in areas other than reduction of ferric iron (e.g. flavin reductase Fre, sulfite reductase). To date, no specialized siderophore-iron reductases have been identified. It has been suggested that the reduced flavins from flavin oxidoreductases are the electron donors for ferric iron reduction (Fontecave et ah, 1994). Recently it has been shown, after a fruitless search for a reducing enzyme, that reduction of Co3+ in cobalamin is achieved by reduced flavin. Also in this case it was suggested that cobalamins and corrinoids are reduced in vivo by flavins which may be generated by the flavin... 

Cobalamine can only be resorbed in the small intestine when the gastric mucosa secretes what is known as intrinsic factor—a glycoprotein that binds cobalamine (the extrinsic factor) and thereby protects it from degradation. In the blood, the vitamin is bound to a special protein known as trans-cobalamin. The liver is able to store vitamin Bi2 in amounts suf cient to last for several months. Vitamin B12 deficiency is usually due to an absence of intrinsic factor and the resulting resorption disturbance. This leads to a disturbance in blood formation known as pernicious anemia. 

A special mention13 may be made of cobalt complexes the [Co(HDMG)2] (w = 0, 1) has been named cobaloxime by analogy with cobalamin , which is another name of vitamin B,2. 

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 B,. Vitamin Bi2 the colloquial name for cobalamin (Cbl), is a large polar molecule that must be bound to specialized transport proteins to gain entry into cells. After oral administration it is bound to intrinsic factor (IF), a protein released from the parietal cells in the stomach and proximal cells in the duodenum. The Cbl-IF complex binds to an IF-receptor located on the surface of the ileum, which triggers a yet undefined endocy-totic process. After internalization, the fate of the IF-Cbl complex has yet to be clarified. It vvas reported that IF-Cbl complex dissociates at acidic pH, and Cbl is transferred to transco-balamin II by Ramasamy and coworkers (94), whereas Dan and Cutler (95) found evidence of free Cbl in endosomes and the basolateral side of the membrane after administration to the apical surface of Caco-2 cell monolayers. It is clear, however, that Cbl is transported into all other cells only when bound to transcobal-amin II. 

Adenosyl-cobalamine catalyzes hydrogen shifts as a special isomerisation reaction. With exception of reduction of ribonucleotides the H-shift occurs intramolecularly. Methyl-cobalamine and tetrahydrofolic add are the coenzymes in methylating homocysteine to methionine. 

As apparent from the description above, a number of different assays are available for the measurement of cobalamin. Some are commercially available and some are in-house methods. In order to make an educated choice concerning the method to be used, a number of issues need to be considered. Many of these are linked to the standard characteristics of the assays concerning sensitivity, specificity imprecision, practicability and costs. The number of samples to be analysed per year as well as the availability of specialized equipment will also highly influence the choice of method. 

Animals, plants, and fungi are incapable of producing cobalamin it is the only vitamin that is exclusively produced hy microorganisms, particularly by anaerobes (Roth et al. 1996 Martens et al. 2002 Smith et al. 2007). Furthermore, biochemical and genomic data indicate that only a few bacteria and archaea possess the abOity to produce this vitamin (Roth et al. 1996 Rodionov et al. 2003). Adult ruminant animals and strict vegetarians can obtain the vitamin in specialized bacteria present in the rumen. Humans do not have such microbiota in their small intestine and must absorb the co-enzyme from natural sources such as animal meats (especially liver and kidney), fish, eggs, and pharmaceutical products (Herbert 1996). 

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