Cyanocobalamin metabolism

Microbiological assay should stress accuracy over precision. Standardization of an assay method should include comparisons with at least one other organism having a different nutritional pattern and specificity toward the compound being assayed. Such a comparison was made for cyanocobalamin (vitamin Bi2 ) content of human blood and serum, using four microorganisms differing in their cobamide requirements and metabolism (B9). 

The metabolism of cyanide has been studied in animals. The proposed metabolic pathways shown in Figure 2-3 are (1) the major pathway, conversion to thiocyanate by either rhodanese or 3-mercapto-pyruvate sulfur transferase (2) conversion to 2-aminothiazoline-4-carboxylic acid (Wood and Cooley 1956) (3) incorporation into a 1-carbon metabolic pool (Boxer and Richards 1952) or (4) combining with hydroxocobalamin to form cyanocobalamin (vitamin B12) (Ansell and Lewis 1970). Thiocyanate has been shown to account for 60-80% of an administered cyanide dose (Blakley and Coop 1949 Wood and Cooley 1956) while 2-aminothiazoline-4-carboxylic acid accounts for about 15% of the dose (Wood and Cooley 1956). The conversion of cyanide to thiocyanate was first demonstrated in 1894. Conversion of cyanide to thiocyanate is enhanced when cyanide poisoning is treated by intravenous administration of a sulfur donor (Smith 1996 Way 1984). The sulfur donor must have a sulfane sulfur, a sulfur bonded to another sulfur (e.g., sodium thiosulfate). During conversion by rhodanese, a sulfur atom is transferred from the donor to the enzyme, forming a persulfide intermediate. The persulfide sulfur is then transferred... 

Cyanocoba/am/n- Cyanocobalamin is rapidly absorbed from IM and subcutaneous injection sites the plasma level peaks within 1 hour. Once absorbed, it is bound to plasma proteins, stored mainly in the liver and is slowly released when needed to carry out normal cellular metabolic functions. Within 48 hours after injection of 100 to 1,000 meg of vitamin B-12, 50% to 98%... 

The name vitamin B12 indicates a group of cobalt-containing corrinoids, also described as cobala-mins. Hydroxycobalamin (HOCbl), adenosylcobalamin (AdoCbl), and methylcobalamin (MeCbl) are the natural occurring forms. Instead, cyanocobalamin (Figure 19.20) is the commercially available form used for supplements and food fortification, thanks to its greater relative stability. Occasionally, sulfitocobalmin can occur in processed foods. Vitamin B,2 functions as a coenzyme and it is linked to human growth, cell development, and is involved in metabolism of certain amino acids. Vitamin B12 is present mainly in meat and diary foods, therefore a deficiency can occur in... 

Cyanocobalamin A cofactor required for essential enzymatic reactions that form tetrahydrofolate, convert homocysteine to methionine, and metabolize l-methylmalonyl-CoA Adequate supplies are required for amino acid and fatty acid metabolism, and DNA synthesis Treatment of vitamin B12 deficiency, which manifests as megaloblastic anemia and is the basis of pernicious anemia Parenteral vitamin B12 is required for pernicious anemia and other malabsorption syndromes Toxicity No toxicity associated with excess vitamin B12... 

Metabolic studies failed to detect any methylmalonyl-CoA mutase in skin fibroblasts from the first patient, while in the second patient the level was found to be 10% of normal. Two forms of vitamin B12 were tried on each of the patients, cyanocobalamin and hydroxocobalamin, both without apparent effect. 

Various vitamin B12 derivatives are shown in Figure 6.2, where the R group is usually taken as CN-. This form of vitamin B12 is cyanocobalamin. In the active coenzyme, the CN" is replaced by a 5 -deoxyriboadenosyl residue or by -CH3. Vitamin B12 seems to be the only mammalian substance that contains cobalt. It also has a unique corrin ring structure, which is very similar to that of heme. Metabolic reactions requiring vitamin B12 are discussed in Chapters 19 and 20. 

Hydrogen cyanide is metabolized through several pathways. In the major metabolic pathway (60-80% of absorbed cyanide), cyanide is converted to thiocyanate in a reaction that is catalyzed by rhodanase or 3-mercaptopyruvate sulfur transferase (Baumann et al. 1934 Himwich and Saunders 1948 Wood and Cooley 1956 Singh et al. 1989). Minor pathways include the oxidation of hydrogen cyanide or thiocyanate to carbon dioxide, reaction with cystine to form 2-aminothiazoline-4-carboxylic acid and 2-imnothizolidine-4-carboxylic acid, reaction with hydroxocobalamine to form cyanocobalamin, and conversion of hydrogen cyanide to formic acid, which enters one-carbon metabolism in the body (Wood and Cooley 1956 Boxer and Rickards 1952 Ansell and Lewis 1970 Baumeister et al. 1975). 

Small amounts of cyanocobalamin are found in the bloodstream (about 2% of total plasma vitamin B12) apparendy as part of the metabolism of cyanide derived from food (and tobacco smoke), but not in erythrocytes or tissues. If it is not converted to aquo- or hydroxocobalamin, cyanocobalamin may have antivitamin action and has been implicated in the neurological damage associated with chronic cyanide intoxication seen in parts ofwest Africa, where the dietary staple, cassava, is rich in cyanogenic glycosides. 

In addition, vitamin B12 has a role in the metabolism of cyanide, forming cyanocobalamin. This prevents the binding of cyanide to cytochrome oxidase and permits (relatively slow) metabolism to yield thiocyanate. 

Cyanocobalamin (la) is a relatively inert complex and, apart from being involved in the detoxification of small amounts of hydrogen cyanide [5], does not appear to serve any major biological function [10]. The only difference between this species and the metabolically active forms of B12 (methylcobalamin (MeCbl Ib) and 5 -deoxyadenosylcobalamin (AdoCbl Ic)) is the ligand that occupies the... 

Vitamin Bu is unique among all the vitamins in that it is the largest and most complex and because it contains a metal ion. 1 hismetal ion is cobalt. Cobalt occurs in three oxidation states Co, Co, and Co. The medicinal forms of the vitamin are cyanocobalamin and hydnoxocobalamin. In cyanocobalamin, a molecule of Cyanide is complexed to the Co atom. Cyanocobalamin is readily converted in the body to the cofactor forms methylcobalamin and 5-deoxyadenosylcobalamin. Methylcobalamin contains cobalt in the Co slate, where it acts as a cofactor for methionine synthase. 5 Deoxyadenosylcobalamin, which contains cobalt in the Co state, is the cofactor for methylmalonyl-CoA mutase. Vitamin Btj is also a cofactor for leucine aminomutase, anen7yme used in leucine metabolism (Poston, 1984). This enzyme appears not to have a vital function in metabolism. No more... 

Pernicious anaemia was a fatal disease first reported in 1880. It was not until 1926 that it was discovered that eating raw liver effected a remission. The active principle was later isolated and called vitamin B12 or cyanocobalamin. It was initially obtained from liver but during the 1960s it was noted that it could be obtained as a by-product of microbial metabolism (Table 25.2). Hydroxycobalamin is the form of choice for therapeutic use and can be derived either by chemical transformation of cyanocobalamin or directly as a fermentation product. 

Vitamin Bij (cyanocobalamin extrinsic factor) is required in folate metabolism for DNA synthesis, and a deficiency leads to pernicious anaemia. It is used to supplement the diet after certain operations that remove the site of production of intrinsic factor, such as total gastrectomy. Deficiency causes megaloblastic haemopoiesis in which there is a marked disorder of formation of erythroblasts, and can be rectified by giving hydroxocobalamin. 

The anti-pemicious-anemia vitamin. All vitamin B12 compounds contain the cobalt atom in its trivalent state. There are at least three active forms cyanocobalamin, hydroxocobalmin, nitrocobalamin. Vitamin B12is a component of a coenzyme that takes part in the shift of carboxyl groups within molecules. As such it has an influence on nucleic acid synthesis, fat metabolism, conversion of carbohydrate to fat, and... 

Most vitamins function either as a hormone/ chemical messenger (cholecalciferol), structural component in some metabolic process (pantothenic acid), or a coenzyme (phytonadi-one, thiamine, riboflavin, niacin, pyridoxine, biotin, folic acid, cyanocobalamin). At least one vitamin has more than one biochemical role. Vitamin A as an aldehyde (retinal) is a structural component of the visual pigment rhodopsin and, in its acid form (retinoic acid), is a regulator of cell differentiation. The precise biochemical functions of ascorbic acid and a-tocopherol still are not well defined. 

Patients with ileal resection commonly develop vitamin B12 deficiency, necessitating therapy with parenteral cyanocobalamin. Most other water-soluble vitamins are absorbed in the proximal jejunum, and deficits of these vitamins are found only in more severe SBS. Small bowel bacterial overgrowth can contribute to diminished vitamin B12 because bacteria may metabolize the nutrient within the intestine, decreasing its availability for absorption. SBS patients with fat malabsorption can acquire deficiencies in vitamins A, D, E, and K. These fat-soluble vitamins depend on bile salt micelles for effective absorption, and malabsorption with depletion of the bile salt pool can lead to their deficits. ... 

Cyanocobalamin (812) Deoxyadenosyl cobalamin Coenzyme in amino add metabolism... 

To search for the potential C-labeled substrate, several C compounds that were known to be metabolized by the microorganism were tested in the presence and absence of the essential nutrient in question. For the vitamin B12, we found that in the presence of guanido- C-arginine and cyanocobalamin (CN—Cbl) (27) Lactobacillus leichmannii produced the most significant amount of C02 within 16 h (Table II). Not every C-labeled compound tested was metabolized to 2 by L. leichmannii. On the other hand, U- C and 1- C glucose were metabolized even in the absence of CN—Cbl (Table II). 

Contraindications for metformin include renal insufficiency, liver disease, alcehel abuse, cardiac insufficiency, metabolic acidosis or any hypoxia-related conditien. An additional consideration is that chronic metformin therapy can decrease oral absorption and subsequent serum concentrations of cyanocobalamin (vitamin B12) nevertheless, this effect, which is seen in approximately one in four patients, dees not appear to result in anemia. 

Most media contain water-soluble B vitamins. Common to many formulations are vitamins Bi (thiamine), B2 (riboflavin), B3 (niacinamide), Bj (pantothenic acid). Be (pyridoxine), and Bg (folic acid). Biotin (vitamin H), cyanocobalamin (vitamin B]2 ), and ascorbic acid (vitamin C) are also common vitamin components. Although choline and inositol are classically grouped with vitamin components, in cell culture they function as metabolic substrates rather than as catalysts. 

Other pathways to elimination of cyanide are possible. About 1 to 2% of cyanide is lost through the lungs by exhalation. Another 15% is released by conversion to 2-aminothiazaline-4-carboxylic acid, incorporation into the one-carbon metabolic pool, or the combination with hydroxycobalamin (vitamin B,2a) to form cyanocobalamin (Pope and Rail, 1995). 

Bi2, cyanocobalamin Microorganisms, liver Propionate metabolism Poor growth, anaemia, poor coat/feathering... 

Peirce, K., Abe, T., and Cooper, B.A., 1975. Incorporation and metabolic conversion of cyanocobalamin by Ehrlich ascites carcinoma cells in vitro and in vivo. Biochimica et Biophysica Acta. 381 348-358. 

Vitamin B12 (cyanocobalamin) is a water-soluble B vitamin that acts as a coenzyme for fat and carbohydrate metabolism, protein synthesis, and hematopoiesis. 

Vitamin B12 must be converted into its coenzyme forms, adenosylcobalamin and methylcobalamin, in the cell. These coenzymes function as cofactors of methylmalonyl-CoA mutase and methionine synthase, respectively. Chronic kidney disease (CKD) may affect the conversion from vitamin B12 to the coenzyme forms. This section describes the intracellular metabolism of cyanocobalamin, which is included in many dietary supplements, in particular, referring to a recently discovered trafficking chaperone called methylmalonic aciduria cdlC type with homocystinuria (MMACHC). Cyanocobalamin is first converted to cob(II)alamin, which has no cyanogen group on the ligand occupying the upper axial position of the cobalamin structure. Cob(II)alamin is further reduced to cob(I)alamin, which can function as a coenzyme in the body. 

Our findings (Koyama el al. 1996,1997) that the smokers undergoing dialysis have peripheral neuropathy and that the fraction ratio of cyanocobalamin is comparable to that observed in patients with Leber s disease indicate the possibility of cyanide metabolism disorder in patients with CKD. In patients with CKD, thiocyanate (SCN) accumulates due to the decrease in its clearance. It impairs the major metabolic pathway of cyanide and the cyanide pool therefore increases. This increase accelerates cyanide detoxication via cyanocobalamin synthesis using vitamin B12, resulting in an increase in the... 

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