Vitamin B12 is sometimes administered parenterally to incoming feedlot cattle as a prophylactic measure. Biochem. J. Biol. [doi:10.1021/ja01614a105], Korotkova, N., Lidstrom, M., 2004. Chem., 280(11):10073–10082. The latter may be characterized by recurrent episodes of ketoacidosis, hyperammonemia, leukopenia, thrombocytopenia, and anemia, which can result in multiple organ failure and even death.262 The enzymatic defect is treated with protein restriction, cobalamin supplementation, and metronidazole to suppress microbial propionate production. Under grazing conditions, lambs are the most sensitive to cobalt deficiency, followed by mature sheep, calves, goats and mature cattle (Andrews, 1956). Vitamin B12 is a dark-red, hygroscopic, needle-shaped crystal, freely soluble in water and alcohol but insoluble in acetone, chloroform and ether. The vitamin B12 requirement increases with higher rates of animal production and metabolism. It is converted into succinyl-CoA by methylmalonyl-CoA mutase, in a reaction that requires vitamin B 12 as a cofactor. In ruminating cattle and sheep, vitamin B12 deficiency is most often caused by a cobalt deficiency. Homology modeling of human methylmalonyl-CoA mutase: a structural basis for point mutations causing methylmalonic aciduria. [doi:10.1002/pro.5560050919], Thomä, N.H., Evans, P.R., Leadlay, P.F., 2000. Soc. Rumen bacteria synthesize approximately 2 to 3 mg vitamin B12 per day when provided with adequate dietary cobalt. Brain lesions were also observed in vitamin B12 deficient lambs in that study (Vellema et al., 1999). The condition responded to two injections of vitamin B12 three weeks apart. Miyamoto E, Watanabe F, Takenaka H, Nakano Y. Biosci Biotechnol Biochem. Kinetic and thermodynamic studies on ligand substitution reactions and base-on/base-off equilibria of cyanoimidazolylcobamide, a vitamin B12 analog with an imidazole axial nucleoside. [doi:10. Milk vitamin B12 concentrations were 10 µg/ml in colostrum and early milk and declined thereafter to 50% or less the original value by 21 days of lactation (Marca et al., 1996). Metabolism of propionic acid in animal tissues. Cobalt content of the diet is the primary factor affecting the synthesis of vitamin B12 by ruminal microflora. However, Yamada et al. Flavin, M., Ortiz, P.J., Ochoa, S., 1955. Coenzyme B12-dependent ribonucleotide reductase: evidence for the participation of five cysteine residues in ribonucleotide reduction. Biochemistry, 45(30):9300–9306. Although dietary cobalt of confined livestock is usually adequate, cobalt and secondary vitamin B12 deficiency is a significant problem for grazing livestock in many areas of the world (McDowell, 2000; McDowell and Arthington, 2005). In ruminants, the rate of gluconeogenesis increases with feed intake, and one of the major substrates for gluconeogenesis is propionate. Glutamate and 2-methyleneglutarate mutase: from microbial curiosities to paradigms for coenzyme B12-dependent enzymes. 04510, Mexico, Mexico, Enrique García-Hernandez & Roberto Arreguín-Espinosa, You can also search for this author in Tissue metabolism converts cyanocobalamin to the two primary coenzyme forms, adenosylcobalamin and methylcobalamin (Ellenbogen and Cooper, 1991). Cloning, sequencing, expression, and insertional inactivation of the gene for the large subunit of coenzyme B12-dependent isobutyryl-CoA mutase from Streptomyces cinnamonensis. Vitamin B12 has good stability in premixes with or without minerals, regardless of the source of the minerals, and is little affected by pelleting (Scott, 1966; Verbeeck, 1975). 2005 Jan 19;127(2):526-7. doi: 10.1021/ja044365l. All affected individuals have episodic metabolic decompensation, usually associated with intercurrent infections or other catabolic states (e.g., surgery). [doi:10.1074/jbc.M107232200], Booker, S., Licht, S., Broderick, J., Stubbe, J., 1994. Chem., 283(47):32283–32293. McDowell and Arthington (2003) have presented an extensive review of cobalt nutrition. As discussed earlier, propionic acid is converted by PCC to d-methylmalonyl-CoA. Biogenesis of the mitochondrial enzyme methylmalonyl CoA mutase. Chem., 285(49):38204–38213. Liver cobalt concentrations in the range of 0.05 to 0.07 mg per kg (ppm; dry basis) or below are critical levels indicating deficiency (McDowell, 1985). Plasma MMA concentrations remained below 2 µmol/liter, considered normal for sheep. The existence of human methylmalonic acidemia (MMA) due to the presence of mutations in MCM shows the importance of its role in metabolism. 04510, Mexico) In humans, instead of the "vitamin", two organometallic B12-forms are coenzymes in two metabolically important enzymes: Methyl-cobalamin, the cofactor of methionine synthase, and coenzyme B12 (adenosyl-cobalamin), the cofactor of methylmalonyl-CoA mutase. Structure of vitamin B12. Rosenblatt, D., Fenton, W., 2001. PNAS, 106(51):21567–21572. J. Biol. Chem., 281(26):17838–17844. Life Sci., 57(1):106–127. Biophys., 370(1):138–141. Many forages and concentrate feeds do not supply adequate (0.10-0.20 ppm) cobalt, and thus supplementation is required. In humans, instead of the "vitamin", two organometallic B12-forms are coenzymes in two metabolically important enzymes: Methyl-cobalamin, the cofactor of methionine synthase, and coenzyme B12 (adenosyl-cobalamin), the cofactor of methylmalonyl-CoA mutase. Primiparous and multiparous cows differed in their milk yield response to dietary cobalt supplementation (Kincaid et al., 2003). shermanii has helped to elucidate the role of this cofactor AdoCbl in the reaction to specify the mechanism by which radicals are generated from the coenzyme and to clarify the interactions between the enzyme, coenzyme, and substrate. 46-2), which is used for methylation reactions in the central nervous system. (1999). Restricted roughage rations have been reported to increase vitamin B12 levels in rumen fluid and serum, reduce milk and liver concentrations and increase urinary excretion compared to cows fed roughage ad libitum (Walker and Elliot, 1972). The effects of folic acid and vitamin B12 on lactation performance were not mainly explained by methionine economy because of a more efficient methylneogenesis but were rather related to increased glucose availability and changes in methionine metabolism (Preynat et al., 2009, a, b; 2010). Assay was based on the rate of utilization of enzymatically prepared, chromatographically purified 14C carboxy-labeled racemic methylmalonyl-CoA. Although dietary supplementation of cobalt is the normal means of meeting the vitamin B12 requirement of ruminants, parenteral administration is used to treat animals with apparent deficiency symptoms or the general appearance of malnutrition or poor health. | Plants grown on soil containing 15 ppm cobalt with neutral or slightly acid pH can contain more cobalt than plants grown with 40 ppm cobalt and an alkaline pH (Latteur, 1962). Med., 348(23): 2304–2312. Identification of the gene responsible for the cblA complementation group of vitamin B12 responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements. McDowell, University of Florida. Substantial amounts of vitamin B12 are secreted into the duodenum and reabsorbed in the ileum, a process that is presumably subject to regulation based on the vitamin B12status of the animal. (1981) did not detect any effect of supplementary vitamin B12 on milk fat synthesis in dairy cows. Normal concentrations of serum MMA are tentatively suggested as being less than 2 µmol per liter, while subclinical cobalt deficiency is indicated by serum MMA concentrations of 2 to 4 µmol per liter and outright cobalt deficiency by more than 4 µmol per liter of serum (Paterson and MacPherson, 1990). Methylmalonic acidemia is caused by a deficiency in methylmalonyl-CoA mutase, which functions in the conversion of methionine, isoleucine, and valine to succinyl-CoA (see Fig. However, these materials are also a source of anti-vitamin B12. [doi:10.1007/s10295-006-0094-3], Reitzer, R., Gruber, K., Jogl, G., Wagner, U.G., Bothe, H., Buckel, W., Kratky, C., 1999. Results from a multi-center prospective registry. Distribution of coenzyme B12-dependent diol dehydratase and glycerol dehydratase in selected genera of Enterobacteriaceae and Propionibacteriaceae. Plants have varying degrees of affinity for cobalt, some being able to concentrate the element much more than others. Chem., 277(21):18523–18527. [doi:10.1074/jbc.M704850200], Janata, J., Kogekar, N., Fenton, W., 1997. The cytoplasmatic methionine synthase catalyzes the transfer of a methyl group from N-methyl-tetrahydrofolate to homocysteine to yield methionine and to liberate tetrahydrofolate. [doi:10.1039/CS9962500329], Article This suggests that the MAT does not discriminate against R-substituted acyl-CoA thioesters solely on the basis of substrate size. Pernicious anemia in humans is caused by a lack of the intrinsic factor. General functions of vitamin B12 are to promote red blood cell synthesis and to maintain nervous system integrity, which are functions noticeably affected in the deficient state (McDowell, 2000). In the presence of added dAB12 (100 to 500 ng) activities were: group I, 0.091 (0.018 to 0.190), group II, 0.093 (0.005 to 0.308), and group III, 0.232 ± 0.135 (0.090 to 0.510) nmole/mg leukocyte protein per hr. Likewise, serum B12levels were higher in primiparous than multiparous cows. [doi:10.1074/jbc. Liver and kidney are especially rich sources. Synthesis of this vitamin in the alimentary tract is of considerable importance for animals (McDowell, 2000; McDowell and Arthington, 2005). | J. Biol. It is still necessary to study the mechanisms involved in more detail using new methods. Milk is a good source of vitamin B12. Girard and coworkers have begun to explore the effects of vitamin B12, folic acid and methionine metabolism in lactating dairy cows (Girard et al., 1998; Girard and Matte, 2005; Preynat et al., 2009a, b; 2010; Girard et al., 2009). [doi:10.1002/hlca.200390313], Ledley, F., Lumetta, M., Nguyen, N., Kolhouse, F., Allen, R., 1988. Plant products are practically devoid of vitamin B12. This enzyme catalyzes the reversible isomerization of L-methylmalonyl-CoA to succinyl-CoA using adenosylcobalamin (AdoCbl) as a cofactor … Interrelationships exist with dietary cobalt, choline, methionine and folic acid. Synthesis and processing of a precursor in a cell system and in cultures cells. Experiments with sheep suggest an oral requirement for growing lambs of about 200 µg per day, about 10 times the reported oral requirement of other species per unit of food intake (Marston, 1970). PNAS, 44(11):1093–1097. HHS The comparatively high cobalt requirement of ruminants arises partly from the low efficiency of production of vitamin B12 from cobalt by the rumen microflora and partly from the low efficiency of absorption of vitamin B12 (McDowell, 2000). eLS, John Wiley & Sons, Ltd. [doi:10.1038/npg.els.0000666], Banerjee, R., Vlasie, M., 2002. [doi:10.1021/bi036299q], Vlasie, M., Chowdhury, S., Banerjee, R., 2002. Chem. Lehninger, A., Nelson, D., Cox, M., 1993. [doi:10.1038/176823a0], Forage, R., Foster, M., 1979. Croom et al. Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. PubMed Google Scholar. Based upon performance and blood measures, the cobalt requirement for fattening cattle may be between 0.15 and 0.25 mg per kg (0.068 to 0.114 mg per lb) (Stangl et al., 2000a, b; Tiffany et al., 2003).
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