Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein. Biochem., 269(18): 4484–4494. Cloning, sequencing, expression, and insertional inactivation of the gene for the large subunit of coenzyme B12-dependent isobutyryl-CoA mutase from Streptomyces cinnamonensis. This enzyme works with vitamin B12 (also called cobalamin) to break down several protein building blocks (amino acids), certain lipids, and cholesterol. The first discernible response to feeding cobalt or parenteral vitamin B12is a rapid improvement in appetite and body weight. J. Biol. Fatty liver, hemosiderized spleen and hypoplasia of the erythrogenic tissue of bone marrow are also characteristic (Filmer, 1933). [doi:10.1093/hmg/6.9.1457], Jansen, R., Kalousek, F., Fenton, W., Rosenberg, E., Ledley, F., 1989. Toraya, T., Kuno, S., Fukui, S., 1980. Cobalamin is an essential vitamin that is not synthesized in the human body and requires proper supplementation from meats and dairy products. 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. In addition, in the human mitochondria an adenosyl-transferase incorporates the organometallic group of coenzyme B12. An additional function of vitamin B12 relates to immune function. Struct. [doi:10.1074/jbc.M704850200], Janata, J., Kogekar, N., Fenton, W., 1997. Biochemistry, 38(25):7999–8005. Project (No. Chem. Journal of Nutrition. Biophys., 370(1):138–141. These natural analogs have little or no vitamin B12 activity. Root nodules of certain legumes contain small quantities of vitamin B12. J. Biol. Implications for decoding the human genome. New type of a natural corrinoid. PubMed Epub 2011 Jun 20. No correlation was apparent between leukocyte mutase ativities of the vitamin B12-deficient subjects and the excretion of urinary methylmalonate, the severity of the anemia, or the presence of neurological impairment of the vitamin B12-deficiency state. In the mitochondrial methylmalonyl-CoA mutase a radical process transforms methylmalonyl-CoA (a remains e.g. The highest enzyme activity for methylmalonyl-CoA hydrolysis (approximately 3 units/mg of protein) is obtained at pH 6, indicating a much different pH optimum relative to that for (S)-HIB-CoA.2 A d-(S)-methylmalonyl-CoA hydrolase has also been purified from rat liver and partially characterized.13,14 The characteristics of this enzyme including pH profile, specific activity for the hydrolysis of methylmalonyl-CoA, molecular weight of the enzyme, and enzyme binding properties on ion-exchange columns are all quite similar to those of HIB-CoA hydrolase. - 185.122.202.74. Vitamin B12 is only slightly sensitive to heat, oxygen, moisture and pH (Gadient, 1986). Animals can tolerate large excesses of vitamin B12. Treatment of pernicious anemia by a special diet. Article In ruminants, the rate of gluconeogenesis increases with feed intake, and one of the major substrates for gluconeogenesis is propionate. There is no convincing evidence that the vitamin is produced in the tissues of of animals. 110:1338-1346 Gaire, D, et al. [doi:10.1021/ ja0503736], Buckel, W., Golding, B., 1996. Young ruminants require supplemental vitamin B12 prior to full rumen development. Precise estimates of minimum cobalt requirements are difficult because of the influence of variables such as seasonal changes in herbage cobalt concentrations, selective grazing and soil properties. The net effect of each is to block the conversion of methylmalonyl-CoA to succinyl-CoA. Structure, 6(6): 711–720. Met Ions Life Sci. Methylmalonyl-CoA, in turn, is formed from propionyl-CoA in a previous conversion step – a step which requires biotin and magnesium (1). In further studies, supplemental vitamin B12 and folic acid were found to be beneficial for milk production and milk component yields for high producing dairy cows in early lactation (Girard and Matte, 1998; 2005; Girard et al., 2005; 2009; Preynat et al., 2009 a, b; 2010). d-Methylmalonyl-CoA is then converted by methylmanolyl-CoA epimerase (encoded by the gene MCEE on chromosome 2p13.3) into l-methylmalonyl-CoA, which is in turn converted in a reversible reaction to succinyl-CoA in a reaction catalyzed by the mitochondrial 5-adenosylcobalamin (B12)-dependent enzyme, methylmalonyl-CoA mutase (MCM), encoded by the MUT gene on chromosome 6p12.3. Supply of methionine, because of its role as donor of preformed labile methyl groups, affects the needs for methylneogenesis (Bailey and Gregory, 1999) and consequently, for folic acid and vitamin B12. J. J. Biol. The crystal structure of class II ribonucleotide reductase reveals how an allosterically regulated monomer mimics a dimmer. Methylmalonyl-CoA is then isomerized in succinyl-CoA under the action of the vitamin B12-dependent enzyme, methylmalonyl-CoA mutase. Tax calculation will be finalised during checkout. [doi:10. 10:56-62. Cobalamin is a compound of four pyrrole rings and central cobalt ion. Comparison of two methods for the measurement of rat liver methylmalonyl-coenzyme A mutase activity: HPLC and radioisotopic assays. All these compounds contain a cobalt atom stabilized within a corrin ring structure that is similar to the porphyrin ring of hemoglobin and the cytochromes (Ellenbogen and Cooper, 1991). 12-6). The undosed half had the following performance for the 14 years: in 2 years, lambs were unthrifty, but there were no deaths; in 3 years, growth rate of the lambs was slightly retarded; in 4 years, 30% to 100% of the lamb crop was lost; in 5 years, the performance of the remaining stock was as good as that of dosed animals. J. Later, in the duodenum, it is liberated by trypsin where it binds to the intrinsic factor produced by the parietal cells of the stomach. Milk is a good source of vitamin B12. Commercial sources of vitamin B12 are produced by fermentation and are available as cyanocobalamin. This site needs JavaScript to work properly. Increasing dietary cobalt supply increases production of these analogs in the rumen at the expense of the biologically active forms of the vitamin. These reactions explain the rise of both methylmalonic acid and homocysteine in PA, and when this disease is suspected, these should be tested even in patients with normal B12 levels, particularly when the erythrocyte MCV is high. [doi:10.1021/bi00208a019]. [doi:10.1021/bi0004302], Tobimatsu, T., Sakai, T., Hasida, Y., Mizoguchi, N., Miyoshi, S., Toraya, T., 1997. 46-2), which is used for methylation reactions in the central nervous system. [doi:10.1074/jbc.M600047200], Peters, H., Nefedov, M., Salsero, J., Pitt, J., Fowler, K., Gazeas, S., Kahler, S., Ioannou, P., 2003. The crystal structure of coenzyme B12-dependent glycerol dehydratase in complex with cobalamin and propane-1,2-diol. Onset of MMA ranges from the neonatal period through adulthood, and the phenotypic severity varies considerably. Learn more Acute metabolic decompensation episodes are treated as discussed for propionic acidemia above. Peters and Elliot (1983) reported that vitamin B12 injections increased milk protein production, but not milk yield, solids or fat production in vitamin B12-deficient ewes during early lactation. Immunochemical evidence for the difference between coenzyme-B12-dependent diol dehydratase and glycerol dehydratase. Half the ewes, replacements and progeny received supplemental cobalt and remained healthy (in no particular order by years). Thus, vitamin B12 status affects the metabolism of choline and its derivatives, and the synthesis of the purines and pyrimidines, components of DNA and RNA. [doi:10.1128/JB.184.6.1750-1758.2002]. Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Cochrane Database Syst Rev. Conformational changes on substrate binding to methylmalonyl CoA mutase and new insights into the free radical mechanism. CAS However, these materials are also a source of anti-vitamin B12. J. Biol. Kominato (1971) reported a tissue half-life of 32 days for vitamin B12, indicating considerable tissue storage. The conclusion would be that if there was no benefit from cobalt supplementation in a particular year, there was no guarantee that in the following year that a moderate to severe cobalt deficiency would not occur (McDowell, 2000). COVID-19 is an emerging, rapidly evolving situation. M111.320051], Cracan, V., Padovani, D., Banerjee, R., 2010. Biochim. Importance of the histidine ligand to coenzyme B12 in the reaction catalyzed by methylmalonyl CoA mutase. Children with complete mutase deficiency have the poorest prognosis and frequently die during an acute episode. Chem., 273(11):6508–6517. [doi:10.1016/S0969-2126(99) 80116-6], Rickes, E., Brink, N., Koniuszy, F., Wood, T., Folkers, K., 1948.