methylmalonyl coa mutase


Summary: An enzyme that catalyzes the conversion of methylmalonyl-CoA to succinyl-CoA by transfer of the carbonyl group. It requires a cobamide coenzyme. A block in this enzymatic conversion leads to the metabolic disease, methylmalonic aciduria. EC

Top Publications

  1. Crane A, Martin L, Valle D, Ledley F. Phenotype of disease in three patients with identical mutations in methylmalonyl CoA mutase. Hum Genet. 1992;89:259-64 pubmed
    We have previously identified a mutation in the gene for methylmalonyl CoA mutase in a patient with the mut- phenotype of methylmalonic aciduria...
  2. Raff M, Crane A, Jansen R, Ledley F, Rosenblatt D. Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut0 and mut- methylmalonic aciduria by interallelic complementation. J Clin Invest. 1991;87:203-7 pubmed
    ..The methylmalonyl CoA mutase cDNA was cloned from WG1130 and found to contain a G354----A (Arg93----His) mutation...
  3. Threadgill D, Wilkmeyer M, Womack J, Ledley F. Localization of the murine methylmalonyl CoA mutase (Mut) locus on chromosome 17 by in situ hybridization. Cytogenet Cell Genet. 1990;53:112-4 pubmed
    Murine methylmalonyl CoA mutase (Mut) has been localized to chromosome 17C-D by in situ hybridization in cell line containing a 2.17 Robertsonian translocation...
  4. Lempp T, Suormala T, Siegenthaler R, Baumgartner E, Fowler B, Steinmann B, et al. Mutation and biochemical analysis of 19 probands with mut0 and 13 with mut- methylmalonic aciduria: identification of seven novel mutations. Mol Genet Metab. 2007;90:284-90 pubmed
    ..1097A>G/p.N366S; c.2081G>T/p.R694L) among 13 probands with a mut(-) defect. Our study provides evidence that the p.Y100C, p.R108H, p.N366S, p.V633G, p.R694W, p.R694L and p.M700K mutations are associated with a mut(-) phenotype. ..
  5. Kaplan P, Ficicioglu C, Mazur A, Palmieri M, Berry G. Liver transplantation is not curative for methylmalonic acidopathy caused by methylmalonyl-CoA mutase deficiency. Mol Genet Metab. 2006;88:322-6 pubmed
    ..Liver replacement is not a cure for methylmalonic acidopathy. ..
  6. Acquaviva C, Benoist J, Pereira S, Callebaut I, Koskas T, Porquet D, et al. Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(o) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene. Hum Mutat. 2005;25:167-76 pubmed
    ..shermanii enzyme. In this work we update the spectrum of MCM mutations (n=84), and then discuss their prevalence and distribution throughout the coding sequence in relation to the enzyme structure. ..
  7. Janata J, Kogekar N, Fenton W. Expression and kinetic characterization of methylmalonyl-CoA mutase from patients with the mut- phenotype: evidence for naturally occurring interallelic complementation. Hum Mol Genet. 1997;6:1457-64 pubmed
    ..This finding may reflect the natural occurrence of interallelic complementation in vivo in this cell line. ..
  8. Haydock S, Mironenko T, Ghoorahoo H, Leadlay P. The putative elaiophylin biosynthetic gene cluster in Streptomyces sp. DSM4137 is adjacent to genes encoding adenosylcobalamin-dependent methylmalonyl CoA mutase and to genes for synthesis of cobalamin. J Biotechnol. 2004;113:55-68 pubmed
    ..biosynthetic gene cluster is a 30-kbp region containing the gene for adenosylcobalamin-dependent methylmalonyl CoA mutase and also genes involved in the biosynthesis of the cobalamin cofactor...
  9. Chandler R, Zerfas P, Shanske S, Sloan J, Hoffmann V, DiMauro S, et al. Mitochondrial dysfunction in mut methylmalonic acidemia. FASEB J. 2009;23:1252-61 pubmed publisher

More Information


  1. Chandler R, Venditti C. Adenovirus-mediated gene delivery rescues a neonatal lethal murine model of mut(0) methylmalonic acidemia. Hum Gene Ther. 2008;19:53-60 pubmed
  2. Peters H, Nefedov M, Sarsero J, Pitt J, Fowler K, Gazeas S, et al. A knock-out mouse model for methylmalonic aciduria resulting in neonatal lethality. J Biol Chem. 2003;278:52909-13 pubmed
    ..This is the first mouse model that recapitulates the key phenotypic features of mut0 methylmalonic aciduria. ..
  3. Nyhan W, Gargus J, Boyle K, Selby R, Koch R. Progressive neurologic disability in methylmalonic acidemia despite transplantation of the liver. Eur J Pediatr. 2002;161:377-9 pubmed
    ..experience with a 24-year-old patient treated with hepatic transplantation indicates that this procedure does not prevent progressive renal failure and neurologic dysfunction. ..
  4. Wilkemeyer M, Crane A, Ledley F. Primary structure and activity of mouse methylmalonyl-CoA mutase. Biochem J. 1990;271:449-55 pubmed
    ..These results establish that mouse MCM is homologous to human MCM in structure and function and provides a basis for using the mouse as a model for studying this enzyme and its deficiency state. ..
  5. Wilkemeyer M, Andrews E, Ledley F. Genomic structure of murine methylmalonyl-CoA mutase: evidence for genetic and epigenetic mechanisms determining enzyme activity. Biochem J. 1993;296 ( Pt 3):663-70 pubmed
    ..These results suggest that, although there may be regulation of MCM activity at the level of mRNA, the significance of genetic regulation is unclear owning to the presence of epigenetic regulation of holoenzyme formation. ..
  6. Crane A, Ledley F. Clustering of mutations in methylmalonyl CoA mutase associated with mut- methylmalonic acidemia. Am J Hum Genet. 1994;55:42-50 pubmed
    Mutations have been described in human methylmalonyl CoA mutase (MCM) that exhibit partial defects in enzyme activity, including cobalamin-dependent (i.e., mut-) or interallelic complementation...
  7. Worgan L, Niles K, Tirone J, Hofmann A, Verner A, Sammak A, et al. Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype. Hum Mutat. 2006;27:31-43 pubmed
    ..class) results from mutations in the nuclear gene MUT, which codes for the mitochondrial enzyme methylmalonyl CoA mutase (MCM)...
  8. Martínez M, Rincon A, Desviat L, Merinero B, Ugarte M, Perez B. Genetic analysis of three genes causing isolated methylmalonic acidemia: identification of 21 novel allelic variants. Mol Genet Metab. 2005;84:317-25 pubmed
    ..1846C>T (p.R616C), and c.1850T>G (p.L617R) are probably mut0. In the MMAA patients analyzed, frameshift mutations are prevalent. We have explored the genotype-phenotype correlation for this clinically heterogeneous disease. ..
  9. Fuchshuber A, Mucha B, Baumgartner E, Vollmer M, Hildebrandt F. mut0 methylmalonic acidemia: eleven novel mutations of the methylmalonyl CoA mutase including a deletion-insertion mutation. Hum Mutat. 2000;16:179 pubmed
    ..The position in relation to different functional domains in MCM allow for an interpretation of the identified mutations. Hum Mutat 16:179, 2000. ..
  10. Chandler R, Aswani V, Tsai M, Falk M, Wehrli N, Stabler S, et al. Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolism. Mol Genet Metab. 2006;89:64-73 pubmed
    ..elegans RNAi and deletion mutants. ..
  11. Fenton W, Hack A, Kraus J, Rosenberg L. Immunochemical studies of fibroblasts from patients with methylmalonyl-CoA mutase apoenzyme deficiency: detection of a mutation interfering with mitochondrial import. Proc Natl Acad Sci U S A. 1987;84:1421-4 pubmed
  12. Chandler R, Tsai M, Dorko K, Sloan J, Korson M, Freeman R, et al. Adenoviral-mediated correction of methylmalonyl-CoA mutase deficiency in murine fibroblasts and human hepatocytes. BMC Med Genet. 2007;8:24 pubmed
    ..Primary hepatocytes from a liver that was unsuitable for transplantation provided an important resource for these studies. ..
  13. Chandler R, Sloan J, Fu H, Tsai M, Stabler S, Allen R, et al. Metabolic phenotype of methylmalonic acidemia in mice and humans: the role of skeletal muscle. BMC Med Genet. 2007;8:64 pubmed
    ..This mouse model will be useful for further investigations exploring disease mechanisms and therapeutic interventions in methylmalonic acidemia, a devastating disorder of intermediary metabolism. ..
  14. Ledley F, Rosenblatt D. Mutations in mut methylmalonic acidemia: clinical and enzymatic correlations. Hum Mutat. 1997;9:1-6 pubmed
    Mut methylmalonic acidemia is caused by mutations in the MUT locus encoding the enzyme methylmalonyl CoA mutase. Genotypic and phenotypic variability in this disease has been studied extensively by biochemical and somatic cell genetic ..
  15. Kasahara M, Horikawa R, Tagawa M, Uemoto S, Yokoyama S, Shibata Y, et al. Current role of liver transplantation for methylmalonic acidemia: a review of the literature. Pediatr Transplant. 2006;10:943-7 pubmed
    ..7%) had postoperative neurological disability. Continuing metabolic damage to the kidney and brain may occur even after successful LT. Further evaluation is required to determine the long-term suitability of this treatment modality. ..
  16. Hörster F, Baumgartner M, Viardot C, Suormala T, Burgard P, Fowler B, et al. Long-term outcome in methylmalonic acidurias is influenced by the underlying defect (mut0, mut-, cblA, cblB). Pediatr Res. 2007;62:225-30 pubmed
    ..In addition, long-term outcome was dependent on the age cohort and cobalamin responsiveness. ..
  17. Devi A, Naushad S. Targeted exome sequencing for the identification of complementation groups in methylmalonic aciduria: A south Indian experience. Clin Biochem. 2017;50:68-72 pubmed publisher
    ..Both B12-responsive and non-responsive patients were diagnosed. In biochemically diagnosed patients, targeted exome sequencing is cost effective to identify different MMA causing mutations and facilitate genetic counseling. ..
  18. Liu Y, DING Y, Li X, Wang H, Song J, Ye J, et al. [Acute brainstem encephalitis and myelitis in a girl with isolated methylmalonic aciduria due to MUT gene defect]. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17:1103-6 pubmed
    b>Methylmalonyl CoA mutase deficiency due to MUT gene defect has been known as the main cause of isolated methylmalonic acidemia in Mainland China...
  19. Nham S, Wilkemeyer M, Ledley F. Structure of the human methylmalonyl-CoA mutase (MUT) locus. Genomics. 1990;8:710-6 pubmed
    ..These studies describe the structure of the MUTlocus and provide a foundation for characterization of mutations in mut methylmalonic acidemia. ..
  20. Gailus S, Suormala T, Malerczyk Aktas A, Toliat M, Wittkampf T, Stucki M, et al. A novel mutation in LMBRD1 causes the cblF defect of vitamin B(12) metabolism in a Turkish patient. J Inherit Metab Dis. 2010;33:17-24 pubmed publisher
    ..This case adds to the spectrum of clinical presentations and mutations of this rare disorder of lysosomal transport. ..
  21. Biancheri R, Cerone R, Schiaffino M, Caruso U, Veneselli E, Perrone M, et al. Cobalamin (Cbl) C/D deficiency: clinical, neurophysiological and neuroradiologic findings in 14 cases. Neuropediatrics. 2001;32:14-22 pubmed
  22. Aldor I, Kim S, Prather K, Keasling J. Metabolic engineering of a novel propionate-independent pathway for the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in recombinant Salmonella enterica serovar typhimurium. Appl Environ Microbiol. 2002;68:3848-54 pubmed
    ..It was possible to vary the average HV fraction in the copolymer by adjusting the arabinose or cyanocobalamin (precursor of coenzyme B12) concentration in the medium. ..
  23. Zerbe Burkhardt K, Ratnatilleke A, Philippon N, Birch A, Leiser A, Vrijbloed J, et al. Cloning, sequencing, expression, and insertional inactivation of the gene for the large subunit of the coenzyme B12-dependent isobutyryl-CoA mutase from Streptomyces cinnamonensis. J Biol Chem. 1998;273:6508-17 pubmed
    ..After purification, this small subunit showed no ICM activity but gave active enzyme when recombined with coenzyme B12 and IcmA or His6-IcmA...
  24. Cavicchi C, Donati M, Pasquini E, Poggi G, Dionisi Vici C, Parini R, et al. Mutational spectrum in ten Italian patients affected by methylmalonyl-CoA mutase deficiency. J Inherit Metab Dis. 2005;28:1175-8 pubmed
    ..Arg31X, p.Glu 451X), one splicing defect (c.2125-1G >A), one small deletion (c.1758-1759delA) and nine previously described mutations identified in 10 unrelated Italian patients affected by mut MMA. ..
  25. Al Hasani K, Simpfendorfer K, Wardan H, Vadolas J, Zaibak F, Villain R, et al. Development of a novel bacterial artificial chromosome cloning system for functional studies. Plasmid. 2003;49:184-7 pubmed
    ..Clones from any eukaryotic genomic library harboured in this vector can be transferred from bacteria directly to eukaryotic cells for functional analysis. ..
  26. Roy I, Leadlay P. Physical map location of the new Escherichia coli gene sbm. J Bacteriol. 1992;174:5763-4 pubmed
  27. Korotkova N, Chistoserdova L, Kuksa V, Lidstrom M. Glyoxylate regeneration pathway in the methylotroph Methylobacterium extorquens AM1. J Bacteriol. 2002;184:1750-8 pubmed
    ..A new scheme for the pathway is proposed based on these data. ..
  28. Hubbard P, Padovani D, Labunska T, Mahlstedt S, Banerjee R, Drennan C. Crystal structure and mutagenesis of the metallochaperone MeaB: insight into the causes of methylmalonic aciduria. J Biol Chem. 2007;282:31308-16 pubmed
  29. Mahfoud A, Dominguez C, Pérez A, Rizzo C, Merinero B, Perez B. [Diagnosis and treatment of methylmalonic aciduria: a case report]. Invest Clin. 2007;48:99-105 pubmed
    ..The definitive diagnosis is important because it may allow a specific treatment and a favorable evolution to prevent the secuelae. ..
  30. Savvi S, Warner D, Kana B, McKinney J, Mizrahi V, Dawes S. Functional characterization of a vitamin B12-dependent methylmalonyl pathway in Mycobacterium tuberculosis: implications for propionate metabolism during growth on fatty acids. J Bacteriol. 2008;190:3886-95 pubmed publisher
    ..tuberculosis in mice. ..
  31. Botella L, Lindley N, Eggeling L. Formation and metabolism of methylmalonyl coenzyme A in Corynebacterium glutamicum. J Bacteriol. 2009;191:2899-901 pubmed publisher
    ..The physiological context of the mutase present in members of the suborder Corynebacterineae is discussed. ..
  32. Li X, Chung L, Paneth P, Morokuma K. DFT and ONIOM(DFT:MM) studies on Co-C bond cleavage and hydrogen transfer in B12-dependent methylmalonyl-CoA mutase. Stepwise or concerted mechanism?. J Am Chem Soc. 2009;131:5115-25 pubmed publisher
    ..Key factors and residues in promoting the enzymatic reaction rate have been discussed in detail. ..
  33. Ludwig M, Matthews R. Structure-based perspectives on B12-dependent enzymes. Annu Rev Biochem. 1997;66:269-313 pubmed
    ..The intermediate radical species generated in catalysis are sequestered in the relatively hydrophilic core of an alpha/beta barrel domain of the mutase. ..
  34. Keeratichamroen S, Cairns J, Sawangareetrakul P, Liammongkolkul S, Champattanachai V, Srisomsap C, et al. Novel mutations found in two genes of thai patients with isolated methylmalonic acidemia. Biochem Genet. 2007;45:421-30 pubmed
    ..1671A --> G), and p.V671I (c.2087G --> A). The new MMAB mutation, p.E152X (c.454G --> T), was found to be homozygous in one cblB patient and heterozygous in the other patient, who also had four intron polymorphisms in this gene. ..
  35. Miyamoto E, Watanabe F, Yamaji R, Inui H, Sato K, Nakano Y. Purification and characterization of methylmalonyl-CoA mutase from a methanol-utilizing bacterium, Methylobacterium extorquens NR-1. J Nutr Sci Vitaminol (Tokyo). 2002;48:242-6 pubmed
    ..extorquens NR-1 enzyme showed no significant homology to those of the enzyme from other species. Some enzymological properties of the M. extorquens NR-1 enzyme were studied. ..
  36. Valentin H, Dennis D. Metabolic pathway for poly(3-hydroxybutyrate-co-3-hydroxyvalerate) formation in Nocardia corallina: inactivation of mutB by chromosomal integration of a kanamycin resistance gene. Appl Environ Microbiol. 1996;62:372-9 pubmed
    ..Therefore, this study provides strong evidence that the majority of 3HV units in poly(3HB-co-3HV) accumulated by N. corallina are synthesized via the methylmalonyl-CoA pathway. ..
  37. Paizs C, Diemer T, Retey J. The putative coenzyme B12-dependent methylmalonyl-CoA mutase from potatoes is a phosphatase. Bioorg Chem. 2008;36:261-4 pubmed publisher
    ..Examination of the reaction product by 1H, 31P NMR and mass spectrometry revealed that it was methylmalonyl-3'-dephospho-CoA. The phosphatase enzyme needs neither coenzyme B12 nor S-adenosylmethionine as a cofactor. ..
  38. Taoka S, Padmakumar R, Grissom C, Banerjee R. Magnetic field effects on coenzyme B12-dependent enzymes: validation of ethanolamine ammonia lyase results and extension to human methylmalonyl CoA mutase. Bioelectromagnetics. 1997;18:506-13 pubmed
    ..Our studies suggest that putative magnetic field effects on physiological processes are not likely to be mediated by methylmalonyl-CoA mutase. ..
  39. Ballesteros C, Garrido J, Vicente J, Romero B, Galindo R, Minguijon E, et al. First data on Eurasian wild boar response to oral immunization with BCG and challenge with a Mycobacterium bovis field strain. Vaccine. 2009;27:6662-8 pubmed publisher
    ..More studies on vaccine efficacy, delivery, and safety will be needed to confirm if oral vaccination with BCG could be used in bTB control programs for reducing M. bovis infection and clinical disease in wild boar. ..
  40. Sakamoto O, Ohura T, Matsubara Y, Takayanagi M, Tsuchiya S. Mutation and haplotype analyses of the MUT gene in Japanese patients with methylmalonic acidemia. J Hum Genet. 2007;52:48-55 pubmed
    ..This finding - that a limited number of mutations account for most of the mutations in Japanese mut MMA patients - is in contrast with results of a previous study in Caucasian patients. ..
  41. Riedel B, Fiskerstrand T, Refsum H, Ueland P. Co-ordinate variations in methylmalonyl-CoA mutase and methionine synthase, and the cobalamin cofactors in human glioma cells during nitrous oxide exposure and the subsequent recovery phase. Biochem J. 1999;341 ( Pt 1):133-8 pubmed
  42. Kennedy S, McConnell S, Anderson H, Kennedy D, Young P, Blanchflower W. Histopathologic and ultrastructural alterations of white liver disease in sheep experimentally depleted of cobalt. Vet Pathol. 1997;34:575-84 pubmed
    ..Reduced activities of the vitamin B12-dependent enzymes, methylmalonyl CoA mutase and methionine synthase, and lipid peroxidation are of likely pathogenetic importance in the development ..
  43. Froese D, Kopec J, Fitzpatrick F, Schuller M, McCorvie T, Chalk R, et al. Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking. J Biol Chem. 2015;290:29167-77 pubmed publisher
  44. Pare G, Chasman D, Parker A, Zee R, Malarstig A, Seedorf U, et al. Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women's Genome Health Study. Circ Cardiovasc Genet. 2009;2:142-50 pubmed publisher
    ..These associations offer new insight into the biochemical pathways involved in homocysteine metabolism and provide opportunities to better delineate the role of homocysteine in health and disease. ..
  45. Qureshi A, Crane A, Matiaszuk N, Rezvani I, Ledley F, Rosenblatt D. Cloning and expression of mutations demonstrating intragenic complementation in mut0 methylmalonic aciduria. J Clin Invest. 1994;93:1812-9 pubmed
    The mut0 mutation resulting in methylmalonyl CoA mutase (MCM) apoenzyme deficiency and methylmalonic aciduria is characterized by undetectable enzyme activity in cell extracts and low incorporation of propionate into cultured cells which ..
  46. Tanpaiboon P. Methylmalonic acidemia (MMA). Mol Genet Metab. 2005;85:2-6 pubmed
  47. Berger I, Shaag A, Anikster Y, Baumgartner E, Bar Meir M, Joseph A, et al. Mutation analysis of the MCM gene in Israeli patients with mut(0) disease. Mol Genet Metab. 2001;73:107-10 pubmed
    ..Nonetheless, delayed onset was not associated with better neurological outcome and prolonged survival. The large number of undiagnosed dead sibs in most families suggests that the disease is largely underdiagnosed in this region. ..
  48. Mücher G, Becker J, Knapp M, Buttner R, Moser M, Rudnik Schoneborn S, et al. Fine mapping of the autosomal recessive polycystic kidney disease locus (PKHD1) and the genes MUT, RDS, CSNK2 beta, and GSTA1 at 6p21.1-p12. Genomics. 1998;48:40-5 pubmed
    ..These genetic data, combined with our YAC-based physical map of the 6p21-p12 region, will facilitate efforts to positionally clone the PKHD1 gene. ..
  49. Ledley F, Lumetta M, Nguyen P, Kolhouse J, Allen R. Molecular cloning of L-methylmalonyl-CoA mutase: gene transfer and analysis of mut cell lines. Proc Natl Acad Sci U S A. 1988;85:3518-21 pubmed
  50. Kolhouse J, Utley C, Allen R. Isolation and characterization of methylmalonyl-CoA mutase from human placenta. J Biol Chem. 1980;255:2708-12 pubmed
    ..2 M dithiothreitol, or both, suggesting the possibility that cobalamin may be covalently attached to the purified enzyme. Both precipitating antibodies and antibodies that inhibit enzyme activity have been raised in a chicken. ..
  51. Selhub J, Morris M, Jacques P, Rosenberg I. Folate-vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency. Am J Clin Nutr. 2009;89:702S-6S pubmed publisher
  52. Horster F, Garbade S, Zwickler T, Aydin H, Bodamer O, Burlina A, et al. Prediction of outcome in isolated methylmalonic acidurias: combined use of clinical and biochemical parameters. J Inherit Metab Dis. 2009;32:630 pubmed publisher
    ..The prognosis is still unfavourable in patients with neonatal metabolic crises and non-responsiveness to cobalamin, in particular mut(0) patients. ..
  53. Haller T, Buckel T, Retey J, Gerlt J. Discovering new enzymes and metabolic pathways: conversion of succinate to propionate by Escherichia coli. Biochemistry. 2000;39:4622-9 pubmed
    ..that YgfG is methylmalonyl CoA decarboxylase, YgfH is propionyl CoA:succinate CoA transferase, and Sbm is methylmalonyl CoA mutase. These reactions are sufficient to form a metabolic cycle by which E...
  54. Miranda N, Daublain P, Horner J, Newcomb M. Carboxylate-substituted radicals from phenylselenide derivatives. Designs on models for coenzyme B12-dependent enzyme-catalyzed rearrangements. J Am Chem Soc. 2003;125:5260-1 pubmed
  55. Bandarian V. Delivery of tailor-made cobalamin to methylmalonyl-CoA mutase. Nat Chem Biol. 2008;4:158-9 pubmed publisher
  56. Miyamoto E, Tanioka Y, Yukino T, Hayashi M, Watanabe F, Nakano Y. Occurrence of 5'-deoxyadenosylcobalamin and its physiological function as the coenzyme of methylmalonyl-CoA mutase in a marine eukaryotic microorganism, Schizochytrium limacinum SR21. J Nutr Sci Vitaminol (Tokyo). 2007;53:471-5 pubmed
    ..4.99.2) involved in amino acid and odd-chain fatty acid metabolism was found in the cell homogenate of S. limacinum SR21. The enzyme was purified to homogeneity and characterized. ..
  57. Vlasie M, Banerjee R. Tyrosine 89 accelerates Co-carbon bond homolysis in methylmalonyl-CoA mutase. J Am Chem Soc. 2003;125:5431-5 pubmed
    ..Together, these results are consistent with homolysis becoming completely rate determining in the forward direction in the two mutants and points to the role of Y89 as a molecular wedge in accelerating Co-carbon bond cleavage. ..
  58. Perez B, Rincon A, Jorge Finnigan A, Richard E, Merinero B, Ugarte M, et al. Pseudoexon exclusion by antisense therapy in methylmalonic aciduria (MMAuria). Hum Mutat. 2009;30:1676-82 pubmed publisher
  59. Freindorf M, Kozlowski P. A combined density functional theory and molecular mechanics study of the relationship between the structure of coenzyme B12 and its binding to methylmalonyl-CoA mutase. J Am Chem Soc. 2004;126:1928-9 pubmed
    ..The controlling of this distance is important to inhibit abiological site reaction involving heterolysis of the Co-C bond but is not important for biologically relevant Co-C bond homolysis. ..
  60. Crane A, Jansen R, Andrews E, Ledley F. Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut- methylmalonic aciduria. J Clin Invest. 1992;89:385-91 pubmed
    Distinct genotypic and phenotypic forms of methylmalonyl CoA mutase (MCM) apoenzyme deficiency can be delineated by biochemical analysis of mutant fibroblasts...
  61. Roy I. The masked cysteine residues in methylmalonyl-CoA mutase from Propionibacterium shermanii are essential for catalytic activity. FEBS Lett. 1996;394:126-8 pubmed
    ..These two masked cysteine residues have been changed to an alanine, individually. Both the mutants, C535alphaA and C517betaA, were inactive. This shows that both these residues are essential for catalytic activity. ..
  62. Zhang H, Boghigian B, Pfeifer B. Investigating the role of native propionyl-CoA and methylmalonyl-CoA metabolism on heterologous polyketide production in Escherichia coli. Biotechnol Bioeng. 2010;105:567-73 pubmed publisher
    ..Lastly, the effect of the ygfH deletion was tested in batch bioreactor cultures in which 6dEB titers improved from 206 to 527 mg/L. ..
  63. Mo S, Ban Y, Park J, Yoo Y, Yoon Y. Enhanced FK506 production in Streptomyces clavuligerus CKD1119 by engineering the supply of methylmalonyl-CoA precursor. J Ind Microbiol Biotechnol. 2009;36:1473-82 pubmed publisher
    ..clavuligerus CKD1119. ..
  64. Kozlowski P, Kamachi T, Kumar M, Nakayama T, Yoshizawa K. Theoretical analysis of the diradical nature of adenosylcobalamin cofactor-tyrosine complex in B12-dependent mutases: inspiring PCET-driven enzymatic catalysis. J Phys Chem B. 2010;114:5928-39 pubmed publisher
    ..e., [AdoCbl](*-)), rather than its neutral analogue, thus providing an efficient mode of cleavage that can help in understanding the origin of the catalytic effect in such enzymes. ..
  65. Ballhausen D, Mittaz L, Boulat O, Bonafe L, Braissant O. Evidence for catabolic pathway of propionate metabolism in CNS: expression pattern of methylmalonyl-CoA mutase and propionyl-CoA carboxylase alpha-subunit in developing and adult rat brain. Neuroscience. 2009;164:578-87 pubmed publisher
    ..In rat embryos (E15.5 and E18.5), MCM and PCC show a much higher expression level in the entire CNS than in the liver, suggesting a different, but important function of this pathway during brain development. ..
  66. Padovani D, Banerjee R. A rotary mechanism for coenzyme B(12) synthesis by adenosyltransferase. Biochemistry. 2009;48:5350-7 pubmed publisher
  67. Drennan C, Huang S, Drummond J, Matthews R, Lidwig M. How a protein binds B12: A 3.0 A X-ray structure of B12-binding domains of methionine synthase. Science. 1994;266:1669-74 pubmed
    ..Thus the cobalt ligand, His759, and the neighboring residues Asp757 and Ser810, may form a catalytic quartet, Co-His-Asp-Ser, that modulates the reactivity of the B12 prosthetic group in methionine synthase. ..
  68. Vlasie M, Chowdhury S, Banerjee R. Importance of the histidine ligand to coenzyme B12 in the reaction catalyzed by methylmalonyl-CoA mutase. J Biol Chem. 2002;277:18523-7 pubmed
  69. Winston G, Jaiser S. Copper deficiency myelopathy and subacute combined degeneration of the cord - why is the phenotype so similar?. Med Hypotheses. 2008;71:229-36 pubmed publisher
    ..If it were confirmed, the hypothesis would not only provide a plausible explanation for the phenotypic similarity between CDM and SCD, but might also open up further therapeutic options such as methionine and betaine supplementation. ..
  70. Champattanachai V, Ketudat Cairns J, Shotelersuk V, Keeratichamroen S, Sawangareetrakul P, Srisomsap C, et al. Novel mutations in a Thai patient with methylmalonic acidemia. Mol Genet Metab. 2003;79:300-2 pubmed
    ..The proband was also heterozygous for the polymorphism, A499T, which did not affect the activity of recombinant MCM. ..
  71. Maeda Y, Ito T, Suzuki A, Kurono Y, Ueta A, Yokoi K, et al. Simultaneous quantification of acylcarnitine isomers containing dicarboxylic acylcarnitines in human serum and urine by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2007;21:799-806 pubmed
    ..The described HPLC/MS/MS method could separate most acylcarnitine isomers and quantify them, potentially allowing detailed diagnoses and follow-up treatment for those diseases. ..
  72. Kozlowski P, Kamachi T, Toraya T, Yoshizawa K. Does Cob(II)alamin act as a conductor in coenzyme B12 dependent mutases?. Angew Chem Int Ed Engl. 2007;46:980-3 pubmed
  73. Zoghbi H, O Brien W, Ledley F. Linkage relationships of the human methylmalonyl CoA mutase to the HLA and D6S4 loci on chromosome 6. Genomics. 1988;3:396-8 pubmed
    The human methylmalonyl CoA mutase (MCM) cDNA has been used to localize the MUT locus on the short arm of chromosome 6 proximal to the glyoxalase locus in 6p deletion cell lines...
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    ..We speculate that we have identified a component of a transporter or an accessory protein that is involved in the translocation of vitamin B(12) into mitochondria. ..
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    ..The strategy of using the final enzyme in an assimilation pathway for tailoring a cofactor and delivering it to a dependent enzyme may be general for cofactor trafficking...
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    ..This study revealed partial MUT gene mutation spectrum in Chinese patients with isolated MMA. The patients carrying MUT mutations often had early-onset disease, and most of them were VitB(12)- non-responsive. ..
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    ..06 cM distal to H-2, between Pgk-2 and Ce-2. The relative order of syntenic probes flanking H-2 on mouse chromosome 17 and HLA on human chromosome 6 is shown to be different. ..
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    ..Downstream of, and oriented towards bhbA, was identified a member of the GNTR class of transcriptional regulator-encoding genes. It is not yet known whether this regulatory protein is directly involved in modulation of bhbA expression...
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    ..The thermodynamic dis-equilibrium of the combined reactions of the propionyl-CoA pathway explains the effectiveness of anaplerosis from propionyl-CoA precursors such as heptanoate. ..
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    ..These studies serve to emphasize the fine control exerted by Y243 in the vicinity of the substrate to minimize radical extinction in side reactions. ..