View source for MMACHC

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Methylmalonic aciduria and homocystinuria type C protein''' ('''MMACHC''') is a [[protein]] that in humans is encoded by the ''MMACHC'' [[gene]].<ref name="pmid16311595">{{cite journal |vauthors=Lerner-Ellis JP, Tirone JC, Pawelek PD, Doré C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS | title = Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type | journal = Nat. Genet. | volume = 38 | issue = 1 | pages = 93–100 |date=January 2006 | pmid = 16311595 | doi = 10.1038/ng1683 | s2cid = 7688576 }}</ref>
== Function ==
The C-terminal region of the product of the MMACHC gene is similar to TonB, a bacterial protein involved in energy transduction for [[cobalamin]] uptake.<ref name="pmid16311595"/> The MMACHC gene product catalyzes the [[Nitrile|decyanation]] of [[cyanocobalamin]] as well as the [[Alkylation|dealkylation]]
of alkylcobalamins including [[methylcobalamin]] and [[adenosylcobalamin]].<ref>Luciana Hannibal, Jihoe Kim, Nicola E. Brasch, Sihe Wang, David S. Rosenblatt, Ruma Banerjee, and Donald W. Jacobsen (August 2009). [https://www.ncbi.nlm.nih.gov/pubmed/19447654 "Processing of alkylcobalamins in mammalian cells: a role for the MMACHC (cblC) gene product"]. ''Mol Genet Metab''. '''2009''' Aug; 97(4): 260–266.</ref> This function has also been attributed to [[Cyanocobalamin reductase (cyanide-eliminating)|cobalamin reductases]].<ref>Watanabe F, Nakano Y. "Purification and characterization of aquacobalamin reductases from mammals". ''Methods Enzymol''. '''1997''';281;295-305.</ref> The MMACHC gene product and cobalamin reductases enable the interconversion of cyano- and alkylcobalamins.<ref>Quadros EV, Jackson B, Hoffbrand AV, Linnell JC. "Interconversion of cobalamins in human lymphocytes in vitro and the influence of nitrous oxide on the synthesis of cobalamin coenzymes". ''Vitamin B12, Proceedings of the Third European Symposium on Vitamin B12 and Intrinsic Factor''. '''1979''';1045-1054.</ref><ref>Quadros, EV. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2809139/ "Advances in the Understanding of Cobalamin Assimilation and Metabolism"]. ''Br J Haematol''. '''2010''' Jan; 148(2): 195–204.</ref>
== Clinical significance ==
Mutations are associated with [[combined homocystinuria and methylmalonic acidemia]].<ref name="pmid16311595"/><ref name="pmid17431913">{{cite journal |vauthors=Ben-Omran TI, Wong H, Blaser S, Feigenbaum A | title = Late-onset cobalamin-C disorder: a challenging diagnosis | journal = Am. J. Med. Genet. A | volume = 143A | issue = 9 | pages = 979–84 |date=May 2007 | pmid = 17431913 | doi = 10.1002/ajmg.a.31671 | s2cid = 19791175 }}</ref><ref name="pmid16714133">{{cite journal |vauthors=Morel CF, Lerner-Ellis JP, Rosenblatt DS | title = Combined methylmalonic aciduria and homocystinuria (cblC): phenotype-genotype correlations and ethnic-specific observations | journal = Mol. Genet. Metab. | volume = 88 | issue = 4 | pages = 315–21 |date=August 2006 | pmid = 16714133 | doi = 10.1016/j.ymgme.2006.04.001 }}</ref><ref name="pmid17853453">{{cite journal |vauthors=Tsai AC, Morel CF, Scharer G, Yang M, Lerner-Ellis JP, Rosenblatt DS, Thomas JA | title = Late-onset combined homocystinuria and methylmalonic aciduria (cblC) and neuropsychiatric disturbance | journal = Am. J. Med. Genet. A | volume = 143A | issue = 20 | pages = 2430–4 |date=October 2007 | pmid = 17853453 | doi = 10.1002/ajmg.a.31932 | s2cid = 19372503 }}</ref><ref>{{Citation |last1=Sloan |first1=Jennifer L. |title=Disorders of Intracellular Cobalamin Metabolism |date=1993 |work=GeneReviews® |editor-last=Adam |editor-first=Margaret P. |url=http://www.ncbi.nlm.nih.gov/books/NBK1328/ |access-date=2024-02-24 |place=Seattle (WA) |publisher=University of Washington, Seattle |pmid=20301503 |last2=Carrillo |first2=Nuria |last3=Adams |first3=David |last4=Venditti |first4=Charles P. |editor2-last=Feldman |editor2-first=Jerry |editor3-last=Mirzaa |editor3-first=Ghayda M. |editor4-last=Pagon |editor4-first=Roberta A.}}</ref>
== References ==
{{Reflist}}
==Further reading==
{{refbegin | 2}}
*{{cite journal  |vauthors=Froese DS, Zhang J, Healy S, Gravel RA |title=Mechanism of vitamin B12-responsiveness in cblC methylmalonic aciduria with homocystinuria. |journal=Mol. Genet. Metab. |volume=98 |issue= 4 |pages= 338–43 |year= 2009 |pmid= 19700356 |doi= 10.1016/j.ymgme.2009.07.014 }}
*{{cite journal   |vauthors=Tang H, Hao H, Tang SH, etal |title=[Mutation analysis of the MMACHC gene in a pedigree with methylmalonic aciduria] |journal=Zhonghua Yi Xue Yi Chuan Xue Za Zhi |volume=26 |issue= 1 |pages= 62–5 |year= 2009 |pmid= 19199254 |doi= 10.3760/cma.j.issn.1003-9406.2009.01.014 }}
*{{cite journal   |vauthors=Profitlich LE, Kirmse B, Wasserstein MP, etal |title=High prevalence of structural heart disease in children with cblC-type methylmalonic aciduria and homocystinuria. |journal=Mol. Genet. Metab. |volume=98 |issue= 4 |pages= 344–8 |year= 2009 |pmid= 19767224 |doi= 10.1016/j.ymgme.2009.07.017 }}
*{{cite journal   |vauthors=Nogueira C, Aiello C, Cerone R, etal |title=Spectrum of MMACHC mutations in Italian and Portuguese patients with combined methylmalonic aciduria and homocystinuria, cblC type. |journal=Mol. Genet. Metab. |volume=93 |issue= 4 |pages= 475–80 |year= 2008 |pmid= 18164228 |doi= 10.1016/j.ymgme.2007.11.005 }}
*{{cite journal   |vauthors=Gregory SG, Barlow KF, McLay KE, etal |title=The DNA sequence and biological annotation of human chromosome 1. |journal=Nature |volume=441 |issue= 7091 |pages= 315–21 |year= 2006 |pmid= 16710414 |doi= 10.1038/nature04727 |bibcode=2006Natur.441..315G |s2cid=4431933 |doi-access=free }}
*{{cite journal   |vauthors=Lerner-Ellis JP, Anastasio N, Liu J, etal |title=Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations. |journal=Hum. Mutat. |volume=30 |issue= 7 |pages= 1072–81 |year= 2009 |pmid= 19370762 |doi= 10.1002/humu.21001 |s2cid=2767341 |doi-access=free }}
*{{cite journal   |vauthors=Hannibal L, Kim J, Brasch NE, etal |title=Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product. |journal=Mol. Genet. Metab. |volume=97 |issue= 4 |pages= 260–6 |year= 2009 |pmid= 19447654 |doi= 10.1016/j.ymgme.2009.04.005  |pmc=2709701 }}
*{{cite journal   |vauthors=Thauvin-Robinet C, Roze E, Couvreur G, etal |title=The adolescent and adult form of cobalamin C disease: clinical and molecular spectrum. |journal=J. Neurol. Neurosurg. Psychiatry |volume=79 |issue= 6 |pages= 725–8 |year= 2008 |pmid= 18245139 |doi= 10.1136/jnnp.2007.133025 |s2cid=23493993 }}
*{{cite journal   |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  |pmc=528928 }}
*{{cite journal   |vauthors=Kim J, Hannibal L, Gherasim C, etal |title=A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins. |journal=J. Biol. Chem. |volume=284 |issue= 48 |pages= 33418–24 |year= 2009 |pmid= 19801555 |doi= 10.1074/jbc.M109.057877  |pmc=2785186 |doi-access=free }}
*{{cite journal   |vauthors=Richard E, Jorge-Finnigan A, Garcia-Villoria J, etal |title=Genetic and cellular studies of oxidative stress in methylmalonic aciduria (MMA) cobalamin deficiency type C (cblC) with homocystinuria (MMACHC). |journal=Hum. Mutat. |volume=30 |issue= 11 |pages= 1558–66 |year= 2009 |pmid= 19760748 |doi= 10.1002/humu.21107 |s2cid=42657972 |doi-access=free }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2002 |pmid= 12477932 |doi= 10.1073/pnas.242603899  |pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
*{{cite journal   |vauthors=Loewy AD, Niles KM, Anastasio N, etal |title=Epigenetic modification of the gene for the vitamin B(12) chaperone MMACHC can result in increased tumorigenicity and methionine dependence. |journal=Mol. Genet. Metab. |volume=96 |issue= 4 |pages= 261–7 |year= 2009 |pmid= 19200761 |doi= 10.1016/j.ymgme.2008.12.011 }}
*{{cite journal  |vauthors=Kim J, Gherasim C, Banerjee R |title=Decyanation of vitamin B12 by a trafficking chaperone. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=105 |issue= 38 |pages= 14551–4 |year= 2008 |pmid= 18779575 |doi= 10.1073/pnas.0805989105  |pmc=2567227 |bibcode=2008PNAS..10514551K |doi-access=free }}
{{refend}}
==External links==
* [https://www.ncbi.nlm.nih.gov/books/NBK1328/  GeneReviews/NCBI/NIH/UW entry on Disorders of Intracellular Cobalamin Metabolism]
{{Metabolism of vitamins, coenzymes, and cofactors}}
{{gene-1-stub}}