Encyclopedia
metabolism of cobalamin associated A
- genes
1. Introduction
The MMAA gene provides instructions for making a protein that is involved in the formation of a compound called adenosylcobalamin (AdoCbl). AdoCbl, which is derived from vitamin B12 (also called cobalamin), is necessary for the normal function of an enzyme known as methylmalonyl CoA mutase. This enzyme helps break down certain proteins, fats (lipids), and cholesterol.
Research indicates that the MMAA protein may play a role in one of the last steps in AdoCbl formation, the transport of vitamin B12 into mitochondria (specialized structures inside cells that serve as energy-producing centers). Additional chemical reactions then convert vitamin B12 into AdoCbl. Other studies suggest that the MMAA protein may help stabilize methylmalonyl CoA mutase and protect the enzyme from being turned off (inactivated).
2. Health Conditions Related to Genetic Changes
2.1. Methylmalonic acidemia
More than 25 mutations in the MMAA gene have been found to cause methylmalonic acidemia, a condition characterized by feeding difficulties, developmental delay, and long term health problems. Some of these mutations add, delete, or duplicate a small amount of genetic material in the gene. Other mutations change a single protein building block (amino acid) used to make the MMAA protein. These mutations can lead to the production of an unstable MMAA protein or an abnormally small, nonfunctional version of the protein. It is unclear how the abnormal MMAA protein leads to the serious medical problems associated with methylmalonic acidemia. Studies suggest that without the activity of this protein, AdoCbl may not be made properly. A lack of AdoCbl impairs the function of methylmalonyl CoA mutase, which results in the incomplete break down of certain proteins and lipids. This defect allows toxic compounds to build up in the body's organs and tissues. Research suggests that a lack of AdoCbl leading to impaired methylmalonyl CoA mutase function causes the signs and symptoms of methylmalonic academia.
3. Other Names for This Gene
- cblA
- methylmalonic aciduria (cobalamin deficiency) cblA type
- methylmalonic aciduria (cobalamin deficiency) type A
- methylmalonic aciduria type A
- MMAA_HUMAN
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/mmaa
References
- Chandler RJ, Venditti CP. Genetic and genomic systems to study methylmalonicacidemia. Mol Genet Metab. 2005 Sep-Oct;86(1-2):34-43.
- Dobson CM, Wai T, Leclerc D, Wilson A, Wu X, Doré C, Hudson T, Rosenblatt DS, Gravel RA. Identification of the gene responsible for the cblA complementationgroup of vitamin B12-responsive methylmalonic acidemia based on analysis ofprokaryotic gene arrangements. Proc Natl Acad Sci U S A. 2002 Nov26;99(24):15554-9.
- Froese DS, Kochan G, Muniz JR, Wu X, Gileadi C, Ugochukwu E, Krysztofinska E, Gravel RA, Oppermann U, Yue WW. Structures of the human GTPase MMAA and vitaminB12-dependent methylmalonyl-CoA mutase and insight into their complex formation. J Biol Chem. 2010 Dec 3;285(49):38204-13. doi: 10.1074/jbc.M110.177717.
- Hörster F, Baumgartner MR, Viardot C, Suormala T, Burgard P, Fowler B,Hoffmann GF, Garbade SF, Kölker S, Baumgartner ER. Long-term outcome inmethylmalonic acidurias is influenced by the underlying defect (mut0, mut-, cblA,cblB). Pediatr Res. 2007 Aug;62(2):225-30.
- Korotkova N, Lidstrom ME. MeaB is a component of the methylmalonyl-CoA mutase complex required for protection of the enzyme from inactivation. J Biol Chem.2004 Apr 2;279(14):13652-8.
- Lerner-Ellis JP, Dobson CM, Wai T, Watkins D, Tirone JC, Leclerc D, Doré C,Lepage P, Gravel RA, Rosenblatt DS. Mutations in the MMAA gene in patients withthe cblA disorder of vitamin B12 metabolism. Hum Mutat. 2004 Dec;24(6):509-16.Erratum in: Hum Mutat. 2005 Mar;25(3):317.
- Manoli I, Sloan JL, Venditti CP. Isolated Methylmalonic Acidemia. 2005 Aug 16 [updated 2016 Dec 1]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH,Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): Universityof Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1231/
- Yang X, Sakamoto O, Matsubara Y, Kure S, Suzuki Y, Aoki Y, Suzuki Y, Sakura N,Takayanagi M, Iinuma K, Ohura T. Mutation analysis of the MMAA and MMAB genes in Japanese patients with vitamin B(12)-responsive methylmalonic acidemia:identification of a prevalent MMAA mutation. Mol Genet Metab. 2004Aug;82(4):329-33.
