Encyclopedia
Methylmalonyl-CoA mutase
- genes
1. Normal Function
The MMUT gene provides instructions for making an enzyme called methylmalonyl CoA mutase. This enzyme is active in mitochondria, which are specialized structures inside cells that serve as energy-producing centers.
Methylmalonyl CoA mutase is responsible for a particular step in the breakdown of several protein building blocks (amino acids), specifically isoleucine, methionine, threonine, and valine. The enzyme also helps break down certain types of fats (lipids) and cholesterol. First, several chemical reactions convert the amino acids, lipids, or cholesterol to a molecule called methylmalonyl CoA. Then, working with a compound called adenosylcobalamin (AdoCbl), which is a form of vitamin B12, methylmalonyl CoA mutase converts methylmalonyl CoA to a compound called succinyl-CoA. Other enzymes break down succinyl-CoA into molecules that are later used for energy.
2. Health Conditions Related to Genetic Changes
2.1. Methylmalonic acidemia
More than 200 mutations in the MMUT gene have been identified in people with methylmalonic acidemia, a condition characterized by feeding difficulties, developmental delay, and long-term health problems. These genetic changes prevent the production of functional methylmalonyl CoA mutase or reduce the activity of the enzyme. As a result, certain proteins and lipids are not broken down properly. This defect allows methylmalonyl CoA and other toxic compounds to build up in the body's organs and tissues, causing the signs and symptoms of methylmalonic acidemia.
Mutations that prevent the production of any functional methylmalonyl CoA mutase lead to a form of methylmalonic acidemia designated mut0. Mut0 is the most severe form of this disorder and has the poorest outcome. Mutations that alter the structure of the enzyme but do not completely eliminate its activity lead to a form of the condition designated mut-. The mut- form is typically less severe, with more variable symptoms than the mut0 form.
3. Other Names for This Gene
- MCM
- methylalonyl-CoA mutase
- methylamlony-CoA isomerase
- methylmalonyl CoA mutase
- methylmalonyl Coenzyme A mutase
- methylmalonyl Coenzyme A mutase precursor
- MUT
- MUTA_HUMAN
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/mmut
References
- Acquaviva C, Benoist JF, Pereira S, Callebaut I, Koskas T, Porquet D, Elion J.Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 Europeanpatients affected by mut(o) and mut- forms of methylmalonic acidemia:identification of 29 novel mutations in the MUT gene. Hum Mutat. 2005Feb;25(2):167-76. Citation on PubMed
- Benoist JF, Acquaviva C, Callebaut I, Guffon N, Ogier de Baulny H, Mornon JP, Porquet D, Elion J. Molecular and structural analysis of two novel mutations in apatient with mut(-) methylmalonyl-CoA deficiency. Mol Genet Metab. 2001Feb;72(2):181-4. Citation on PubMed
- Chandler RJ, Venditti CP. Genetic and genomic systems to study methylmalonicacidemia. Mol Genet Metab. 2005 Sep-Oct;86(1-2):34-43. Epub 2005 Sep 22. Review. Citation on PubMed or Free article on PubMed Central
- Fuchshuber A, Mucha B, Baumgartner ER, Vollmer M, Hildebrandt F. mut0methylmalonic acidemia: eleven novel mutations of the methylmalonyl CoA mutaseincluding a deletion-insertion mutation. Hum Mutat. 2000 Aug;16(2):179. Citation on PubMed
- 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. Citation on PubMed
- 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/ Citation on PubMed
- Peters HL, Nefedov M, Lee LW, Abdenur JE, Chamoles NA, Kahler SG, Ioannou PA. Molecular studies in mutase-deficient (MUT) methylmalonic aciduria:identification of five novel mutations. Hum Mutat. 2002 Nov;20(5):406. Citation on PubMed
- Worgan LC, Niles K, Tirone JC, Hofmann A, Verner A, Sammak A, Kucic T, Lepage P, Rosenblatt DS. Spectrum of mutations in mut methylmalonic acidemia andidentification of a common Hispanic mutation and haplotype. Hum Mutat. 2006Jan;27(1):31-43. Citation on PubMed
