MECR

{{Short description|Protein-coding gene in the species Homo sapiens}}

Trans-2-enoyl-CoA reductase, mitochondrial is an enzyme that in humans is encoded by the MECR gene.{{cite journal | vauthors = Masuda N, Yasumo H, Furusawa T, Tsukamoto T, Sadano H, Osumi T | title = Nuclear receptor binding factor-1 (NRBF-1), a protein interacting with a wide spectrum of nuclear hormone receptors | journal = Gene | volume = 221 | issue = 2 | pages = 225–33 | date = October 1998 | pmid = 9795230 | doi = 10.1016/S0378-1119(98)00461-2 }}{{cite journal | vauthors = Miinalainen IJ, Chen ZJ, Torkko JM, Pirilä PL, Sormunen RT, Bergmann U, Qin YM, Hiltunen JK | title = Characterization of 2-enoyl thioester reductase from mammals. An ortholog of YBR026p/MRF1'p of the yeast mitochondrial fatty acid synthesis type II | journal = The Journal of Biological Chemistry | volume = 278 | issue = 22 | pages = 20154–61 | date = May 2003 | pmid = 12654921 | doi = 10.1074/jbc.M302851200 | doi-access = free }}{{cite web | title = Entrez Gene: MECR mitochondrial trans-2-enoyl-CoA reductase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51102}}

Structure

The MECR gene is located on the 1st chromosome, with its specific location being 1p35.3. The gene contains 15 exons. MECR encodes a 21.2 kDa protein that is composed of 189 amino acids; 10 peptides have been observed through mass spectrometry data.]{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}{{cite web | url = http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=QQ5SYU3 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = Mitochondrial trans-2-enoyl-CoA reductase }}{{Dead link|date=October 2022 |bot=InternetArchiveBot |fix-attempted=yes }}

Function

File:Mitochondrial fatty acid synthesis (mtFAS) pathway.svg

The protein encoded by MECR is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis (mtFAS).{{cite journal |vauthors=Nowinski SM, Van Vranken JG, Dove KK, Rutter J |date=October 2018 |title=Impact of Mitochondrial Fatty Acid Synthesis on Mitochondrial Biogenesis |journal=Current Biology |volume=28 |issue=20 |pages=R1212–R1219 |bibcode=2018CBio...28R1212N |doi=10.1016/j.cub.2018.08.022 |pmc=6258005 |pmid=30352195}} MECR reduces trans-2-enoyl-ACP to acyl-ACP using NADPH as a reducing agent. The resulting saturated acyl-ACP can then re-enter the mtFAS cycle for further chain elongation.{{Cite journal |last1=Nowinski |first1=Sara M |last2=Solmonson |first2=Ashley |last3=Rusin |first3=Scott F |last4=Maschek |first4=J Alan |last5=Bensard |first5=Claire L |last6=Fogarty |first6=Sarah |last7=Jeong |first7=Mi-Young |last8=Lettlova |first8=Sandra |last9=Berg |first9=Jordan A |last10=Morgan |first10=Jeffrey T |last11=Ouyang |first11=Yeyun |last12=Naylor |first12=Bradley C |last13=Paulo |first13=Joao A |last14=Funai |first14=Katsuhiko |last15=Cox |first15=James E |date=2020-08-17 |title=Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria |journal=eLife |language=en |volume=9 |doi=10.7554/eLife.58041 |doi-access=free |issn=2050-084X |pmc=7470841 |pmid=32804083}} The reaction can be summarized by the following equation:

trans-2-enoyl-ACP + NADPH + H⁺ → Acyl-ACP + NADP⁺

The mtFAS pathway is essential for producing octanoyl-ACP that is used to synthesize lipoic acid, which is essential for aerobic metabolism.

A Purkinje cell specific knock out of the Mecr gene in mice leads to neurodegeneration.{{cite journal | vauthors = Nair RR, Koivisto H, Jokivarsi K, Miinalainen IJ, Autio KJ, Manninen A, Poutiainen P, Tanila H, Hiltunen JK, Kastaniotis AJ | title = Impaired Mitochondrial Fatty Acid Synthesis Leads to Neurodegeneration in Mice | journal = The Journal of Neuroscience | volume = 38 | issue = 45 | pages = 9781–9800 | date = November 2018 | pmid = 30266742 | pmc = 6595986 | doi = 10.1523/JNEUROSCI.3514-17.2018 }}

Clinical significance

Genetic mutations to MECR have been suggested to cause MEPAN Syndrome, a neurometabolic disorder in humans that involves disruptions in the pathway involved in mitochondrial fatty acid synthesis (mtFAS). MEPAN patients were found to harbor recessive mutations in MECR, and typically present with childhood-onset dystonia, optic atrophy, and basal ganglia signal abnormalities on MRI.{{cite journal | vauthors = Heimer G, Kerätär JM, Riley LG, Balasubramaniam S, Eyal E, Pietikäinen LP, Hiltunen JK, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance MA, Shalva N, Veber A, Tzadok M, Nissenkorn A, Tonduti D, Renaldo F, Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Hoffmann C, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B, Hayflick SJ | title = MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder | journal = American Journal of Human Genetics | volume = 99 | issue = 6 | pages = 1229–1244 | date = December 2016 | pmid = 27817865 | pmc = 5142118 | doi = 10.1016/j.ajhg.2016.09.021 }}

MECR

Structure

Function

Clinical significance

See also

References

Further reading