HADHA: Difference between revisions

'''HydroxyacylTrifunctional enzyme subunit alpha, mitochondrial''' also known as '''hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit''' is a [[protein]] that in humans is encoded by the ''HADHA'' [[gene]]. TheMutations genesin of''HADHA'' thehave alphabeen andassociated betawith subunits[[Mitochondrial oftrifunctional the mitochondrialprotein deficiency|trifunctional protein aredeficiency]] locatedor adjacent to each other in the[[long-chain human genome in a head3-tohydroxyacyl-headcoenzyme orientationA dehydrogenase deficiency]].<ref name="entrez">{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/3030|title = Entrez Gene: Hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit | url = http://www.ncbi.nlm.nih.gov/gene/3030 }}</ref>

'''HADHA''' is aan 82.9 kDa protein composed of 763 amino acids.<ref name=COPaKB>]{{vcite2cite 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 = 1043-531043–53 | date = Oct 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref><ref name="url_COPaKB">{{cite web | url = http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P40939 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit | access-date = 2015-03-18 | archive-date = 2016-03-05 | archive-url = https://web.archive.org/web/20160305175422/http://heartproteome.org/copa/proteininfo.aspx?qtype=protein%20id&qvalue=p40939 | url-status = dead }}</ref>

The [[mitochondrial]] membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the alpha subunit catalyzing the [[3-hydroxyacyl-CoA dehydrogenase]] and [[enoyl-CoA hydratase]] activities. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation. <ref name="entrez"/>

This gene encodes the alpha subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial [[Beta oxidation|beta-oxidation]] of long chain fatty acids. <ref name="entrez"/> The enzyme converts medium- and long-chain 2-enoyl-CoA compounds into the following 3-ketoacyl-CoA when NAD is solely present, and [[acetyl-CoA]] when NAD and [[CoASH]] are present. <ref>{{cite journal |last1 vauthors = Carpenter|first1= K|last2=, Pollitt|first2= RJ|last3=, Middleton|first3= B | title = Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria. | journal = Biochemical and biophysicalBiophysical researchResearch communications|date=16 MarchCommunications 1992| volume = 183 | issue = 2 | pages =443-8 443–8 | date = Mar 1992 | pmid = 1550553 | doi=10.1016/0006-291x(92)90501-b}}</ref> The alpha subunit catalyzes this reaction, and is attached to [[HADHB]], which catalyzes the last step of the reaction.<ref name="BioChem">{{cite book | title = Principles of Biochemistry | chapter = Chapter 18, Mitochondrial ATP synthesis | first1 = Donald J. | last1 = Voet | first2 = Judith G. | last2 = Voet | first3 = Charlotte W. | last3 = Pratt | publisher = Wiley | year = 2010 | isbn = 978-0-470-23396-2 | page = 669 | edition = 4th | name-list-style = vanc }}</ref>

Mutations in this gene result in trifunctional protein deficiency or [[long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency]]. .<ref name="entrez"/>

* {{vcite2cite journal | vauthors = IJlstRakheja LD, OostheimBennett WMJ, Ruiter JP,Rogers Wanders RJBB | title = Molecular basis of longLong-chain L-3-hydroxyacyl-CoAcoenzyme a dehydrogenase deficiency: identificationa ofmolecular twoand newbiochemical mutationsreview | journal = JournalLaboratory of Inherited Metabolic DiseaseInvestigation | volume = 2082 | issue = 37 | date = Jul 19972002 | pmid = 926637112118083 | doi=10.1097/01.lab.0000021175.50201.46 | pages=815–24| doi-access = free }}

* {{vcite2cite journal | vauthors = YagiIsaacs MJD, LeeSims THF, AwanoPowell HCK, TsujiBennett MMJ, TajimaHale GDE, KobayashiTreem HWR, HasegawaStrauss Y,AW Yamaguchi| S,title Takeshima= Y,Maternal Matsuoacute Mfatty |liver title =of Apregnancy patientassociated with mitochondrialfetal trifunctional protein deficiency: duemolecular tocharacterization theof mutationsa innovel thematernal HADHBmutant gene showed recurrent myalgia since early childhood and was diagnosed in adolescenceallele | journal = MolecularPediatric Genetics and MetabolismResearch | volume = 10440 | issue = 43 | date = DecSep 20111996 | pmid = 220007558865274 | doi = 10.10161203/j.ymgme.2011.09.02500006450-199609000-00005 | pages=393–8| doi-access = free }}