Hydroxyacyl-Coenzyme A dehydrogenase

"HADH" redirects here. For hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha, see HADHA.

HADH
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1F0Y, 1F12, 1F14, 1F17, 1IL0, 1LSJ, 1LSO, 1M75, 1M76, 2HDH, 3HAD, 3RQS
Identifiers
Aliases	HADH , HAD, HADH1, HADHSC, HCDH, HHF4, MSCHAD, SCHAD, Hydroxyacyl-Coenzyme A dehydrogenase, hydroxyacyl-CoA dehydrogenase
External IDs	OMIM: 601609; MGI: 96009; HomoloGene: 55888; GeneCards: HADH; OMA:HADH - orthologs
Gene location (Human) Chr. Chromosome 4 (human) [1] Band 4q25 Start 107,989,714 bp [1] End 108,035,241 bp [1]
Gene location (Mouse) Chr. Chromosome 3 (mouse) [2] Band 3|3 G3 Start 131,027,068 bp [2] End 131,065,750 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in islet of Langerhans right ventricle Skeletal muscle tissue of rectus abdominis mucosa of transverse colon beta cell thoracic diaphragm kidney tubule vastus lateralis muscle body of tongue myocardium of left ventricle Top expressed in Paneth cell condyle medullary collecting duct tunica adventitia of aorta brown adipose tissue cumulus cell atrioventricular junction fossa migratory enteric neural crest cell renal corpuscle More reference expression data BioGPS n/a
Gene ontology Molecular function oxidoreductase activity 3-hydroxyacyl-CoA dehydrogenase activity NAD+ binding Cellular component cytoplasm mitochondrial matrix mitochondrion nucleoplasm Biological process response to insulin response to hormone fatty acid beta-oxidation negative regulation of insulin secretion response to activity fatty acid metabolic process lipid metabolism positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3033 15107 Ensembl ENSG00000138796 ENSMUSG00000027984 UniProt Q16836 Q61425 RefSeq (mRNA) NM_001184705 NM_005327 NM_001331027 NM_008212 RefSeq (protein) NP_001171634 NP_001317956 NP_005318 NP_032238 Location (UCSC) Chr 4: 107.99 – 108.04 Mb Chr 3: 131.03 – 131.07 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Hydroxyacyl-Coenzyme A dehydrogenase (HADH) is an enzyme which in humans is encoded by the HADH gene. ^{[5] [6]}

Structure

The HADH gene is located on the 4th chromosome, with its specific location being identified as 4q22-q26. The gene has 10 exons. ^[7] The HADH gene encodes a 34.3 kDa protein that has 314 amino acids and 124 observed peptides. ^{[8] [9]}

Function

This gene is a member of the 3-hydroxyacyl-CoA dehydrogenase gene family. The encoded protein functions in the mitochondrial matrix to catalyze the oxidation of straight-chain 3-hydroxyacyl-CoAs as part of the beta-oxidation pathway. Its enzymatic activity is highest with medium-chain-length fatty acids. ^[7]

Clinical significance

Mutations in this gene cause one form of familial hyperinsulinemic hypoglycemia. ^[10] A deficiency is associated with 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. Mutations also cause 3-hydroxyacyl-CoA dehydrogenase deficiency. There are a wide variety of mutations that have been identified to cause this disease. Among them are missense mutations (A40T, P258L, D57G, Y226H) and nonsense mutations (R236X) in the protein, and splicing mutations (261+1G>A, 710-2A>G) and some small deletions (587delC) in the cDNA. ^[11] One mutation, 636+471G>T in the HADH gene, was shown to create a cryptic splice donor site and an out-of-frame pseudoexon. ^[12] Most of the described cases have homozygous mutations. This disease has fairly homogenous clinical presentation across cases. The symptoms first appear in early life, between 1.5 hours post birth and 3 years of age, and the most common symptoms are hypoglycemia and seizures/convulsions directly related to the hypoglycemia. There are other clinical presentations that have been identified, namely: myoglobinuria, dicarboxylic aciduria, feeding difficulties in infancy, muscular hypotonia, hepatic steatosis, growth delay, hypertrophic cardiomyopathy, dilated cardiomyopathy, hepatic necrosis, and fulminant hepatic failure. The disorder may be diagnosed by either the analysis of the molecular genetics of the individual, or by detection of abnormal metabolite levels in blood and/or plasma. Individuals with this deficiency have an elevated amount of 3-hydroxyglutarate excreted through the urine; a heightened level of C4-OH acylcarnitine in the blood plasma is also a characteristic of this FAO disorder. Most documented cases thus far have shown that individuals are responsive to diazoxide treatment, and highlight the need for diagnosis and treatment administration as early as possible in order to correct hypoglycemia and avoid irreversible brain damage. ^[11]

Interactions

HADH has been shown to interact with Vpr, such that HIV-1 Vpr regulates mitochondrial respiration and enhances the activity of hydroxyacyl-CoA dehydrogenase (HADH) through PPARbeta/delta. ^[13]

See also

• 3-hydroxyacyl-CoA dehydrogenase
• hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit

References

1. GRCh38: Ensembl release 89: ENSG00000138796 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027984 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Craig I, Tolley E, Bobrow M (1976). "A preliminary analysis of the segregation of human hydroxyacyl coenzyme A dehydrogenase in human-mouse somatic cell hybrids". Cytogenetics and Cell Genetics. 16 (1–5): 114–7. doi:10.1159/000130568. PMID   975867.
6. Yang SY, He XY, Schulz H (Oct 2005). "3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease". The FEBS Journal. 272 (19): 4874–83. doi: 10.1111/j.1742-4658.2005.04911.x . PMID   16176262. S2CID   45683141.
7. "Entrez Gene: HADH".
8. 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 (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC   4076475 . PMID   23965338.
9. "Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2015-09-24. Retrieved 2015-03-23.
10. Molven A, Matre GE, Duran M, Wanders RJ, Rishaug U, Njølstad PR, Jellum E, Søvik O (Jan 2004). "Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation". Diabetes. 53 (1): 221–7. doi: 10.2337/diabetes.53.1.221 . PMID   14693719.
11. Martins E, Cardoso ML, Rodrigues E, Barbot C, Ramos A, Bennett MJ, Teles EL, Vilarinho L (Jun 2011). "Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: the clinical relevance of an early diagnosis and report of four new cases". Journal of Inherited Metabolic Disease. 34 (3): 835–42. doi:10.1007/s10545-011-9287-7. PMID   21347589. S2CID   36618116.
12. Flanagan SE, Xie W, Caswell R, Damhuis A, Vianey-Saban C, Akcay T, Darendeliler F, Bas F, Guven A, Siklar Z, Ocal G, Berberoglu M, Murphy N, O'Sullivan M, Green A, Clayton PE, Banerjee I, Clayton PT, Hussain K, Weedon MN, Ellard S (Jan 2013). "Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation". American Journal of Human Genetics. 92 (1): 131–6. doi:10.1016/j.ajhg.2012.11.017. PMC   3542457 . PMID   23273570.
13. Shrivastav S, Zhang L, Okamoto K, Lee H, Lagranha C, Abe Y, Balasubramanyam A, Lopaschuk GD, Kino T, Kopp JB (Sep 2013). "HIV-1 Vpr enhances PPARβ/δ-mediated transcription, increases PDK4 expression, and reduces PDC activity". Molecular Endocrinology. 27 (9): 1564–76. doi:10.1210/me.2012-1370. PMC   3753422 . PMID   23842279.

External links

• GeneReviews/NCBI/NIH/UW entry on Familial Hyperinsulinism
• Overview of all the structural information available in the PDB for UniProt : Q16836 (Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial) at the PDBe-KB .

This article incorporates text from the United States National Library of Medicine, which is in the public domain.