Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.1.1.35

Official Name

3-hydroxyacyl-CoA dehydrogenase

Name from literature

acyl-CoA dehydrogenase

Pathway from literature

mitochondrial beta-oxidation

Pathway from KEGG

Xenobiotics Biodegradation and Metabolism; Caprolactam degradation; map00930

Lipid Metabolism; Fatty acid metabolism; map00071

Xenobiotics Biodegradation and Metabolism; Benzoate degradation via CoA ligation; map00632

Xenobiotics Biodegradation and Metabolism; Geraniol degradation; map00281

Lipid Metabolism; alpha-Linolenic acid metabolism; map00592

Lipid Metabolism; Fatty acid elongation in mitochondria; map00062

Amino Acid Metabolism; Tryptophan metabolism; map00380

Amino Acid Metabolism; Valine, leucine and isoleucine degradation; map00280

Amino Acid Metabolism; Lysine degradation; map00310

Carbohydrate Metabolism; Butanoate metabolism; map00650

Organisms

Human (9606)

Genome localization

Xp11.2[3028 ], 3q26.3-q28[1962 ], 5q21[3295 ], 4q22-q26[3033 ],

Comments

Also oxidizes S-3-hydroxyacyl-N-acylthioethanolamine and S-3-hydroxyacyl-hydrolipoate. Some enzymes act, more slowly, with NADP+. Broad specificity to acyl chain-length (cf. EC 1.1.1.211 [long-chain-3-hydroxyacyl-CoA dehydrogenase]).

Rate-limiting Description

"During oxidation of ." (U-14Chexadecanoate by normal human fibroblast mitochondria, only the saturated acyl-CoA and acylcarnitine esters can be detected, supporting the concept that the acyl-CoA dehydrogenase step is rate-limiting in mitochondrial beta-oxidation)

Regulatory Information

Upstream transcription factor

1938

Regulatory type

Detail

transcriptional factor;eEF2(1938)

"Regulation of oxidative enzyme activity and eukaryotic elongation factor 2 in human skeletal muscle: influence of gender and exercise." (15954989)

phosphorylation;

"asal transcriptional, translational, and/or post-translational control of CS and HAD seems to be gender-dependent." (15954989)

phosphorylation;

P51659:from_uniprot:3_Phosphoserine

phosphorylation;

P51659:from_uniprot:309_Phosphoserine

phosphorylation;

Q08426:from_uniprot:359_Phosphoserine

phosphorylation;

P51659

phosphorylation;

Q08426

Gene ontology

Gene ontology

GO:0006629 (P) lipid metabolic process [Q99714 ];
GO:0008709 (F) 7-alpha-hydroxysteroid dehydrogenase activity [Q99714 ];
GO:0050662 (F) coenzyme binding [Q58EZ5, Q16836, Q08426 ];
GO:0004303 (F) estradiol 17-beta-dehydrogenase activity [P51659 ];
GO:0033989 (F) 3alpha, 7alpha, 12alpha-trihydroxy-5beta-chol... [P51659 ];
GO:0005777 (C) peroxisome [Q08426 ];
GO:0003857 (F) 3-hydroxyacyl-CoA dehydrogenase activity [Q58EZ5, Q16836, Q08426, Q99714, P51659 ];
GO:0005515 (F) protein binding [Q99714, P51659 ];
GO:0005498 (F) sterol carrier activity [P51659 ];
GO:0016853 (F) isomerase activity [Q58EZ5, P51659 ];
GO:0004300 (F) enoyl-CoA hydratase activity [Q58EZ5, Q08426 ];
GO:0047015 (F) 3-hydroxy-2-methylbutyryl-CoA dehydrogenase... [Q99714 ];
GO:0005886 (C) plasma membrane [Q99714 ];
GO:0004165 (F) dodecenoyl-CoA delta-isomerase activity [Q08426 ];
GO:0006631 (P) fatty acid metabolic process [Q58EZ5, Q16836 ];
GO:0005759 (C) mitochondrial matrix [Q16836 ];
GO:0005782 (C) peroxisomal matrix [P51659 ];
GO:0055114 (P) oxidation reduction [Q58EZ5, Q16836, Q08426, Q99714, P51659 ];
GO:0015248 (F) sterol transporter activity [P51659 ];

Tissue expression

Tissue From HPRD

Colon [08372, 03514 ];
Occipital pole [02223 ];
Hippocampus [02223 ];
Corpus callosum [02223 ];
Cardiac muscle [08372, 02223 ];
Fetus [06125 ];
Islets of Langerhans [08372 ];
Testis [08372, 03514, 02223 ];
Brain [08372, 03514, 02223 ];
Spleen [08372, 03514 ];
Thalamus [02223 ];
Heart [08372, 03514, 02223 ];
Amygdala [02223 ];
Cerebellum [02223 ];
Lymphocyte [03514 ];
Pituitary gland [03514 ];
Thymus [08372, 03514 ];
Uterus [03514 ];
Substantia nigra [02223 ];
Cerebral cortex [02223 ];
Bone cell [03514 ];
Spinal cord [02223 ];
Leukocyte [08372 ];
Caudate nucleus [02223 ];
Putamen [02223 ];
Intestine [03514 ];
Temporal lobe [02223 ];
Liver [08372, 03514, 02223 ];
Skeletal muscle [08372, 03514, 02223 ];
Prostate [08372, 03514 ];
Kidney [08372, 03514, 02223, 06125 ];
Lung [08372, 03514, 02223 ];
Pancreas [08372, 03514, 02223 ];
Ovary [08372, 03514, 02223 ];
Placenta [08372, 03514, 02223 ];
Subthalamic nucleus [02223 ];
Frontal lobe [02223 ];

Tissue specificity

Expressed in normal tissues but is overexpressed in neurons affected in AD [Q99714 ];

Expressed in liver, kidney, pancreas, heart and skeletal muscle [Q16836 ];

Liver and kidney. Lower amounts seen in the brain [Q08426 ];

Present in many tissues with highest concentrations in liver, heart, prostate and testis [P51659 ];

Subcellular localization

Localization

mitochondrion [Q16836 ];

peroxisome [Q08426, P51659 ];

Disease relevance

Disease

Absent in patients suffering with peroxisomal disorders such as Zellweger syndrome, neonatal adrenoleukodystrophy and infantile Refsum disease [Q08426 ];

Defects in HADH are the cause of 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency (HADH deficiency) [MIM:231530]. HADH deficiency is a metabolic disorder with various clinical presentations including hypoglycemia, hepatoencephalopathy, myopathy or cardiomyopathy, and in some cases sudden death [Q16836 ];

Defects in HSD17B4 are a cause of D-bifunctional protein deficiency (DBPD) [MIM:261515]. DBPD is a disorder of peroxisomal fatty acid beta-oxidation [P51659 ];

A chromosomal microduplication involving HSD17B10 and HUWE1 is the cause of mental retardation X-linked type 17 (MRX17) [MIM:300705];
also known as mental retardation X-linked type 31 (MRX31). MRX17 is a non-syndromic form of mental retardation. Both genes are overexpressed in blood cells from affected individuals [Q99714 ];

Defects in HSD17B10 are the cause of X-linked syndromic mental retardation type 10 (MRXS10) [MIM:300220]. MRXS10 is characterized by mild mental retardation, choreoathetosis and abnormal behavior [Q99714 ];

Defects in HSD17B10 are the cause of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (MHBD deficiency) [MIM:300438]. MHBD deficiency leads to neurological abnormalities, including psychomotor retardation, and, in virtually all patients, loss of mental and motor skills [Q99714 ];

Defects in HADH are the cause of familial hyperinsulinemic hypoglycemia 4 (HHF4) [MIM:609975]. Inappropriately elevated insulin secretion is the hallmark of persistent hyperinsulinemic hypoglycemia of infancy (PHHI), also denoted congenital hyperinsulinism. PHHI is due to defective negative feedback regulation of insulin secretion by low glucose levels. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF4 should be easily recognizable by analysis of acylcarnitine species and that this disorder responds well to treatment with diazoxide. It provides the first "experiment of nature" that links impaired fatty acid oxidation to hyperinsulinism and that provides support for the concept that a lipid signaling pathway is implicated in the control of insulin secretion [Q16836 ];

Links

SwissProt

P51659; Q08426; Q16836; Q58EZ5; Q99714

Entrez Gene

1962; 3028; 3033; 3295

HPRD

03514; 08372; 06125; 02223



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min