3-hydroxyacyl-CoA dehydrogenase

Hydroxyacyl-Coenzyme A dehydrogenase

PDB rendering based on 3had.
Identifiers
Symbol	HADH
Alt. symbols	HADHSC
Entrez	3033
HUGO	4799
OMIM	601609
RefSeq	NM_005327
UniProt	Q16836
Other data
EC number	1.1.1.35
Locus	Chr. 4 q22-q26

In enzymology, a 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) is an enzyme that catalyzes the chemical reaction

(S)-3-hydroxyacyl-CoA + NAD⁺ $\rightleftharpoons$ 3-oxoacyl-CoA + NADH + H⁺

Thus, the two substrates of this enzyme are (S)-3-hydroxyacyl-CoA and NAD⁺, whereas its 3 products are 3-oxoacyl-CoA, NADH, and H⁺.

This enzyme belongs to the family of oxidoreductases, to be specific those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor.

1 Isozymes
2 Function
3 Metabolic pathways
4 Nomenclature
5 Structural studies
6 References

Isozymes

In humans, the following genes encode proteins with 3-hydroxyacyl-CoA dehydrogenase activity:

HADH – Hydroxyacyl-Coenzyme A dehydrogenase
HSD17B10 – 3-Hydroxyacyl-CoA dehydrogenase type-2
EHHADH – Peroxisomal bifunctional enzyme
HSD17B4 – Peroxisomal multifunctional enzyme type 2

Function

3-Hydroxyacyl CoA dehydrogenase is classified as an oxidoreductase.It is involved in fatty acid metabolic processes. Specifically it catalyzes the third step of beta oxidation; the oxidation of L-3-hydroxyacyl CoA by NAD⁺. The reaction converts the hydroxyl group into a keto group.

The end product is 3-ketoacyl CoA.

Metabolic pathways

This enzyme participates in 8 metabolic pathways:

fatty acid elongation in mitochondria
fatty acid metabolism
valine, leucine and isoleucine degradation
lysine degradation
tryptophan metabolism
benzoate degradation via coa ligation
butanoate metabolism
caprolactam degradation

Nomenclature

The systematic name of this enzyme class is (S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase. Other names in common use include:

1-specific DPN-linked beta-hydroxybutyric dehydrogenase
3-hydroxyacetyl-coenzyme A dehydrogenase
3-hydroxyacyl coenzyme A dehydrogenase
3-hydroxybutyryl-CoA dehydrogenase
3-hydroxyisobutyryl-CoA dehydrogenase
3-keto reductase
3-L-hydroxyacyl-CoA dehydrogenase
3beta-hydroxyacyl coenzyme A dehydrogenase
beta-hydroxy acid dehydrogenase
beta-hydroxyacyl CoA dehydrogenase
beta-hydroxyacyl dehydrogenase
beta-hydroxyacyl-coenzyme A synthetase
beta-hydroxyacylcoenzyme A dehydrogenase
beta-hydroxybutyrylcoenzyme A dehydrogenase
beta-keto-reductase
beta-ketoacyl-CoA reductase
L-3-hydroxyacyl CoA dehydrogenase
L-3-hydroxyacyl coenzyme A dehydrogenase

Structural studies

As of 20 January 2010, 22 structures have been solved for this class of enzymes, with PDB accession codes 1F0Y, 1F12, 1F14, 1F17, 1F67, 1GZ6, 1IKT, 1IL0, 1LSJ, 1LSO, 1M75, 1M76, 1S9C, 1WDK, 1WDL, 1WDM, 1ZBQ, 1ZCJ, 2D3T, 2HDH, 3HAD, and 3HDH.

References

Hillmer P and Gottschalk G (1974). "Solubilization and partial characterisation of particulate dehydrogenases from Clostridium kluyveri". Biochim. Biophys. Acta 334: 12–23.
Lehninger AL, Greville GD (1953). "The enzymic oxidation of alpha- and 2-beta-hydroxybutyrate". Biochim. Biophys. Acta 12 (1-2): 188–202. doi:10.1016/0006-3002(53)90138-3. PMID 13115428.
Stern JR (November 1957). "Crystalline beta-hydroxybutyryl dehydrogenase from pig heart". Biochim. Biophys. Acta 26 (2): 448–9. doi:10.1016/0006-3002(57)90040-9. PMID 13499396.
Wakil SJ, Green DE, Mii S and Mahler HR (April 1954). "Studies on the fatty acid oxidizing system of animal tissues. VI. beta-Hydroxyacyl coenzyme A dehydrogenase". J. Biol. Chem. 207 (2): 631–8. PMID 13163047.

Oxidoreductases: alcohol oxidoreductases (EC 1.1)

1.1.1: NAD/NADP acceptor	Alcohol dehydrogenase · Aldo-keto reductase (1A1, 1B1, 1B10, 1C1, 1C3, 1C4, 7A2) · Aldose reductase · Carbohydrate dehydrogenases · Carnitine dehydrogenase · DXP reductoisomerase · Glucose-6-phosphate dehydrogenase · Glycerol-3-phosphate dehydrogenase · HMG-CoA reductase · 3-hydroxyacyl-CoA dehydrogenase · Beta-hydroxybutyryl-CoA dehydrogenase · Isocitrate dehydrogenase · IMP dehydrogenase · Β-Ketoacyl ACP reductase · Lactate dehydrogenase · Malate dehydrogenase · Phosphogluconate dehydrogenase · L-threonine dehydrogenase · L-xylulose reductase · Sorbitol dehydrogenase Hydroxysteroid dehydrogenase: 3 Beta (3-beta-HSD, NSDHL) · 11 Beta (HSD11B1, HSD11B2) · 17 Beta

1.1.2: cytochrome acceptor	D-lactate dehydrogenase (cytochrome) · D-lactate dehydrogenase (cytochrome c-553) · Mannitol dehydrogenase (cytochrome)

1.1.3: oxygen acceptor	Glucose oxidase · L-gulonolactone oxidase · Xanthine oxidase

1.1.4: disulfide as acceptor	Vitamin K epoxide reductase · Vitamin-K-epoxide reductase (warfarin-insensitive)

1.1.5: quinone/similar acceptor	Quinoprotein glucose dehydrogenase

1.1.99: other acceptors	Choline dehydrogenase · L2HGDH

B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6

Metabolism: lipid metabolism / fatty acid metabolism · triglyceride and fatty acid enzymes

Synthesis

Malonyl-CoA synthesis	ATP citrate lyase · Acetyl-CoA carboxylase

Fatty acid synthesis/ Fatty acid synthase	Beta-ketoacyl-ACP synthase · Β-Ketoacyl ACP reductase · 3-Hydroxyacyl ACP dehydrase · Enoyl ACP reductase

Fatty acid desaturases	Stearoyl-CoA_desaturase-1

Triacyl glycerol	Glycerol-3-phosphate dehydrogenase · Thiokinase

Degradation

Acyl transport

Carnitine palmitoyltransferase I · Carnitine-acylcarnitine translocase · Carnitine palmitoyltransferase II

Beta oxidation

General	Acyl CoA dehydrogenase (ACADL, ACADM, ACADS, ACADVL, ACADSB) · Enoyl-CoA hydratase MTP: HADH · HADHA · HADHB Acetyl-CoA C-acyltransferase

Unsaturated	Enoyl CoA isomerase · 2,4 Dienoyl-CoA reductase

Odd chain	Propionyl-CoA carboxylase

Other	Hydroxyacyl-Coenzyme A dehydrogenase

To acetyl-CoA

Malonyl-CoA decarboxylase

Aldehydes

Long-chain-aldehyde dehydrogenase

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)