3-hydroxyisobutyrate dehydrogenase

Gene ontology
Molecular function	• phosphogluconate dehydrogenase (decarboxylating) activity • 3-hydroxyisobutyrate dehydrogenase activity • NAD binding
Cellular component	• mitochondrial matrix
Biological process	• valine catabolic process • branched-chain amino acid catabolic process • cellular nitrogen compound metabolic process • small molecule metabolic process • oxidation-reduction process
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 7:
27.53 – 27.66 Mb

Chr 6:
52.55 – 52.64 Mb

PubMed search

In enzymology, a 3-hydroxyisobutyrate dehydrogenase (EC 1.1.1.31) also known as β-hydroxyisobutyrate dehydrogenase or 3-hydroxyisobutyrate dehydrogenase, mitochondrial (HIBADH) is an enzyme^[1] that in humans is encoded by the HIBADH gene.^[2]

3-Hydroxyisobutyrate dehydrogenase catalyzes the chemical reaction:

3-hydroxy-2-methylpropanoate + NAD⁺

\rightleftharpoons

2-methyl-3-oxopropanoate + NADH + H⁺

Thus, the two substrates of this enzyme are 3-hydroxy-2-methylpropanoate and NAD⁺, whereas its 3 products are 2-methyl-3-oxopropanoate, NADH, and H⁺.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is 3-hydroxy-2-methylpropanoate:NAD⁺ oxidoreductase. This enzyme participates in valine, leucine and isoleucine degradation.

Function

3-hydroxyisobutyrate dehydrogenase is a tetrameric mitochondrial enzyme that catalyzes the NAD⁺-dependent, reversible oxidation of 3-hydroxyisobutyrate, an intermediate of valine catabolism, to methylmalonate semialdehyde.^[2]

Structural studies

As of late 2007, 5 structures have been solved for this class of enzymes, with PDB accession codes 1WP4, 2CVZ, 2GF2, 2H78, and 2I9P.

References

↑ Robinson WG, Coon MJ (March 1957). "The purification and properties of beta-hydroxyisobutyric dehydrogenase". J. Biol. Chem. 225 (1): 511–21. PMID 13416257.
1 2 "Entrez Gene: HIBADH 3-hydroxyisobutyrate dehydrogenase".

Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Hillier LW, Fulton RS, Fulton LA; et al. (2003). "The DNA sequence of human chromosome 7.". Nature 424 (6945): 157–64. doi:10.1038/nature01782. PMID 12853948.
Scherer SW, Cheung J, MacDonald JR; et al. (2003). "Human chromosome 7: DNA sequence and biology.". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
Mammalian Gene Collection Program Team; Strausberg, R. L.; Feingold, E. A.; Grouse, L. H.; et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
"Toward a complete human genome sequence.". Genome Res. 8 (11): 1097–108. 1999. doi:10.1101/gr.8.11.1097. PMID 9847074.
Hughes GJ, Frutiger S, Paquet N; et al. (1994). "Human liver protein map: update 1993.". Electrophoresis 14 (11): 1216–22. doi:10.1002/elps.11501401181. PMID 8313870.
Rougraff PM, Paxton R, Kuntz MJ; et al. (1988). "Purification and characterization of 3-hydroxyisobutyrate dehydrogenase from rabbit liver.". J. Biol. Chem. 263 (1): 327–31. PMID 3335502.
Rougraff PM, Zhang B, Kuntz MJ; et al. (1989). "Cloning and sequence analysis of a cDNA for 3-hydroxyisobutyrate dehydrogenase. Evidence for its evolutionary relationship to other pyridine nucleotide-dependent dehydrogenases.". J. Biol. Chem. 264 (10): 5899–903. PMID 2647728.

PDB gallery

2gf2: Crystal structure of human hydroxyisobutyrate dehydrogenase

2i9p: Crystal structure of human hydroxyisobutyrate dehydrogenase complexed with NAD+

Oxidoreductases: alcohol oxidoreductases (EC 1.1)

1.1.1: NAD/NADP acceptor	3-hydroxyacyl-CoA dehydrogenase 3-hydroxybutyryl-CoA dehydrogenase Alcohol dehydrogenase Aldo-keto reductase 1A1 1B1 1B10 1C1 1C3 1C4 7A2 Aldose reductase Beta-Ketoacyl ACP reductase Carbohydrate dehydrogenases Carnitine dehydrogenase D-malate dehydrogenase (decarboxylating) DXP reductoisomerase Glucose-6-phosphate dehydrogenase Glycerol-3-phosphate dehydrogenase HMG-CoA reductase IMP dehydrogenase Isocitrate dehydrogenase Lactate dehydrogenase L-threonine dehydrogenase L-xylulose reductase Malate dehydrogenase Malate dehydrogenase (decarboxylating) Malate dehydrogenase (NADP+) Malate dehydrogenase (oxaloacetate-decarboxylating) Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) Phosphogluconate dehydrogenase 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	Malate dehydrogenase (quinone) Quinoprotein glucose dehydrogenase

1.1.99: other acceptors	Choline dehydrogenase L2HGDH

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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3-hydroxyisobutyrate dehydrogenase

Function

Structural studies

References

Further reading