3-hydroxyisobutyrate dehydrogenase

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[5] that in humans is encoded by the HIBADH gene.[6]

3-hydroxyisobutyrate dehydrogenase
Identifiers
EC number	1.1.1.31
CAS number	9028-39-1
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

HIBADH
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2GF2, 2I9P
Identifiers
Aliases	HIBADH, Hibadh, 6430402H10Rik, AI265272, NS5ATP1, 3-hydroxyisobutyrate dehydrogenase
External IDs	OMIM: 608475 MGI: 1889802 HomoloGene: 15088 GeneCards: HIBADH
EC number	1.1.1.31
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p15.2 Start 27,525,442 bp[1] End 27,662,883 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 B3 Start 52,546,228 bp[2] End 52,640,389 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • 3-hydroxyisobutyrate dehydrogenase activity • oxidoreductase activity • NAD binding • phosphogluconate dehydrogenase (decarboxylating) activity • NADP binding • oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Cellular component • mitochondrial matrix • mitochondrion Biological process • valine catabolic process • branched-chain amino acid catabolic process • oxidation-reduction process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	11112	58875
Ensembl	ENSG00000106049	ENSMUSG00000029776
UniProt	P31937	Q99L13
RefSeq (mRNA)	NM_152740	NM_145567
RefSeq (protein)	NP_689953	NP_663542
Location (UCSC)	Chr 7: 27.53 – 27.66 Mb	Chr 6: 52.55 – 52.64 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

3-Hydroxyisobutyrate dehydrogenase catalyzes the chemical reaction:

3-hydroxy-2-methylpropanoate + NAD⁺ ${\displaystyle \rightleftharpoons }$ 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.[6]

Structural studies

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

References

1. GRCh38: Ensembl release 89: ENSG00000106049 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029776 - 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. Robinson WG, Coon MJ (March 1957). "The purification and properties of beta-hydroxyisobutyric dehydrogenase". J. Biol. Chem. 225 (1): 511–21. PMID 13416257.
6. "Entrez Gene: HIBADH 3-hydroxyisobutyrate dehydrogenase".

Further reading

• 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. Bibcode:2003Natur.424..157H. 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. Bibcode:2003Sci...300..767S. 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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Sanger Centre, The; Washington University Genome Sequencing Cente, The (1999). "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. 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.

External links

• Human HIBADH genome location and HIBADH gene details page in the UCSC Genome Browser.
• PDBe-KB provides an overview of all the structure information available in the PDB for Human 3-hydroxyisobutyrate dehydrogenase, mitochondrial