3-hydroxyisobutyrate dehydrogenase explained

3-hydroxyisobutyrate dehydrogenase
Ec Number:	1.1.1.31
Cas Number:	9028-39-1
Go Code:	0008442

In enzymology, a 3-hydroxyisobutyrate dehydrogenase 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, five structures have been solved for this class of enzymes, with PDB accession codes,,,, and .

Further reading

• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Hillier LW, Fulton RS, Fulton LA . The DNA sequence of human chromosome 7. . Nature . 424 . 6945 . 157–64 . 2003 . 12853948 . 10.1038/nature01782 . 2003Natur.424..157H . etal. free .
• Scherer SW, Cheung J, MacDonald JR . Human chromosome 7: DNA sequence and biology. . Science . 300 . 5620 . 767–72 . 2003 . 12690205 . 10.1126/science.1083423 . 2882961 . 2003Sci...300..767S . etal.
• Mammalian Gene Collection Program Team . 4 . Strausberg . R. L. . Feingold . E. A. . Grouse . L. H. . Derge . J. G. . Klausner . R. D. . Collins . F. S. . Wagner . L. . Shenmen . C. M. . Schuler . G. D. . 10.1073/pnas.242603899 . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . . 99 . 26 . 16899–16903 . 139241 . 2002 . 12477932. 2002PNAS...9916899M . free .
• Toward a complete human genome sequence. . Genome Res. . 8 . 11 . 1097–108 . 1999 . 9847074 . 10.1101/gr.8.11.1097. Sanger Centre . The . Washington University Genome Sequencing Cente . The . free .
• Hughes GJ, Frutiger S, Paquet N . Human liver protein map: update 1993. . Electrophoresis . 14 . 11 . 1216–22 . 1994 . 8313870 . 10.1002/elps.11501401181 . 33424554 . etal.
• Rougraff PM, Paxton R, Kuntz MJ . Purification and characterization of 3-hydroxyisobutyrate dehydrogenase from rabbit liver. . J. Biol. Chem. . 263 . 1 . 327–31 . 1988 . 10.1016/S0021-9258(19)57396-3 . 3335502 . etal. free .
• Rougraff PM, Zhang B, Kuntz MJ . 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 . 1989 . 10.1016/S0021-9258(18)83634-1 . 2647728 . etal. free .

External links

• • PDBe-KB provides an overview of all the structure information available in the PDB for Human 3-hydroxyisobutyrate dehydrogenase, mitochondrial

Notes and References

1. Robinson WG, Coon MJ . The purification and properties of beta-hydroxyisobutyric dehydrogenase . J. Biol. Chem. . 225 . 1 . 511–21 . March 1957 . 10.1016/S0021-9258(18)64948-8 . 13416257 . free .
2. Web site: Entrez Gene: HIBADH 3-hydroxyisobutyrate dehydrogenase.