Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Threonine and 2-Oxobutanoate Degradation
Homo sapiens
Metabolic Pathway
2-oxobutanoate, also known as 2-Ketobutyric acid, is a 2-keto acid that is commonly produced in the metabolism of amino acids such as methionine and threonine. Like other 2-keto acids, degradation of 2-oxobutanoate occurs in the mitochondrial matrix and begins with oxidative decarboxylation to its acyl coenzyme A derivative, propionyl-CoA. This reaction is mediated by a class of large, multienzyme complexes called 2-oxo acid dehydrogenase complexes. While no 2-oxo acid dehydrogenase complex is specific to 2-oxobutanoate, numerous complexes can catalyze its reaction. In this pathway the branched-chain alpha-keto acid dehydrogenase complex is depicted. All 2-oxo acid dehydrogenase complexes consist of three main components: a 2-oxo acid dehydrogenase (E1) with a thiamine pyrophosphate cofactor, a dihydrolipoamide acyltransferase (E2) with a lipoate cofactor, and a dihydrolipoamide dehydrogenase (E3) with a flavin cofactor. E1 binds the 2-oxobutanoate to the lipoate on E2, which then transfers the propionyl group to coenzyme A, producing propionyl-CoA and reducing the lipoate. E3 then transfers protons to NAD in order to restore the lipoate. Propionyl-CoA carboxylase transforms the propionyl-CoA to S-methylmalonyl-CoA, which is then converted to R-methylmalonyl-CoA via methylmalonyl-CoA epimerase. In the final step, methylmalonyl-CoA mutase acts on the R-methylmalonyl-CoA to produce succinyl-CoA.
References
Threonine and 2-Oxobutanoate Degradation References
Bobik TA, Rasche ME: Identification of the human methylmalonyl-CoA racemase gene based on the analysis of prokaryotic gene arrangements. Implications for decoding the human genome. J Biol Chem. 2001 Oct 5;276(40):37194-8. doi: 10.1074/jbc.M107232200. Epub 2001 Jul 31.
Pubmed: 11481338
de Kok A, Hengeveld AF, Martin A, Westphal AH: The pyruvate dehydrogenase multi-enzyme complex from Gram-negative bacteria. Biochim Biophys Acta. 1998 Jun 29;1385(2):353-66.
Pubmed: 9655933
Fries M, Jung HI, Perham RN: Reaction mechanism of the heterotetrameric (alpha2beta2) E1 component of 2-oxo acid dehydrogenase multienzyme complexes. Biochemistry. 2003 Jun 17;42(23):6996-7002. doi: 10.1021/bi027397z.
Pubmed: 12795594
Jansen R, Kalousek F, Fenton WA, Rosenberg LE, Ledley FD: Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction. Genomics. 1989 Feb;4(2):198-205.
Pubmed: 2567699
Paxton R, Scislowski PW, Davis EJ, Harris RA: Role of branched-chain 2-oxo acid dehydrogenase and pyruvate dehydrogenase in 2-oxobutyrate metabolism. Biochem J. 1986 Mar 1;234(2):295-303.
Pubmed: 3718468
Zhou ZH, McCarthy DB, O'Connor CM, Reed LJ, Stoops JK: The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14802-7. doi: 10.1073/pnas.011597698.
Pubmed: 11752427
Edgar AJ: The human L-threonine 3-dehydrogenase gene is an expressed pseudogene. BMC Genet. 2002 Oct 2;3:18. Epub 2002 Oct 2.
Pubmed: 12361482
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Settings