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Pathway Description
Valine, Leucine, and Isoleucine Degradation
Bos taurus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-08-30
Valine, isoleuciine, and leucine are essential amino acids and are identified as the branched-chain amino acids (BCAAs). The catabolism of all three amino acids starts in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with α-ketoglutarate as the amine acceptor. As a result, three different α-keto acids are produced and are oxidized using a common branched-chain α-keto acid dehydrogenase (BCKD), yielding the three different CoA derivatives. Isovaleryl-CoA is produced from leucine by these two reactions, alpha-methylbutyryl-CoA from isoleucine, and isobutyryl-CoA from valine. These acyl-CoA’s undergo dehydrogenation, catalyzed by three different but related enzymes, and the breakdown pathways then diverge. Leucine is ultimately converted into acetyl-CoA and acetoacetate; isoleucine into acetyl-CoA and succinyl-CoA; and valine into propionyl-CoA (and subsequently succinyl-CoA). Under fasting conditions, substantial amounts of all three amino acids are generated by protein breakdown. In muscle, the final products of leucine, isoleucine, and valine catabolism can be fully oxidized via the citric acid cycle; in the liver, they can be directed toward the synthesis of ketone bodies (acetoacetate and acetyl-CoA) and glucose (succinyl-CoA). Because isoleucine catabolism terminates with the production of acetyl-CoA and propionyl-CoA, it is both glucogenic and ketogenic. Because leucine gives rise to acetyl-CoA and acetoacetyl-CoA, it is classified as strictly ketogenic.
References
Valine, Leucine, and Isoleucine Degradation References
Nobukuni Y, Mitsubuchi H, Endo F, Asaka J, Oyama R, Titani K, Matsuda I: Isolation and characterization of a complementary DNA clone coding for the E1 beta subunit of the bovine branched-chain alpha-ketoacid dehydrogenase complex: complete amino acid sequence of the precursor protein and its proteolytic processing. Biochemistry. 1990 Feb 6;29(5):1154-60. doi: 10.1021/bi00457a009.
Pubmed: 2322554
Wynn RM, Chuang JL, Davie JR, Fisher CW, Hale MA, Cox RP, Chuang DT: Cloning and expression in Escherichia coli of mature E1 beta subunit of bovine mitochondrial branched-chain alpha-keto acid dehydrogenase complex. Mapping of the E1 beta-binding region on E2. J Biol Chem. 1992 Jan 25;267(3):1881-7.
Pubmed: 1730724
Hu CW, Lau KS, Griffin TA, Chuang JL, Fisher CW, Cox RP, Chuang DT: Isolation and sequencing of a cDNA encoding the decarboxylase (E1)alpha precursor of bovine branched-chain alpha-keto acid dehydrogenase complex. Expression of E1 alpha mRNA and subunit in maple-syrup-urine-disease and 3T3-L1 cells. J Biol Chem. 1988 Jun 25;263(18):9007-14.
Pubmed: 3379058
Pettit FH, Yeaman SJ, Reed LJ: Purification and characterization of branched chain alpha-keto acid dehydrogenase complex of bovine kidney. Proc Natl Acad Sci U S A. 1978 Oct;75(10):4881-5. doi: 10.1073/pnas.75.10.4881.
Pubmed: 283398
Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marcais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42. doi: 10.1186/gb-2009-10-4-r42. Epub 2009 Apr 24.
Pubmed: 19393038
Harhay GP, Sonstegard TS, Keele JW, Heaton MP, Clawson ML, Snelling WM, Wiedmann RT, Van Tassell CP, Smith TP: Characterization of 954 bovine full-CDS cDNA sequences. BMC Genomics. 2005 Nov 23;6:166. doi: 10.1186/1471-2164-6-166.
Pubmed: 16305752
Griffin TA, Lau KS, Chuang DT: Characterization and conservation of the inner E2 core domain structure of branched-chain alpha-keto acid dehydrogenase complex from bovine liver. Construction of a cDNA encoding the entire transacylase (E2b) precursor. J Biol Chem. 1988 Oct 5;263(28):14008-14.
Pubmed: 3049570
Lau KS, Griffin TA, Hu CW, Chuang DT: Conservation of primary structure in the lipoyl-bearing and dihydrolipoyl dehydrogenase binding domains of mammalian branched-chain alpha-keto acid dehydrogenase complex: molecular cloning of human and bovine transacylase (E2) cDNAs. Biochemistry. 1988 Mar 22;27(6):1972-81. doi: 10.1021/bi00406a025.
Pubmed: 2837277
Hummel KB, Litwer S, Bradford AP, Aitken A, Danner DJ, Yeaman SJ: Nucleotide sequence of a cDNA for branched chain acyltransferase with analysis of the deduced protein structure. J Biol Chem. 1988 May 5;263(13):6165-8.
Pubmed: 3245861
Agca C, Bidwell CA, Donkin SS: Cloning of bovine pyruvate carboxylase and 5' untranslated region variants. Anim Biotechnol. 2004 May;15(1):47-66. doi: 10.1081/ABIO-120037897.
Pubmed: 15248600
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000032
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