This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Degradation/Utilization/Assimilation → Amino Acids Degradation → Proteinogenic Amino Acids Degradation → L-isoleucine Degradation|
Some taxa known to possess this pathway include : Bacillus subtilis, Bos taurus, Clostridium, Homo sapiens, Pseudomonas, Pseudomonas aeruginosa, Pseudomonas putida, Rattus norvegicus, Salmonella enterica enterica serovar Typhimurium, Streptomyces avermitilis, Sulfolobus solfataricus
L-isoleucine is one of the three main branched chain amino acids (BCAAs), along with L-leucine and L-valine. The catabolic pathways of the BCAAs can be divided into two sequential series of reactions, referred to as the common pathway and the distal pathway.
The common pathway includes the enzymes branched-chain-amino-acid aminotransferase, branched-chain α-keto acid dehydrogenase complex, and 2-methylacyl-CoA dehydrogenase. These three enzymes catalyze the conversion of all three BCAAs to their respective acyl-CoA derivatives ( methylacrylyl-CoA, 3-methylcrotonyl-CoA, and (E)-2-methylcrotonoyl-CoA for L-valine, L-leucine, and L-isoleucine, respectively), though the intermediates formed by these enzymes are different for the different amino acids. The distal parts of the pathways are completely different for the three BCAAs, and comprise enzymes specific for each amino acid [Massey76].
This Isoleucine degradation pathway is wide spread, and is found in many microorganisms, higher plants, and animals (including mammals).
The catabolism of L-isoleucine begins with its transamination to (S)-3-methyl-2-oxopentanoate, followed by oxidative decarboxylation to 2-methylbutanoyl-CoA. 2-methylbutanoyl-CoA then undergoes a four-step β oxidation process, involving dehydrogenation to (E)-2-methylcrotonoyl-CoA, hydration to 2-methyl-3-hydroxybutyryl-CoA, dehydrogenation to 2-methylacetoacetyl-CoA, and finally a thioester hydrolysis forming acetyl-CoA and propanoyl-CoA [Conrad74].
Variants: L-isoleucine degradation II
AEvarsson00: AEvarsson A, Chuang JL, Wynn RM, Turley S, Chuang DT, Hol WG (2000). "Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease." Structure 8(3);277-91. PMID: 10745006
Battaile04: Battaile KP, Nguyen TV, Vockley J, Kim JJ (2004). "Structures of isobutyryl-CoA dehydrogenase and enzyme-product complex: comparison with isovaleryl- and short-chain acyl-CoA dehydrogenases." J Biol Chem 279(16);16526-34. PMID: 14752098
Chang02a: Chang CF, Chou HT, Chuang JL, Chuang DT, Huang TH (2002). "Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain alpha-keto acid dehydrogenase complex." J Biol Chem 277(18);15865-73. PMID: 11839747
Chang06a: Chang CF, Chou HT, Lin YJ, Lee SJ, Chuang JL, Chuang DT, Huang TH (2006). "Structure of the subunit binding domain and dynamics of the di-domain region from the core of human branched chain alpha-ketoacid dehydrogenase complex." J Biol Chem 281(38);28345-53. PMID: 16861235
Chen94a: Chen D, Swenson RP (1994). "Cloning, sequence analysis, and expression of the genes encoding the two subunits of the methylotrophic bacterium W3A1 electron transfer flavoprotein." J Biol Chem 269(51);32120-30. PMID: 7798207
Chuang94: Chuang JL, Fisher CR, Cox RP, Chuang DT (1994). "Molecular basis of maple syrup urine disease: novel mutations at the E1 alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex." Am J Hum Genet 55(2);297-304. PMID: 8037208
Chuang95: Chuang JL, Davie JR, Chinsky JM, Wynn RM, Cox RP, Chuang DT (1995). "Molecular and biochemical basis of intermediate maple syrup urine disease. Occurrence of homozygous G245R and F364C mutations at the E1 alpha locus of Hispanic-Mexican patients." J Clin Invest 95(3);954-63. PMID: 7883996
Chuang96: Chuang JL, Cox RP, Chuang DT (1996). "Maple syrup urine disease: the E1beta gene of human branched-chain alpha-ketoacid dehydrogenase complex has 11 rather than 10 exons, and the 3' UTR in one of the two E1beta mRNAs arises from intronic sequences." Am J Hum Genet 58(6);1373-7. PMID: 8651316
Dakoji01: Dakoji S, Li D, Agnihotri G, Zhou HQ, Liu HW (2001). "Studies on the inactivation of bovine liver enoyl-CoA hydratase by (methylenecyclopropyl)formyl-CoA: elucidation of the inactivation mechanism and identification of cysteine-114 as the entrapped nucleophile." J Am Chem Soc 123(40);9749-59. PMID: 11583536
Danner89: Danner DJ, Litwer S, Herring WJ, Pruckler J (1989). "Construction and nucleotide sequence of a cDNA encoding the full-length preprotein for human branched chain acyltransferase." J Biol Chem 264(13);7742-6. PMID: 2708389
Dariush91: Dariush N, Fisher CW, Cox RP, Chuang DT (1991). "Structure of the gene encoding the entire mature E1 alpha subunit of human branched-chain alpha-keto acid dehydrogenase complex." FEBS Lett 284(1);34-8. PMID: 2060625
Eden96: Eden A, Simchen G, Benvenisty N (1996). "Two yeast homologs of ECA39, a target for c-Myc regulation, code for cytosolic and mitochondrial branched-chain amino acid aminotransferases." J Biol Chem 271(34);20242-5. PMID: 8702755
Ensenauer02: Ensenauer R, Niederhoff H, Ruiter JP, Wanders RJ, Schwab KO, Brandis M, Lehnert W (2002). "Clinical variability in 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency." Ann Neurol 51(5);656-9. PMID: 12112118
Fiedler02: Fiedler S, Steinbuchel A, Rehm BH (2002). "The role of the fatty acid beta-oxidation multienzyme complex from Pseudomonas oleovorans in polyhydroxyalkanoate biosynthesis: molecular characterization of the fadBA operon from P. oleovorans and of the enoyl-CoA hydratase genes phaJ from P. oleovorans and Pseudomonas putida." Arch Microbiol 178(2);149-60. PMID: 12115060
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