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MetaCyc Pathway: L-leucine degradation III
Inferred from experiment

Pathway diagram: L-leucine degradation III

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.

Synonyms: Ehrlich pathway

Superclasses: Degradation/Utilization/AssimilationAmino Acids DegradationProteinogenic Amino Acids DegradationL-leucine Degradation

Some taxa known to possess this pathway include : Saccharomyces cerevisiae

Expected Taxonomic Range: Fungi

While Saccharomyces cerevisiae can utilize only a limited range of carbon sources [Barnett92] it can obtain its nitrogen from many different sources, including most amino acids [Large68]. The most common mechanism for retrieving the nitrogen from amino acids is transamination, using 2-oxoglutarate or other 2-oxo acids as amino acceptors. This process leaves the carbon skeleton of the amino acid intact, in the form of a 2-oxo acid. In a few cases the resulting 2-oxo acid can be directly fed into central metabolism (such as the case of L-alanine and its derived 2-keto acid, pyruvate). In most cases, though, the 2-oxo acids resulting from transamination are not intermediates of central metabolism, and are excreted from the cells after some transformation.

An important and common pathway for catabolism of amino acids by yeast is the Ehrlich pathway [Ehrlich07]. In this pathway, following transamination of an amino acid into the corresponding 2-oxo acid, the 2-oxo acid is decarboxylated to an aldehyde. Depending on the redox status of the cells [Vuralhan03], the aldehydes can then be either reduced (by alcohol dehydrogenases) to alcohols, which are called collectively "fusel alcohols", or oxidized by aldehyde dehydrogenases to organic acids (fusel acids) [Vuralhan05].

L-leucine is one of the three protein-building branched chain amino acids (BCAAs), along with L-valine and L-isoleucine.

The metabolism of BCAA in yeast is different than in other eukaryotes. While most other eukaryotes (as well as many prokaryotes) catabolize L-leucine through a succession of acyl-coA derivatives to metabolites that can enter the TCA cycle (see L-leucine degradation I), providing the organism with carbon as well as nitrogen, yeast are not able to use L-leucine as a carbon source, and process it through the Ehtlich pathway to 3-methylbutanol [Dickinson97].

Initial work performed by Ehrlich and others suggested that the catabolism of L-leucine in Saccharomyces cerevisiae first involves transamination using 2-oxoglutarate (similar to the first step of the pathway found in other eukaryotes), but continues with decarboxylation of the keto acid to produce an aldehyde that is then reduced to 3-methylbutanol [Ehrlich07]. Later work by Dickinson et al suggests that the product of L-leucine transamination, 4-methyl-2-oxopentanoate, is decarboxylated by a pyruvate decarboxylase-like enzyme encoded by the THI3 gene [Dickinson97, Dickinson03]. Mutants lacking this enzyme were not able to grow in ethanol minimal medium with leucine as a sole nitrogen source [Dickinson97]. The mutants were able to grow in glucose minimal medium with leucine as the sole nitrogen source, but produced very little 3-methylbutanol (since some 3-methylbutanol was still formed, the authors speculate that there is at least one other decarboxylase that is involved in the decarboxylation of 4-methyl-2-oxopentanoate and the formation of 3-methylbutanol [Dickinson97].

Variants: L-leucine degradation I, L-leucine degradation II

Created 09-Jan-2006 by Caspi R, SRI International


Barnett92: Barnett JA (1992). "Some controls on oligosaccharide utilization by yeasts: the physiological basis of the Kluyver effect." FEMS Microbiol Lett 79(1-3);371-8. PMID: 1478472

Dickinson03: Dickinson JR, Salgado LE, Hewlins MJ (2003). "The catabolism of amino acids to long chain and complex alcohols in Saccharomyces cerevisiae." J Biol Chem 278(10);8028-34. PMID: 12499363

Dickinson97: Dickinson JR, Lanterman MM, Danner DJ, Pearson BM, Sanz P, Harrison SJ, Hewlins MJ (1997). "A 13C nuclear magnetic resonance investigation of the metabolism of leucine to isoamyl alcohol in Saccharomyces cerevisiae." J Biol Chem 272(43);26871-8. PMID: 9341119

Ehrlich07: Ehrlich, F. (1907). "Uber die Bedingungen der Fuselolbildung und uber ihren Zusammenhang mit dem Eiweissaufbau der Hefe." Ber. Dtsch. Chem. Ges. 40:1027-1047.

Large68: Large, P. J. (1968). "Degradation of organic nitrogen compounds by yeasts." Yeast 2:1-34.

Vuralhan03: Vuralhan Z, Morais MA, Tai SL, Piper MD, Pronk JT (2003). "Identification and characterization of phenylpyruvate decarboxylase genes in Saccharomyces cerevisiae." Appl Environ Microbiol 69(8);4534-41. PMID: 12902239

Vuralhan05: Vuralhan Z, Luttik MA, Tai SL, Boer VM, Morais MA, Schipper D, Almering MJ, Kotter P, Dickinson JR, Daran JM, Pronk JT (2005). "Physiological characterization of the ARO10-dependent, broad-substrate-specificity 2-oxo acid decarboxylase activity of Saccharomyces cerevisiae." Appl Environ Microbiol 71(6);3276-84. PMID: 15933030

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Bennetzen82: Bennetzen JL, Hall BD (1982). "The primary structure of the Saccharomyces cerevisiae gene for alcohol dehydrogenase." J Biol Chem 257(6);3018-25. PMID: 6277922

Breicha10: Breicha K, Muller M, Hummel W, Niefind K (2010). "Crystallization and preliminary crystallographic analysis of Gre2p, an NADP(+)-dependent alcohol dehydrogenase from Saccharomyces cerevisiae." Acta Crystallogr Sect F Struct Biol Cryst Commun 66(Pt 7);838-41. PMID: 20606287

Chen03a: Chen CN, Porubleva L, Shearer G, Svrakic M, Holden LG, Dover JL, Johnston M, Chitnis PR, Kohl DH (2003). "Associating protein activities with their genes: rapid identification of a gene encoding a methylglyoxal reductase in the yeast Saccharomyces cerevisiae." Yeast 20(6);545-54. PMID: 12722185

Cheraiti08: Cheraiti N, Sauvage FX, Salmon JM (2008). "Acetaldehyde addition throughout the growth phase alleviates the phenotypic effect of zinc deficiency in Saccharomyces cerevisiae." Appl Microbiol Biotechnol 77(5);1093-109. PMID: 17938904

Choi10: Choi YH, Choi HJ, Kim D, Uhm KN, Kim HK (2010). "Asymmetric synthesis of (S)-3-chloro-1-phenyl-1-propanol using Saccharomyces cerevisiae reductase with high enantioselectivity." Appl Microbiol Biotechnol 87(1);185-93. PMID: 20111861

Collier72: Collier RH, Kohlhaw G (1972). "Nonidentity of the aspartate and the aromatic aminotransferase components of transaminase A in Escherichia coli." J Bacteriol 1972;112(1);365-71. PMID: 4404056

Connor08: Connor MR, Liao JC (2008). "Engineering of an Escherichia coli strain for the production of 3-methyl-1-butanol." Appl Environ Microbiol 74(18);5769-75. PMID: 18676713

Dickinson00: Dickinson JR (2000). "Pathways of leucine and valine catabolism in yeast." Methods Enzymol 324;80-92. PMID: 10989420

Dickinson00a: Dickinson JR, Harrison SJ, Dickinson JA, Hewlins MJ (2000). "An investigation of the metabolism of isoleucine to active Amyl alcohol in Saccharomyces cerevisiae." J Biol Chem 275(15);10937-42. PMID: 10753893

Dickinson93: Dickinson JR, Norte V (1993). "A study of branched-chain amino acid aminotransferase and isolation of mutations affecting the catabolism of branched-chain amino acids in Saccharomyces cerevisiae." FEBS Lett 326(1-3);29-32. PMID: 8325383

Drewke88: Drewke C, Ciriacy M (1988). "Overexpression, purification and properties of alcohol dehydrogenase IV from Saccharomyces cerevisiae." Biochim Biophys Acta 950(1);54-60. PMID: 3282541

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

Feldmann94: Feldmann H, Aigle M, Aljinovic G, Andre B, Baclet MC, Barthe C, Baur A, Becam AM, Biteau N, Boles E (1994). "Complete DNA sequence of yeast chromosome II." EMBO J 13(24);5795-809. PMID: 7813418

Ganzhorn87: Ganzhorn AJ, Green DW, Hershey AD, Gould RM, Plapp BV (1987). "Kinetic characterization of yeast alcohol dehydrogenases. Amino acid residue 294 and substrate specificity." J Biol Chem 262(8);3754-61. PMID: 3546317

Hauser07: Hauser M, Horn P, Tournu H, Hauser NC, Hoheisel JD, Brown AJ, Dickinson JR (2007). "A transcriptome analysis of isoamyl alcohol-induced filamentation in yeast reveals a novel role for Gre2p as isovaleraldehyde reductase." FEMS Yeast Res 7(1);84-92. PMID: 16999827

Huh03: Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, O'Shea EK (2003). "Global analysis of protein localization in budding yeast." Nature 425(6959);686-91. PMID: 14562095

Inoue88: Inoue K, Kuramitsu S, Aki K, Watanabe Y, Takagi T, Nishigai M, Ikai A, Kagamiyama H (1988). "Branched-chain amino acid aminotransferase of Escherichia coli: overproduction and properties." J Biochem (Tokyo) 1988;104(5);777-84. PMID: 3069843

Johnston94: Johnston M, Andrews S, Brinkman R, Cooper J, Ding H, Dover J, Du Z, Favello A, Fulton L, Gattung S (1994). "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII." Science 265(5181);2077-82. PMID: 8091229

Kispal96: Kispal G, Steiner H, Court DA, Rolinski B, Lill R (1996). "Mitochondrial and cytosolic branched-chain amino acid transaminases from yeast, homologs of the myc oncogene-regulated Eca39 protein." J Biol Chem 271(40);24458-64. PMID: 8798704

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Sat Apr 30, 2016, biocyc11.