MetaCyc Pathway: methylglyoxal degradation VI
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: methylglyoxal degradation VI

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/AssimilationAldehyde Degradation
DetoxificationMethylglyoxal Detoxification

Some taxa known to possess this pathway include : Capra hircus, Homo sapiens, Mammalia, Rattus norvegicus

Expected Taxonomic Range: Mammalia

General Background

Methylglyoxal is produced in small amounts during glycolysis (via glycerone phosphate), fatty acid metabolism (via acetone), and protein metabolism (via aminoacetone). Methylglyoxal is highly toxic, most likely as a result of its interaction with protein side chains (see [Kalapos99] for a review). There are several pathways for the detoxification of methylglyoxal, based on different enzymes that are able to convert methylglyoxal to less toxic compounds. These enzymes include glyoxalase enzymes, methylglyoxal reductases, aldose reductases, aldehyde reductases and methylglyoxal dehydrogenases.

About This Pathway

This pathway is different from the pathways methylglyoxal degradation IV and methylglyoxal degradation V in that (R)-lactaldehyde and (R)-lactate are involved, rather than the L-specific isomers.

Methylglyoxal reductase enzymes that are specific for the D-form of lactaldehyde have been purified from rat liver [Ting65] and goat liver [Ray84a]. Both enzymes were specific for NADH (although the goat liver enzyme would accept NADPH, resulting in lower activity). The rat enzyme was isolated as catalyzing the reverse reaction (the oxidation of D-lactaldehyde to methylglyoxal), but that reaction was shown to be reversible.

While the rest of this pathway has not been characterized well, the presence of the enzymes required to metabolize (R)-lactaldehyde to pyruvate via (R)-lactate in mammalian cells is well documented [Sladek03, deBari02]. Some literature suggests that (R)-propane-1,2-diol is also a product of (R)-lactaldehyde metabolism [Ting64].

Variants: methylglyoxal degradation I, methylglyoxal degradation II, methylglyoxal degradation III, methylglyoxal degradation IV, methylglyoxal degradation V, methylglyoxal degradation VII, methylglyoxal degradation VIII

Created 18-Jan-2007 by Caspi R, SRI International


deBari02: de Bari L, Atlante A, Guaragnella N, Principato G, Passarella S (2002). "D-Lactate transport and metabolism in rat liver mitochondria." Biochem J 365(Pt 2);391-403. PMID: 11955284

Kalapos99: Kalapos MP (1999). "Methylglyoxal in living organisms: chemistry, biochemistry, toxicology and biological implications." Toxicol Lett 110(3);145-75. PMID: 10597025

Murata89: Murata K, Inoue Y, Rhee H, Kimura A (1989). "2-Oxoaldehyde metabolism in microorganisms." Can J Microbiol 35(4);423-31. PMID: 2663129

Ray84a: Ray M, Ray S (1984). "Purification and partial characterization of a methylglyoxal reductase from goat liver." Biochim Biophys Acta 802(1);119-27. PMID: 6386056

Sladek03: Sladek NE (2003). "Human aldehyde dehydrogenases: potential pathological, pharmacological, and toxicological impact." J Biochem Mol Toxicol 17(1);7-23. PMID: 12616643

Ting64: Ting, S.M., Sellinger, O.Z., Miller, O.N. (1964). "The metabolism of lactaldehyde. VI. The reduction of D- and L-lactaldehyde in rat liver." Biochim Biophys Acta 89;217-25. PMID: 14203169

Ting65: Ting, S.M., Miller, O.N., Sellinger, O.Z. (1965). "The metabolism of lactaldehyde. VII. The oxidation of D-lactaldehyde in rat liver." Biochim Biophys Acta 97;407-15. PMID: 14323585

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

Agarwal87: Agarwal DP, Goedde HW (1987). "Human aldehyde dehydrogenase isozymes and alcohol sensitivity." Isozymes Curr Top Biol Med Res 16;21-48. PMID: 3610592

Ambler91: Ambler RP (1991). "Sequence variability in bacterial cytochromes c." Biochim Biophys Acta 1058(1);42-7. PMID: 1646017

Ashibe07: Ashibe B, Hirai T, Higashi K, Sekimizu K, Motojima K (2007). "Dual subcellular localization in the endoplasmic reticulum and peroxisomes and a vital role in protecting against oxidative stress of fatty aldehyde dehydrogenase are achieved by alternative splicing." J Biol Chem 282(28);20763-73. PMID: 17510064

Braun87: Braun T, Bober E, Singh S, Agarwal DP, Goedde HW (1987). "Evidence for a signal peptide at the amino-terminal end of human mitochondrial aldehyde dehydrogenase." FEBS Lett 215(2);233-6. PMID: 3582651

Cameron86: Cameron, D.C., Cooney, C.L. (1986). "A novel fermentation: the production of (R)-1,2-propanediol and acetol by Clostridium thermosaccharolyticum." Nature Bio/Technology 4:651-654.

Chang97: Chang C, Yoshida A (1997). "Human fatty aldehyde dehydrogenase gene (ALDH10): organization and tissue-dependent expression." Genomics 40(1);80-5. PMID: 9070922

De96b: De Laurenzi V, Rogers GR, Hamrock DJ, Marekov LN, Steinert PM, Compton JG, Markova N, Rizzo WB (1996). "Sjogren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene." Nat Genet 12(1);52-7. PMID: 8528251

Ewaschuk05: Ewaschuk JB, Naylor JM, Zello GA (2005). "D-lactate in human and ruminant metabolism." J Nutr 135(7);1619-25. PMID: 15987839

Flick02: Flick MJ, Konieczny SF (2002). "Identification of putative mammalian D-lactate dehydrogenase enzymes." Biochem Biophys Res Commun 295(4);910-6. PMID: 12127981

Harada01a: Harada S (2001). "[Classification of alcohol metabolizing enzymes and polymorphisms--specificity in Japanese]." Nihon Arukoru Yakubutsu Igakkai Zasshi 36(2);85-106. PMID: 11398342

Hempel85: Hempel J, Kaiser R, Jornvall H (1985). "Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations." Eur J Biochem 153(1);13-28. PMID: 4065146

Kikonyogo96: Kikonyogo A, Pietruszko R (1996). "Aldehyde dehydrogenase from adult human brain that dehydrogenates gamma-aminobutyraldehyde: purification, characterization, cloning and distribution." Biochem J 316 ( Pt 1);317-24. PMID: 8645224

Kurys89: Kurys G, Ambroziak W, Pietruszko R (1989). "Human aldehyde dehydrogenase. Purification and characterization of a third isozyme with low Km for gamma-aminobutyraldehyde." J Biol Chem 264(8);4715-21. PMID: 2925663

Kurys93: Kurys G, Shah PC, Kikonygo A, Reed D, Ambroziak W, Pietruszko R (1993). "Human aldehyde dehydrogenase. cDNA cloning and primary structure of the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde." Eur J Biochem 218(2);311-20. PMID: 8269919

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

Lin96: Lin SW, Chen JC, Hsu LC, Hsieh CL, Yoshida A (1996). "Human gamma-aminobutyraldehyde dehydrogenase (ALDH9): cDNA sequence, genomic organization, polymorphism, chromosomal localization, and tissue expression." Genomics 34(3);376-80. PMID: 8786138

Lloyd07: Lloyd MD, Boardman KD, Smith A, van den Brink DM, Wanders RJ, Threadgill MD (2007). "Characterisation of recombinant human fatty aldehyde dehydrogenase: implications for Sjogren-Larsson syndrome." J Enzyme Inhib Med Chem 22(5);584-90. PMID: 18035827

McPherson94: McPherson JD, Wasmuth JJ, Kurys G, Pietruszko R (1994). "Human aldehyde dehydrogenase: chromosomal assignment of the gene for the isozyme that metabolizes gamma-aminobutyraldehyde." Hum Genet 93(2);211-2. PMID: 8112751

Nakahara12: Nakahara K, Ohkuni A, Kitamura T, Abe K, Naganuma T, Ohno Y, Zoeller RA, Kihara A (2012). "The Sjogren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of the sphingosine 1-phosphate degradation pathway." Mol Cell 46(4);461-71. PMID: 22633490

Ni99: Ni L, Zhou J, Hurley TD, Weiner H (1999). "Human liver mitochondrial aldehyde dehydrogenase: three-dimensional structure and the restoration of solubility and activity of chimeric forms." Protein Sci 8(12);2784-90. PMID: 10631996

Showing only 20 references. To show more, press the button "Show all references".

Report Errors or Provide Feedback
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 Thu May 5, 2016, biocyc14.