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 → Aldehyde Degradation|
|Detoxification → Methylglyoxal Detoxification|
Expected Taxonomic Range: Mammalia
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
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
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
De96a: 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
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
Lin96a: 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
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