title: The glyoxalase pathway: the first hundred years... and beyond.
abstract: The discovery of the enzymatic formation of lactic acid from methylglyoxal dates back to 1913 and was believed to be associated with one enzyme termed ketonaldehydemutase or glyoxalase, the latter designation prevailed. However, in 1951 it was shown that two enzymes were needed and that glutathione was the required catalytic co-factor. The concept of a metabolic pathway defined by two enzymes emerged at this time. Its association to detoxification and anti-glycation defence are its presently accepted roles, since methylglyoxal exerts irreversible effects on protein structure and function, associated with misfolding. This functional defence role has been the rationale behind the possible use of the glyoxalase pathway as a therapeutic target, since its inhibition might lead to an increased methylglyoxal concentration and cellular damage. However, metabolic pathway analysis showed that glyoxalase effects on methylglyoxal concentration are likely to be negligible and several organisms, from mammals to yeast and protozoan parasites, show no phenotype in the absence of one or both glyoxalase enzymes. The aim of the present review is to show the evolution of thought regarding the glyoxalase pathway since its discovery 100 years ago, the current knowledge on the glyoxalase enzymes and their recognized role in the control of glycation processes.
authors.affiliation: Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Sousa Silva
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Gomes
authors.forename: Antonio E N
authors.initials: AE
authors.lastname: Ferreira
authors.forename: Ana
authors.initials: A
authors.lastname: Ponces Freire
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordeiro
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D019757:Carbon-Oxygen Lyases / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000378:metabolism*; D013869:Thiolester Hydrolases / Q000378:metabolism*; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D000445:Aldehyde Oxidoreductases; D019757:Carbon-Oxygen Lyases; D005978:Glutathione; D017127:Glycation End Products, Advanced; D007791:Lactoylglutathione Lyase; D011765:Pyruvaldehyde; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase; C091855:glyoxalase III; C021578:methylglyoxal synthase