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.
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Review Article|
June 13 2013
The glyoxalase pathway: the first hundred years… and beyond
Marta Sousa Silva;
Marta Sousa Silva
1
1Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Portugal
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Ricardo A. Gomes;
Ricardo A. Gomes
1
1Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Portugal
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Antonio E. N. Ferreira;
Antonio E. N. Ferreira
1Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Portugal
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Ana Ponces Freire;
Ana Ponces Freire
1Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Portugal
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Carlos Cordeiro
Carlos Cordeiro
2
1Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Portugal
2To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
November 19 2012
Revision Received:
March 05 2013
Accepted:
March 05 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 453 (1): 1–15.
Article history
Received:
November 19 2012
Revision Received:
March 05 2013
Accepted:
March 05 2013
Citation
Marta Sousa Silva, Ricardo A. Gomes, Antonio E. N. Ferreira, Ana Ponces Freire, Carlos Cordeiro; The glyoxalase pathway: the first hundred years… and beyond. Biochem J 1 July 2013; 453 (1): 1–15. doi: https://doi.org/10.1042/BJ20121743
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