Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.2.3 (glutathione synthetase)
 678 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structural gene for glyoxalase I (GLO1) of Saccharomyces cerevisiae was identified. The GLO1 gene contained an open reading frame with 326 amino acids, and the molecular weight of the gene product (Glo1p) deduced from the DNA sequence was calculated to be 37,207.06. Glyoxalase I activity increased approximately 95-fold when the GLO1 gene was introduced into the yeast cell with a multicopy plasmid, and the resultant transformant showed the increased resistance against methylglyoxal. Since the knockout mutant of the GLO1 gene of haploid strain of S. cerevisiae was still viable, the GLO1 gene was thought to be unnecessary for growth of the yeast. The GLO1 gene was overexpressed in two kinds of glutathione-deficient mutants, gamma-glutamylcysteine synthetase-deficient (gsh1(-)) and glutathione synthetase-deficient (gsh2(-)), respectively, and the sensitivites to methylglyoxal were compared. The gsh1-deficient mutant, which could not produce glutathione at all, was hypersensitive to methylglyoxal, and overproduction of the Glo1p did not restore the growth arrest caused by exogenously added methylglyoxal. The gsh2-deficient mutant, which accumulates gamma-glutamylcysteine (an intermediate of glutathione biosynthesis), was also sensitive to methylglyoxal compared with the isogenic wild type strain, although the growth arrest caused by methylglyoxal was partially restored by overexpression of the GLO1 gene. Purified glyoxalase I from yeast could use gamma-glutamylcysteine as a substrate (kcat/Km = 1.89 x 10(7) M-1 s-1, glutathione; 3.47 x 10(4) M-1 s-1, gamma-glutamylcysteine).
 ...
PMID:Identification of the structural gene for glyoxalase I from Saccharomyces cerevisiae. 882 31

Saccharomyces cerevisiae is an outstanding cellular model for metabolic studies in glycation. Due to its high glycolytic activity, it produces methylglyoxal, a highly reactive intracellular glycation agent, at a rate of approx. 0.1% of the glycolytic flux. We investigated methylglyoxal metabolism in Saccharomyces cerevisiae cells, using haploid null mutants. Growth studies showed that the most sensitive strains to 2-oxoaldehydes were the null mutants for GSH1 and GLO1, coding for glutathione synthase I and glyoxalase I respectively. The GRE3 null mutant, lacking aldose reductase activity, is as sensitive as the control strain. Kinetic modelling and computer simulation of this type of experiment were also performed, and we concluded that the most important parameters for controlling the intracellular concentration of methylglyoxal are the activity of glyoxalase I and the GSH concentration. Moreover, our model predicts an intracellular steady-state concentration of methylglyoxal of approx. 2 microM. Our results show that the glyoxalase pathway is the main detoxification pathway for 2-oxoaldehydes in yeast, and is likely to be the key enzymatic anti-glycation agent in these cells.
 ...
PMID:Anti-glycation defences in yeast. 1464 Oct 76