title: Activity, regulation, copy number and function in the glyoxalase system.
abstract: Molecular, catalytic and structural properties of glyoxalase pathway enzymes of many species are now known. Current research has focused on the regulation of activity and expression of Glo1 (glyoxalase I) and Glo2 (glyoxalase II) and their role in health and disease. Human GLO1 has MRE (metal-response element), IRE (insulin-response element), E2F4 (early gene 2 factor isoform 4), AP-2α (activating enhancer-binding protein 2α) and ARE (antioxidant response-element) regulatory elements and is a hotspot for copy number variation. The human Glo2 gene, HAGH (hydroxyacylglutathione hydrolase), has a regulatory p53-response element. Glo1 is linked to healthy aging, obesity, diabetes and diabetic complications, chronic renal disease, cardiovascular disease, other disorders and multidrug resistance in cancer chemotherapy. Mathematical modelling of the glyoxalase pathway predicts that pharmacological levels of increased Glo1 activity markedly decrease cellular methylglyoxal and related glycation, and pharmacological Glo1 inhibition markedly increases cellular methylglyoxal and related glycation. Glo1 inducers are in development to sustain healthy aging and for treatment of vascular complications of diabetes and other disorders, and cell-permeant Glo1 inhibitors are in development for treatment of multidrug-resistant tumours, malaria and potentially pathogenic bacteria and fungi.
authors.affiliation: *Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry CV2 2DX, U.K.
authors.forename: Naila
authors.initials: N
authors.lastname: Rabbani
authors.affiliation: *Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry CV2 2DX, U.K.
authors.forename: Mingzhan
authors.initials: M
authors.lastname: Xue
authors.affiliation: *Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry CV2 2DX, U.K.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thornalley
mesh_terms: D000818:Animals; D056915:DNA Copy Number Variations / Q000235:genetics*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000235:genetics* / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology / Q000235:genetics; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D007791:Lactoylglutathione Lyase; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase