Disease relevance of D-lactoylglutathione

• The mechanism of E. coli Ni-GlxI was investigated by analyzing Ni K-edge X-ray absorption spectroscopic (XAS) data obtained from the enzyme and complexes formed with the product, S-D-lactoylglutathione, and various inhibitors [1].
• S-2-Hydroxyacylglutathione derivatives also inhibited the incorporation of [3H]thymidine into DNA early in the development of toxicity: for S-D-lactoylglutathione, the median inhibitory concentration was 74 microM (95% C.I. 47-116 microM) [2].
• The assay of S-D-lactoylglutathione is of increasing interest in studies of the elevation of glyoxalase metabolites in diabetes mellitus and in investigations of the antiproliferative activity of S-D-lactoylglutathione [3].
• In addition, glyoxalase II activity decrease in the adenocarcinoma tissue suggests a likely role of the intermediate S-D-lactoylglutathione by supplying energy in actively proliferating cells [4].

High impact information on D-lactoylglutathione

• Glyoxalase-I catalyzes the conversion of MG to S-D-lactoylglutathione, which in turn is converted to D-lactate by glyoxalase-II [5].
• For human erythrocyte Glx I, catalysis is unlikely to be coupled to major changes in protein secondary structure, as the circular dichroism spectrum of the enzyme (190-260 nm) is insensitive to saturating concentrations of either enediol analog or S-D-lactoylglutathione, the product of the Glx I reaction [6].
• The structure of the active site of human glyoxalase I and the reaction mechanism of the enzyme-catalyzed conversion of the thiohemiacetal, formed from methylglyoxal and glutathione, to S-D-lactoylglutathione has been investigated by ab initio quantum chemical calculations [7].
• When sucrose is used as a viscogenic agent, kcat/Km for S-D-lactoylglutathione (8.8 x 10(5) M-1 s-1) decreases markedly with increasing solution viscosity [8].
• Glyoxalase II from rat erythrocytes is a near optimal catalyst for the hydrolysis of S-D-lactoylglutathione in the sense that the magnitude of kcat/Km is limited, in large part, by the rate constant for diffusion-controlled encounter between substrate and active site [8].

Chemical compound and disease context of D-lactoylglutathione

• E. coli C600 cells transformed with GLO I gene of P. putida showed a high GLO I activity and were used for the preparation of S-D-lactoylglutathione and other glutathione thiol esters [9].

Biological context of D-lactoylglutathione

• The mechanism of the inhibition of human leukaemia cell growth by S-D-lactoylglutathione and other S-2-hydroxyacylglutathione derivatives is unknown but appears to be mediated by the inhibition of DNA synthesis [2].
• S-D-Lactoylglutathione was the most effective with a median inhibitory concentration IC50 of 82 microM (95% C.I. 65-105 microM) [2].
• The determination of glyoxalase II (S-(2-hydroxyacyl)glutathione hydrolase, EC 3.1.2.6) activity is usually accomplished by monitoring the decrease of absorbance at 240 nm due to the hydrolysis of S-d-lactoylglutathione [10].
• Glyoxalase I is a ubiquitous enzyme that catalyzes the conversion of methylglyoxal, a toxic 2-oxoaldehyde derived from glycolysis, to S-D-lactoylglutathione [11].
• Using this method we characterized the kinetics of glyoxalase II in situ using S-d-lactoylglutathione as substrate and compared the results with those obtained for cell-free extracts [10].

Anatomical context of D-lactoylglutathione

• The corrected values for the reverse reaction catalyzed by glyoxalase I from human erythrocytes with S-D-lactoylglutathione as substrate were kcat = 3.6 s-1 and Km = 1.9 mM [12].
• This modification may be related to the ability of S-D-lactoylglutathione to stimulate the assembly of microtubules [13].
• S-D-lactoylglutathione in resting and activated human neutrophils [13].
• Human promyelocytic leukaemia HL60 cells were incubated with the glyoxalase intermediate S-D-lactoylglutathione in culture [14].
• The mechanism of inhibition of proliferation of HL60 promyelocytes by S-D-lactoylglutathione is unknown but it may be related to the ability of S-D-lactoylglutathione to stimulate the assembly of microtubules [14].

Associations of D-lactoylglutathione with other chemical compounds

• Glyoxalase (GLO) II, which is a component of GLO system and catalyze the conversion of S-lactoyl-glutathione to D-lactate, was purified 1488 fold from rat liver by two steps of Affigel blue and carbobenzoxyglutathione-Sepharose 4B affinity chromatography [15].
• The concentrations of UTP, CTP, UDP and also ATP, ADP, GTP and GDP decreased in S-D-lactoylglutathione-treated HL60 cells, whereas the concentration of UDP-N-acetylhexosamine (UDP-N-acetyl-glucosamine + N-acetyl-galactosamine) increased, prior to cell death [16].

Gene context of D-lactoylglutathione

• The enzymes produced in minimal media were active towards the substrate S-D-lactoylglutathione, yielding kcat/ Km values similar to those of rich media GLX2-2 [17].
• Glyoxalase-I (S-lactoyl-glutathione methylglyoxal-lyase (isomerizing), EC 4.4.1.5) was purified from rat liver, erythrocytes, brain and kidney using two different purification procedures [18].
• Glyoxalase-I (Gly-I) is part of the glyoxalase system which converts methylglyoxal to D-lactic acid via an S-D-lactoylglutathione intermediate [19].

Analytical, diagnostic and therapeutic context of D-lactoylglutathione

• Determination of rat blood S-D-lactoylglutathione by a column-switching high-performance liquid chromatography with precolumn fluorescence derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole [20].
• S-D-Lactoylglutathione was assayed by reverse-phase high-performance liquid chromatography (HPLC) with spectrophotometric detection of the thiolester chromophore at 233 nm [3].

References