Disease relevance of L-Cysteinylglycine

• Here, we show that the kissing bug Rhodnius prolixus, a vector of Chagas' disease, has a unique heme-degradation pathway wherein heme is first modified by addition of two cysteinylglycine residues before cleavage of the porphyrin ring, followed by trimming of the dipeptides [1].
• We determined reduced, oxidized, and protein-bound homocysteine, cysteine, and cysteinylglycine in plasma from 13 patients with hyperhomocysteinemia (total homocysteine in the range 30.6-159.8 mumol/L) due to cobalamin deficiency [2].
• Aminopeptidases A, B, and N and dipeptidase D, with broad substrate specificity, are the four cysteinylglycinases of Escherichia coli K-12, and there is no peptidase specific for the cleavage of cysteinylglycine [3].
• The ratios of free to oxidized cysteinylglycine and glutathione were higher in women with HELLP syndrome than in those with preeclampsia (5.4 [3.3-12.7] versus 4.1 [2.3-11.6], P =.02, and 56 [28-124] versus 45 [16-166], P =.02, respectively) [4].
• We recently studied the utilization of glutathione (L-gamma-glutamyl-L-cysteinylglycine), L-cysteinylglycine and L-cysteine by anaerobic bacteria [5].

High impact information on L-Cysteinylglycine

• The presence of L-cysteinylglycine S-acetyldextran polymer (Mr 500,000), which does not permeate membranes, protected the membrane-bound transferase from inactivation by 6-diazo-5-oxo-L-norleucyglycine [6].
• GGT-deficient mice have markedly reduced levels of glutathione (GSH), cysteine, methionine, and cysteinylglycine in liver [7].
• These results suggest that GSH which is secreted into the tubular lumen by a specific translocase in the lumenal membranes or filtered by the glomerulus may be degraded in situ by membranous gamma-glutamyltransferase and peptidase activities which hydrolyze peptide bonds of cysteinylglycine and its derivatives [8].
• Glycine and taurine conjugates of bile acids modulate gamma-glutamyl transpeptidase by interacting with the cysteinylglycine binding site (acceptor site) of the enzyme [9].
• Renal catabolism of glutathione. Characterization of a particulate rat renal dipeptidase that catalyzes the hydrolysis of cysteinylglycine [10].

Chemical compound and disease context of L-Cysteinylglycine

• CONCLUSION: Significantly lower ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine in preeclampsia might indicate oxidative stress [4].
• Methionine was decreased and cysteinylglycine was increased in patients with chronic renal failure [11].

Biological context of L-Cysteinylglycine

• This is consistent with a model of an indirect mechanism of mutagenesis, i.e. cleavage of GSH by GGT, followed by facile auto-oxidation of the resulting cysteinylglycine, with the production of free radicals which lead to the (pen)ultimate mutagen, H2O2 [12].
• Furthermore, neither oxothiazolidine-4-carboxylate (OTC), a cellular cysteine-delivery compound, nor cysteinylglycine, a dipeptide released from the gamma-GT reaction, stimulated cell proliferation [13].
• These metabolites result from partial acetylation or acetylation/deacetylation of cysteine or cysteinylglycine adducts [14].
• Glutathione precursors (cysteine, cysteinylglycine, glutamylcysteine and homocysteine) and products of lipid peroxidation (thiobarbituric acid-reactive substances) were also measured in plasma and did not differ between healthy control subjects and HIV-seropositive individuals [15].
• RPT cell monolayers metabolise MGNQ into a cysteinylglycine conjugate, which after intramolecular cyclization yields 2H-(3-glycinyl)-9-hydroxy-10-methyl-1,4-naphthothiazine [16].

Anatomical context of L-Cysteinylglycine

• The present study demonstrates for the first time that an established cell line expressing GGT-rel, a human GGT-related enzyme, metabolizes extracellular GSH to cysteinylglycine (CysGly) in a time-dependent manner when cells were incubated in a medium containing 2.5 mM GSH and 25 mM glycylglycine [17].
• Bile and pancreatic juice collected from normal rats metabolized glutathione conjugates of 1-NP oxides and produced the corresponding cysteinylglycine and cysteine conjugates [18].
• The major part (over 95%) of total hepatic cysteinylglycine S-conjugate dipeptidase activity was located in the cytosol [19].
• In studies on human erythrocyte metabolism in situ, high resolution (400 MHz) 1H spin-echo NMR spectroscopy was used to follow the time dependence of hydrolysis of glycylglycine and L-cysteinylglycine in intact cells and their lysates [20].
• METHODS: In 156 couples undergoing assisted reproduction techniques (ART), we measured the concentrations of glutathione (GSH), cysteine (Cys), homocysteine (Hcy) and cysteinylglycine (CGS) and fertility outcome parameters in the ejaculate, purified spermatozoa and follicular fluid [21].

Associations of L-Cysteinylglycine with other chemical compounds

• Modulation of the hydrolysis, transfer, and glutaminase activities of gamma-glutamyl transpeptidase by maleate bound at the cysteinylglycine binding site of the enzyme [22].
• The ratio of reduced homocysteine to total homocysteine was positively correlated with the reduced-total ratio for cysteine and cysteinylglycine, suggesting redox equilibrium between different aminothiol species [2].
• METHODS: We used capillary electrophoresis to measure LDL-bound thiols [homocysteine, cysteine (Cys), cysteinylglycine, glutathione, and glutamylcysteine] in 104 healthy study participants We also assessed total plasma thiol concentrations and lipid profiles [23].
• The data suggest that cytosolic cysteinylglycine S-conjugate dipeptidase as identified here is involved in hepatic mercapturic acid formation from sinusoidal cysteinylglycine S-conjugates [19].
• Glutathione, cysteinylglycine, cysteine, and their disulfides were measured by high-performance liquid chromatography [24].

Gene context of L-Cysteinylglycine

• Besides, the extracellular cleavage of GSH by GGT leads to reactive oxygen species (ROS) production, depending on the generation and enhanced reactivity of cysteinylglycine (CysGly) [25].
• The effectiveness of cysteine and cysteinylglycine to act as protein thiolating agents was investigated using bovine lens aldose reductase (ALR2) as the protein target [26].
• We further confirmed the hypothesis that cysteinylglycine (CysGly), a product of GGT/GSH reaction, identified by high-performance liquid chromatography, but not GSH, was responsible for ROS formation initiated by the reductive release of iron from transferrin [27].
• In kidneys, the ectopeptidase aminopeptidase N (ApN) has been reported to hydrolyze CysGly [28].
• The data presented support the hypothesis that the nephrotoxicity of chlorotrifluoroethene is due to the enzymatic formation of a glutathione conjugate, which is metabolized to the ultimate nephrotoxin by the sequential action of renal gamma-glutamyltransferase, cysteinylglycine dipeptidase and cysteine conjugate beta-lyase [29].
• Yeast cells lacking Dug1p (dug1Delta) accumulate Cys-Gly [30].

Analytical, diagnostic and therapeutic context of L-Cysteinylglycine

• HPLC analysis of biliary metabolites from rats administered [3H]1-NP orally showed the presence of glutathione conjugates of 1-NP 4,5-oxide and 1-NP 9,10-oxide and their metabolites, cysteinylglycine and cysteine conjugates [18].
• A selective and sensitive method for the determination of glutathione (GSH) and related aminothiols such as cysteine (Cys), cysteinylglycine (CysGly) and gamma-glutamylcysteine (gamma-GluCys) by gas chromatography (GC) has been developed [31].
• The levels of different fractions of homocysteine, cysteine and cysteinylglycine were investigated in 17 patients on chronic hemodialysis, 9 patients with reduced renal function and 4 patients with nephrotic syndrome and compared with 14 healthy subjects [32].
• Switching the perfusion direction also saw a significant rise in the cysteinylglycine efflux [33].
• Serum homocysteine, cysteine, cysteinylglycine and glutathione were measured in 86 patients with a diagnosis of essential hypertension and compared with those of an age- and sex-matched control group [34].

References