Disease relevance of Cth

• The ability of both purified L-cysteine desulfhydrase and gamma-cystathionase to inhibit the growth of the L-cystine-dependent L1210 leukemia in culture is presented, as well as approaches to circumvent the limitations of these enzymes for in vivo therapy [1].

High impact information on Cth

• Both Cys-3 and Cys-5 were apparent sites of palmitoylation in Lck expressed in fibroblasts, as only the simultaneous mutation of both Cys-3 and Cys-5 caused a large reduction in the incorporation of [3H]palmitic acid [2].
• To study the importance of the palmitoylation of the Src-like tyrosine protein kinase p56lck in the function of the protein, Cys-3, Cys-5, or both were mutated to serine, and the mutant proteins were expressed stably in fibroblasts and T cells [2].
• RNA levels of cystathionase (cystathionine gamma-lyase), a key enzyme in the synthesis of cysteine from methionine, are elevated approximately 3.5-fold [3].
• In adult brain slices, approximately 40% of the glutathione was depleted within 10 h following gamma-cystathionase inhibition [4].
• Cystathionine beta-synthase and cystathionine gamma-lyase, both of which can produce H(2)S, were expressed in mouse pancreatic islet cells and the beta-cell line, MIN6. l-Cysteine and the H(2)S donor NaHS inhibited glucose-induced insulin release from islets and MIN6 cells [5].

Biological context of Cth

• Murine cystathionine gamma-lyase: complete cDNA and genomic sequences, promoter activity, tissue distribution and developmental expression [6].
• Thus, cystathionine gamma-lyase itself is susceptible to inactivation by oxidative stress and this can potentially exacerbate oxidant-induced damage [7].
• In the present study, we have examined the role of cystathionine gamma-lyase in maintaining the redox homeostasis in brain, particularly with reference to mitochondrial function since the complex I of the electron transport chain is sensitive to redox perturbation [7].
• These peptides were significantly identical to the partial amino acid sequences of cystathionine gamma-lyase [8].
• When mice were treated with either toxic doses of l-SeMet or a Se-deficient diet, the cystathionine gamma-lyase activity for l-SeMet was invariable, suggesting that this enzyme was effective in both detoxification and biotransformation of Se [9].

Anatomical context of Cth

• We conclude that Cys1 and Cys3 are not absolutely necessary for membrane binding or plasma membrane localization [10].
• Syndet C1S/C3S, with substitutions at the pair Cys1 and Cys3, distributes to the plasma membrane, a Golgi-like compartment, and the cytosol [10].
• It is concentrated in neuronal growth cones and associates with membranes through the palmitoylation of the N-terminal peptide MLCCMRRTK at Cys-3 and Cys-4 [11].
• Wild-type neuromodulin expressed in COS-7 cells incorporated [3H]palmitic acid, whereas a mutant in which both Cys-3 and Cys-4 were substituted with glycine was not palmitoylated in vivo [11].

Associations of Cth with chemical compounds

• Cystathionine gamma-lyase (CSE) is the last key enzyme in the trans-sulphuration pathway for biosynthesis of cysteine from methionine [6].
• Endogenous hydrogen sulfide (H(2)S) is naturally synthesized in various types of mammalian cells from l-cysteine in a reaction catalyzed by two enzymes, cystathionine-gamma-lyase (CSE) and/or cystathionine-beta-synthase [12].
• Palmitoylation of either Cys-3 or Cys-5 is required for the biological activity of the Lck tyrosine protein kinase [2].
• Many of the anticipated hIL-7 tryptic fragments were detected including one with a molecular mass equivalent to the sum of two polypeptides linked through a disulfide bond formed from Cys residues (Cys3 and Cys142) [13].
• Using radioactive fatty acids, we show herein that NOS2 becomes thioacylated at Cys-3 with palmitic acid [14].

Other interactions of Cth

• Cystationine did not influence sulfane sulfur level and rhodanese and gamma-cystathionase activity in the livers of EAT-bearing mice [15].
• Cystathionine gamma-lyase contributes to selenomethionine detoxification and cytosolic glutathione peroxidase biosynthesis in mouse liver [9].

Analytical, diagnostic and therapeutic context of Cth

• The mice were given intraperitoneal injections of 10 micro mol/kg cisplatin and subcutaneous injections of 1000 micro mol/kg propargylglycine, an inhibitor of gamma-cystathionase, once a day for 10 consecutive days from day 11 to day 20 [16].

References