Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat

Abstract

The contribution of cystathionine gamma-lyase, cystathionine beta-synthase and cysteine aminotransferase coupled to 3-mercaptopyruvate sulphurtransferase to cysteine desulphhydration in rat liver and kidney was assessed with four different assay systems. Cystathionine gamma-lyase and cystathionine beta-synthase were active when homogenates were incubated with 280 mM-L-cysteine and 3 mM-pyridoxal 5'-phosphate at pH 7.8. Cysteine aminotransferase in combination with 3-mercaptopyruvate sulphurtransferase catalysed essentially all of the H2S production from cysteine at pH 9.7 with 160 mM-L-cysteine, 2 mM-pyridoxal 5'-phosphate, 3 mM-2-oxoglutarate and 3 mM-dithiothreitol. At more-physiological concentrations of cysteine (2 mM) cystathionine gamma-lyase and cystathionine beta-synthase both appeared to be active in cysteine desulphhydration, whereas the aminotransferase pathway did not. The effect of inhibition of cystathionine gamma-lyase by a suicide inactivator, propargylglycine, in the intact rat was also investigated; there was no significant effect of propargylglycine administration on the urinary excretion of total 35S, 35SO4(2-) or [35S]taurine formed from labelled dietary cysteine.

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

“…Both cystathionine ␥-lyase and cystathionine ␤-synthase are expressed in the kidney (7,43). Following release, hydrogen sulfide can be stored in cells as bound sulfane sulfur that can be released by reducing conditions (44).…”

“…The role of hydrogen sulfide in renal physiology and disease is beginning to be explored. Biochemical analysis has shown that the kidney produces hydrogen sulfide catalyzed by three enzymes: cystathionine ␥-lyase, cystathionine ␤-synthase, and 3-mercap-topyruvate sulfotransferase (7). Hydrogen sulfide content is decreased in the renal parenchyma in rats with streptozotocininduced diabetes, and administration of NaHS inhibited increases in TGF␤1, reactive oxygen species, and type IV collagen in diabetic rats (8).…”

H2S Biogenesis by Human Cystathionine γ-Lyase Leads to the Novel Sulfur Metabolites Lanthionine and Homolanthionine and Is Responsive to the Grade of Hyperhomocysteinemia

“…The role of H 2 S in inflammation is suggested by several studies (8 -11); however, the underlying mechanism is unknown. Remarkably, H 2 S can also induce a state of suspended animation in mice by decreasing the metabolic rate and the core body temperature presumably by inhibiting cytochrome c oxidase in the respiratory chain (12).Endogenous H 2 S is presumed to be generated primarily by desulfhydration of cysteine catalyzed by the two pyridoxal phosphate (PLP) 3 -dependent enzymes in the transsulfuration pathway: cystathionine ␤-synthase (CBS) and cystathionine ␥-lyase (CSE) (13,14). In fact, it is widely assumed, based on the reported absences of CSE in the brain (15) and of H 2 S in the brain of CBS knock-out mice (16), that CBS is the primary source of H 2 S in this organ, whereas CSE plays the equivalent role in the peripheral vasculature (3).…”

Regulation of cardiovascular cell function by hydrogen sulfide (H2S)

“…31 This implies that H 2 S deficiency might be related to pulmonary vasoconstriction and intimal thickening which are pathological factors associated with pulmonary hypertension. 11 In rats, the NOS inhibitor L-NAME produced a time-dependent elevation in systolic blood pressure associated with inhibition of CSE gene expression and H 2 S production whereas exogenous H 2 S administration prevented the development of hypertension induced by L-NAME. 32 There is also the possibility that excessive levels of H 2 S could contribute to hypotension associated with either sepsis or endotoxemia.…”