Detoxification reactions, sulfur amino

Cysteine is considered a nonessential nutrient because it can be synthesized from methionine via the transsulfuration pathway (Figs. 21-1 and 21-2). Production of cysteine is metabolically important because it serves as a source of sulfur for incorporation into proteins and detoxification reactions. A lack of cysteine needed for incorporation into the structural protein collagen may be responsible for the musculoskeletal abnormalities seen in patients with CBS deficiency. A major metabolic use of cysteine is in the production of glutathionine (y-glutamylcysteinylglycine), an important antioxidant. Another important pathway for cysteine metabolism is its oxidation to cysteinesulfinate, which serves as a precursor for taurine, an amino acid that stabilizes cell membranes in the brain. 

Reactions between the sulfur-containing amino acids cysteine and methionine (Fig. 2.18) and rufhenium(II) arene anticancer complexes are of much interest in view of the strong influence of sulfur amino acids on the intracellular chemistry of platinum drugs, their involvement in detoxification and resistance mechanisms [100]. We found [101] that [(ri -biphenyl)Ru(en)Cl][PF 5] reacts slowly with the thiol amino add L-cysteine in aqueous solution at 310 K, pH 2-5, and only to about 50% completion at a 1 2 mM ratio. Reactions appeared to involve aquation as the first step followed by initial formation of 1 1 adducts via substitution of water by S-bound or O-bound cysteine. Two dinuclear complexes were also detected as products from the reaction. In these reactions half or all of the chelated ethylene-diamine had been displaced and one or two bridging cysteines were present The unusual cluster species (biphenyl) Ru g was also formed espedaUy at higher cysteine concentrations. The reaction was suppressed in 50 mM triethylammo-nium acetate solution at pH > 5 or in 100 mM NaCl suggesting that thiols may not readily inactivate Ru(II)-en arene complexes in blood plasma or in cells. Similarly, reactions with the thioether sulfur of methionine appeared to be relatively weak. Only 27% of [(r -biphenyl)Ru(en)Cl][PF5] reacted with L-methionine (L-MetH) at an initial pH of 5.7 after 48 h at 310 K, and gave rise to only one adduct [(ri -biphenyl) Ru(en) (i-MetH -S)]. ... 

A third sulfurtransferase, cystathionase (cystathionine y-lyase EC 4.4.1.1), which is a cytosohc enzyme, may play a role in CN detoxification in the kidney and rhombencephalon (Wrobel et al., 2004). A product of the cystathionase reaction, bis(2-amino-2-carboxylethyl)trisulfide (thiocystine), may serve as a sulfur substrate donor for rhodanese. Another reaction product, 3-(thiosulpheno)-alanine (thiocysteine), may be an additional link between cystathionase and CN biodetoxification. In addition, cystathionase also functions as a sulfane sulfur carrier. 

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