Interaction of γ‐glutamyl transpeptidase with S‐acyl derivatives of glutathione

The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life

“…There is usually only one phenotype expressed, although a rare second form (frequency 0.016) was found in a Micronesian population (Board, 1980). Glyoxalase II polymorphism deserves further investigation, however, since one of only two published surveys (Charlesworth, 1972) Al-Timari & Douglas, 1986 lactoylglutathione to S-D-lactoylcysteinylglycine which rearranges to N-lactoylcysteinylglycine (Tate, 1975) S-D-Lactoylglutathione induces some extraordinary and unexpected biological responses: it potentiates the GTP-promoted assembly of microtubules from porcine brain microtubular protein over the physiological concentration range (Hooper, 1988) and influences neutrophil movement and stimulus-induced secretion of granules (Thornalley, 1989). Moreover, addition of S-D-lactoylglutathione to HL60 leukaemia cells in culture induces growth arrest and toxicity (Thornalley & Tisdale, 1988).…”

Donor substrate specificity of bovine kidney gamma-glutamyltransferase

“…The catalytic cycle of GGT follows a ping-pong mechanism (Figure 4), similar to the type of enzymatic mechanism observed with serine proteases (Tate and Meister, 1974;Morin et al, 2006). One substrate binds to the enzyme and one product is released; a second substrate binds and a second product is released, resembling a ping pong ball moving back and forth.…”

“…In addition, GGT incubated with GSH alone produced a small amount of glutamate, suggesting that a hydrolysis reaction also occurs, with water as the acceptor substrate (Hanes et al, 1950, Hanes et al, 1952. The transpeptidation reaction is thought to occur when high concentrations of amino acids or dipeptides are present (Tate and Meister, 1974). In a standard assay (described in section 1.4.5) with donor substrate γ-glutamyl-p-nitroanilide (GpNA) and various acceptor substrates, the highest specific activities for rat kidney GGT were observed with glycylglycine (glygly; 110 μmol/min/mg), glutamine (37 μmol/min/mg) and methionine (35 μmol/min/mg) as acceptor substrates (Tate and Meister, 1974).…”

“…The transpeptidation reaction is thought to occur when high concentrations of amino acids or dipeptides are present (Tate and Meister, 1974). In a standard assay (described in section 1.4.5) with donor substrate γ-glutamyl-p-nitroanilide (GpNA) and various acceptor substrates, the highest specific activities for rat kidney GGT were observed with glycylglycine (glygly; 110 μmol/min/mg), glutamine (37 μmol/min/mg) and methionine (35 μmol/min/mg) as acceptor substrates (Tate and Meister, 1974). The generation of glutamate through the hydrolysis reaction is thought to be the predominant reaction occurring at physiological pH (Wickham et al, 2011).…”

“…Autotranspeptidation may occur with high concentrations of donor substrates or when no acceptor substrate is present (Tate and Meister, 1974;Morin et al, 2006;Wickham et al, 2011). …”