Relationship between glutathione content in liver and glutathione conjugation rate in the rat in vivo. Effect of buthionine sulphoximine pretreatment on conjugation of the two 2-bromoisovalerylurea enantiomers during intravenous infusion

Abstract

The relationship between hepatic glutathione content and hepatic glutathione conjugation rate in the rat in vivo was investigated. As substrate for glutathione conjugation, racemic (R,S)-2-bromoisovalerylurea (BIU) was used which gives rise to the biliary excretion of two diastereoisomeric glutathione conjugates and the urinary excretion of two diastereoisomeric mercapturates. The excretion rate of the glutathione conjugate in bile reflects hepatic conjugation exclusively. An intravenous infusion of BIU was given and the excretion rates of the metabolites in bile and urine were determined. The glutathione concentration in the liver was followed by taking biopsies every hour. Glutathione was depleted by the infused substrate; in rats that were pretreated with the inhibitor of glutathione biosynthesis, buthionine sulphoximine (BSO), the depletion of the glutathione content was more rapid. The rate of excretion of the glutathione conjugate in bile was plotted against hepatic glutathione content. These results indicate that the 'organ Km' for glutathione in the liver is approximately 0.5 mumol/g of liver, so that the hepatic glutathione conjugation rate is decreased only at severe glutathione depletion.

Modification of microsomal 11β-HSD1 activity by cytosolic compounds: Glutathione and hexose phosphoesters

“…Because of the ease by which they are oxidized, mammalian cells sustain millimolar concentrations of these protective non-protein sulhydryls. In rat liver microsomes, and using glutathione concentrations thought to exist in the canine pancreatic ER (i.e., up to and well exceeding 1.0 mM) [47] and liver [25,52,53], GSSG, and GSH to a marginal degree, were found in our study to alter liver microsomal 11␤-HSD1 reductase. Coordinate opposing actions of GSSG and H 2 O 2 on the 11␤-HSD1 dehydrogenase (Fig.…”

A -Glutamyl Cyclotransferase Protects Arabidopsis Plants from Heavy Metal Toxicity by Recycling Glutamate to Maintain Glutathione Homeostasis

“…The detoxification of heavy metals by GSH conjugation results in the rapid depletion of GSH in the cytoplasm (Polhuijs et al, 1992). Under these conditions, GSH homeostasis is maintained by the g-glutamyl cycle (Figure 1), which involves GSH synthesis and degradation, and the recycling of the component amino acids Glu, Cys, and Gly (Griffith et al, 1978).…”

Protection against 3,4‐methylenedioxymethamphetamine‐induced neurodegeneration produced by glutathione depletion in rats is mediated by attenuation of hyperthermia

“…Previous studies, however, have shown that a high degree of GSH depletion is required to have any effect on the rate of substrate conjugation (Mulder and Ouwerkerk‐Mahadevan 1997). Indeed, according to Polhuijs et al . (1992) hepatic levels of GSH must be reduced to below 1 µmol/g tissue before significantly affecting the conjugation rate.…”