Measurement of xenobiotic carbonyl reduction in human liver fractions.

Carbonyl reducing enzymes are involved in the metabolism of endogenous as well as xenobiotic molecules. Enzymes that catalyze the reversible oxidoreduction of aldehyde and ketone moieties include alcohol dehydrogenases, aldo-keto reductases, quinone reductases, and short-chain dehydrogenases/reductases. These enzymes differ with respect to subcellular location, cofactor dependence, and susceptibility to chemical inhibitors.

Human carbonyl reduction pathways and a strategy for their study in vitro.

Carbonyl reduction plays a significant role in physiological processes throughout the body. Although much is known about endogenous carbonyl metabolism, much less is known about the roles of carbonyl-reducing enzymes in xenobiotic metabolism. Multiple pathways exist in humans for metabolizing carbonyl moieties of xenobiotics to their corresponding alcohols, readying these molecules for subsequent conjugation and/or excretion.

Enzymology of a carbonyl reduction clearance pathway for the HIV integrase inhibitor, S-1360: role of human liver cytosolic aldo-keto reductases.

S-1360, a 1,3-diketone derivative, was the first HIV integrase inhibitor to enter human trials. Clinical data suggested involvement of non-cytochrome P450 clearance pathways, including reduction and glucuronidation. Reduction of S-1360 generates a key metabolite in humans, designated HP1, and constitutes a major clearance pathway.

Dieldrin stimulates biliary excretion of 14C-benzo[a]pyrene polar metabolites but does not change the biliary metabolite profile in rainbow trout (Oncorhyncus mykiss).

Activities of hepatic microsomal and cytosolic epoxide hydrolases, accumulation of dieldrin in liver, and in vivo metabolism and disposition of the polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BP), were examined in rainbow trout pretreated with dieldrin, a chlorinated cyclodiene insecticide. Rainbow trout were fed 0.3 mg dieldrin/kg/day for 9 weeks and the same dose of dieldrin for 9 weeks, followed by 3 weeks on control diet (12 weeks).

Ability of MBP or RBP signal peptides to influence folding and in vitro translocation of wild-type and hybrid precursors.

Maltose-binding protein (MBP), whose export in E. coli is dependent upon the chaperone SecB, and ribose-binding protein (RBP), whose export is SecB-independent, have been used to generate hybrid secretory proteins. Here, in vitro techniques were used to analyze MBP, RBP, RBP-MBP (RBP signal and MBP mature), and MBP-RBP (MBP signal and RBP mature).