In human liver microsomes, triazolam is principally metabolized by CYP3A4 to form two metabolites, 1'-hydroxytriazolam (1'OHTz) and 4-hydroxytriazolam (4OHTz). The velocity of 1'OHTz formation was found to decrease at higher triazolam concentrations (>200 microM), indicative of "substrate inhibition". Coincubation of [(14)C]triazolam with authentic metabolite standards of either 1'OHTz or 4OHTz...

Manoalide, an unusual nonsteroidal sesterterpenoid recently isolated from sponge, antagonizes phorbol-induced inflammation but not that induced by arachidonic acid, suggesting that manoalide acts prior to the cyclooxygenase step in prostaglandin synthesis, possibly by inhibiting phospholipase A2. We have now studied the inhibitory effect of manoalide on a homogeneous preparation of phospholipas...

BACKGROUND Fructose-1,6-bisphosphatase, a major enzyme of gluconeogenesis, is inhibited by AMP, Fru-2,6-P2 and by high concentrations of its substrate Fru-1,6-P2. The mechanism that produces substrate inhibition continues to be obscure. METHODS Four types of experiments were used to shed light on this: (1) kinetic measurements over a very wide range of substrate concentrations, subjected to d...

Phosphoribosylpyrophosphate (PRPP) synthetase participates in the biosynthesis in bacteria of purine nucleotides, pyrimidine nucleotides, tryptophan, histidine, and the pyridine nucleotide coenzymes. A kinetic study of the interaction of highly purified PRPP synthetase from Salmonella typhimurium with end products and other potential metabolite effecters has been conducted. There is no evidence...

The substrate inhibition of palmityl coenzyme A:carnitine 0-palmityltransferase (EC 2.3.1.-) by palmityl-CoA has been studied. Beside being a substrate for the enzyme, palmityl-CoA was found to behave as a competitive inhibitor for the second substrate (carnitine). The Ki was found to be approximately 3 X 10-e M, while the K, for palmityl-CoA was found to be approximately 10M5 M. Thus, the affi...

We have identified a cDNA, PGT, that encodes a widely expressed transporter for prostaglandin (PG) E(2), PGF(2alpha), PGD(2), 8-iso-PGF(2alpha), and thromboxane B(2). To begin to understand the molecular mechanisms of transporter function, we have initiated a structure-function analysis of PGT to identify its substrate-binding region. We have found that by introducing the small, water-soluble, ...

This paper investigates and provides a critical analysis of the toluene biofilter model developed by Li and De Visscher. The model simulation results have been reproduced and compared with several sets of experimental data from literature. Three different model variations are considered: model with no substrate inhibition, with substrate inhibition, and with air flow rate modification. A sensit...

UDP-glucuronosyltransferase (UGT) 1A4-catalyzed glucuronidation is an important drug elimination pathway. Although atypical kinetic profiles (nonhyperbolic, non-Michaelis-Menten) of UGT1A4-catalyzed glucuronidation have been reported occasionally, systematic kinetic studies to explore the existence of multiple aglycone binding sites in UGT1A4 have not been conducted. To this end, two positional...

Undecaprenyl pyrophosphate synthase (UPPS) catalyzes the consecutive condensation of eight molecules of isopentenyl pyrophosphate (IPP) with farnesyl pyrophosphate (FPP) to generate the C(55) undecaprenyl pyrophosphate (UPP). It has been demonstrated that tetramic acids (TAs) are selective and potent inhibitors of UPPS, but the mode of inhibition was unclear. In this work, we used a fluorescent...

Porcine microsomes are able to hydroxylate chlorzoxazone and p-nitrophenol, the most commonly used human test substrates for CYP2E1. However, in pigs, CYP2E appears not to be the only enzyme involved in the hydroxylation of chlorzoxazone and p-nitrophenol, as the enzyme capacity and immunochemical level of the apoprotein do not correlate. The present study shows that the hydroxylation of chlorz...