Enzymes disruptions

Adverse effects of mercury on aquatic organisms, in addition to those listed on reproduction and growth, have been documented at water concentrations of 0.88 to 5.0 pg/L enzyme disruption in brook trout (Salvelinus fontinalis) embryos immersed for 17 days in solutions containing... 

The molecular target site of triketone herbicides is the enzyme -hydroxyphenylpyruvate dioxygenase (HPPD). Inhibition of this enzyme disrupts the biosynthesis of carotenoids and causes a bleaching (loss of chlorophyll) effect on the foliage similar to that observed with inhibitors ofphytoene desaturase (e.g. norflurazon). However, the mechanism of action of HPPD inhibitors is different. Inhibtion of HPPD stops the synthesis of homogen tisate (HGA), which is a key precursor of the 8 different tocochromanols (tocopherols and tocotrienols) and prenyl quinones. In the absence of prenylquinone plastoquinone, phytoene desaturase activity is interrupted. The bleaching of the green tissues ensues as if these compounds inhibited phytoene desaturase. 

In 1973 a small community in Louisiana exhibited enzyme disruptions attributed to the presence of up to 23 ppb HCB in the blood of affected inhabitants (ref. 93) ... 

Sesquiterpenes containing either a methylene-y-lactone or a cyclopentenone moiety can react with thiol groups to form a covalent linkage. If the thiol group is on a key enzyme, interaction with artemisinin could inactivate the enzyme, disrupting metabolism. Cysteine is a good antidote for artemisinin as a phytotoxin, but there is no evidence that it is due to a direct interaction of the two molecules.15... 

Binds to sulfide groups, blocking sulfhydril enzymes, disrupting cellular metabolism... 

A FRET-based reporter gene assay that is now commercially available from Panvera was described by Zlokarneik and co-workers [109]. The assay uses a membrane-permeable substrate (CCE2, a coumarin-fluorescein derivative) for the reporter protein j3-lactamase. By hydrolyzing the substrate, the enzyme disrupts the intramolecular resonance energy transfer between the coumarin and the fluorescein, which changes the fluorescence emission from green at 520 run to blue at... 

Adverse effects of mercury to fishes, in addition to those listed on reproduction and growth, have been documented at water concentrations of 0.88-5.0 xg/L enzyme disruption in brook trout (Salvelinus fontinalis) embryos immersed for 17 days in solutions containing 0.88 ig/L, as methylmercury decreased rate of intestinal transport of glucose, fructose, glycine, and tryptophan in the murrel (Channa punctatus) at 3.0 (xg Hg +/L for 30 days altered blood chemistry in striped bass (Morone saxatilis) at 5.0 xg Hg +/L in 60 days and decreased respiration in striped bass 30 days post-exposure after immersion for 30-120 days in 5.0 xg Hg +/L. In large-mouth bass, elevated liver metallothioneins are indicative of elevated muscle mercury concentrations, suggesting that mercury-induced metallothioneins may be useful biomarkers of mercury exposure. 

Herbicidal sulfonylureas have a unique mode of action they interfere with a key enzyme required for plant cell growth - acetohydroxyacid synthase (AHAS, EC 2.2.1.6) [1, 2, 3] (see also Mark E. Thompson in this volume, Chapter 2.1 Biochemistry of the Target and Resistance ). AHAS is the enzyme responsible for the synthesis of the branched-chain amino acids valine, leucine and isoleucine. Inhibition of this enzyme disrupts the plant s ability to manufacture proteins, and this disruption subsequently leads to the cessation of all cell division and eventual death of the plant. 

Inhibitor studies indicate that serine, histidine and, perhaps tyrosine, residues are involved in the active site of the enzyme (Hirayama et al., 1975). Activity toward membrane-bound phospholipids (or phospholipid liposomes) is considerably enhanced by detergents. Of a range of surface-active agents studied, unsaturated free fatty acids were the most effective (Gal-liard, 1971b). For example, although a crude extract of potato hydrolyzes mitochondrial or liposome-bound lipids, the purified enzyme is inactive unless a detergent is added the factor responsible for enhancement in crude extracts was identified as a mixture of free fatty acids. Thus, the reaction on membrane lipids is autocatalytic free fatty acids released by the enzyme disrupt membrane structures to allow access of the enzyme to the substrate. The activity of acyl hydrolase from potato on mitochondrial lipids has been confirmed by Hasson and Laties (1976b). 

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