Inhibition, of system

Javitt DC, Duncan L, Balia A, Sershen H. 2005a. Inhibition of system A-mediated glycine transport in cortical synaptosomes by therapeutic concentrations of clozapine Implications for mechanisms of action. Mol Psychiatry... 

Aeromonas phenologenes), and lactate (Hansenula anomala). The inhibition of systems has proven successful in pyruvate monitoring Streptococcus faecium) by inhibiting glycolysis with iodoacetamide and tyrosine decarboxylase with tyramine, and in microbial detection of glutamic acid Bacillus subti-lis) treated with chloromercuribenzoate and sodium fluoride to inhibit glucose uptake and metabolism. 

In freshly isolated rat hepatocytes, Na -dependent cysteine transport is not inhibited by MeAIB and is restricted to System ASC (10, 23). However, the reciprocal is not true, that is, cysteine does inhibit System A activity (10). Like glutamine and histidine, cysteine represents a specific test substrate for a Na" -dependent system other than System A, yet it cannot be used as a system-specific inhibitor because of its noncompetitive inhibition of System A. 

The characteristics for the noncompetitive inhibition of System A have not been described in detail. This type of inhibition suggests that the protein may contain an additional amino acid binding site, other than the substrate site. Enzyme studies indicate that the inhibitor can bind to either the free carrier or the carrier-substrate complex to form a carrier-substrate-inhibitor complex which is inactive (37). 

The physiological significance of the noncompetitive inhibition of System A activity is still subject to speculation. One can estimate the effect of glutamine s inhibitory action [K, = 12 mM, see (9)] on the uptake of alanine using values of 0.26 mM, 4 mM, and 2.2 nmol mg" protein 30... 

Dolais-Kitabgi et al. (51) have taken an alternative approach to the study of glucocorticoids by isolating hepatocytes from rats after adrenalectomy. Using these cells in suspension, they showed that adrenalectomy caused a decrease in the activity of System A. A time course of Na -de-pendent AIB transport suggested that the net accumulation of the amino acid was reduced to a greater degree than the initial rate of uptake, but the authors did not comment as to whether the efflux of AIB was increased in the experimental cells. Treatment of the adrenalectomized animals with cortisone prior to isolation of the hepatocytes completely reversed the inhibition of System A (51). 

As mentioned in Section IX-2A, binary systems are more complicated since the composition of the nuclei differ from that of the bulk. In the case of sulfuric acid and water vapor mixtures only some 10 ° molecules of sulfuric acid are needed for water oplet nucleation that may occur at less than 100% relative humidity [38]. A rather different effect is that of passivation of water nuclei by long-chain alcohols [66] (which would inhibit condensation note Section IV-6). A recent theoretical treatment by Bar-Ziv and Safran [67] of the effect of surface active monolayers, such as alcohols, on surface nucleation of ice shows the link between the inhibition of subcooling (enhanced nucleation) and the strength of the interaction between the monolayer and water. 

Acrylonitrile is beheved to behave similarly to hydrogen cyanide (enzyme inhibition of cellular metaboHsm) (150) and is befleved to be a potential carcinogen (151). It can also affect the cardiovascular system and kidney and Hver functions (150). Eurther information on the toxicology and human exposure to acrylonitrile is available (152—154) (see Acrylonitrile). 

J. W. Hastie and D. W. BonneU, Molecular Chemist of Inhibited Combustion Systems, Feport NBSIF 80-2169, Nad. Buieau of Standards, Washington, D.C., 1980. 

Mode of Motion. The cyclodienes, like lindane and toxaphene, affect the nerve axon produciag hyperactivity, convulsions, prostration, and death. The biochemical lesion is the competitive inhibition of the y-aminobutyric acid (GABA) neurotransmitter binding site of the nerve axon. Spray workers with lengthy exposure to dieldrin have suffered from prolonged and repeated central nervous system disturbances produciag epileptiform coavulsioas. Similar disturbances occurred ia workers heavily exposed to chlordecoae. 

Molybdate is also known as an inhibitor of the important enzyme ATP sulfurylase where ATP is adenosine triphosphate, which activates sulfate for participation in biosynthetic pathways (56). The tetrahedral molybdate dianion, MoO , substitutes for the tetrahedral sulfate dianion, SO , and leads to futile cycling of the enzyme and total inhibition of sulfate activation. Molybdate is also a co-effector in the receptor for steroids (qv) in mammalian systems, a biochemical finding that may also have physiological implications (57). 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

Enzyme Inhibition. Some materials produce toxic effects by inhibition of biologically vital enzyme systems, leading to an impairment of normal biochemical pathways. The toxic organophosphates, for example, inhibit the cholinesterase group of enzymes. An important factor in thek acute toxicity is the inhibition of acetylocholinesterase at neuromuscular junctions, resulting in an accumulation of the neurotransmitter material acetylcholine and causing muscle paralysis (29) (see Neuroregulators). 

Several synthetic amino acids (63—65) have been identified that excite inhibition of the fibrinolytic system (Table 8). 

The higher frequencies of the /3-lactam carbonyl absorption in fused systems has been attributed to increased inhibition of amide resonance as the /3-lactam ring becomes less planar (b-72mI50900 p. 303). For the 3-cephems (61) there is also the possibility of enamine resonance which could further reduce the ability of the /3-lactam nitrogen to contribute to amide resonance. 

DEVELOPMENT OF A CHEMILUMINESCENCE DETECTION OF HERBICIDES RELATIVE TO THE MEDIATED INHIBITION OF THYLAKOIDS IN A ji-FLUIDIC SYSTEM... 

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