Glycine inhibition

Aprison M H and Nadi N S. (1978) Glycine. Inhibition from the Sacrum to the Medulla, in Ammo Acids as Chemical Transmitters (Fonnum, F., ed ), pp. 531-571, Plenum, New York. 

E. Racker Have you tried to find out whether glutamylcysteine or glycine inhibits the exchange reaction ... 

Results forthcoming from the literature do not always assist in building a picture of events. The observation [65] that 2- and 4-hydroxylation of biphenyl was competitively inhibited by polysorbate 80 in the hamster contrasts with the finding that in the rat, polysorbate 80 (2mM) had no effect on the linear microsomal demethylation of aminopyrine (also a Type V substrate) [66]. The question arises whether surfactants such as polysorbate 80 produce their effects by interaction as an alternative substrate or by perturbation of a membrane bound enzyme system. Commercial samples of polysorbate 80, Brij 35 and Triton X-100 all enhance the activity of a sarcosine dehydrogenase isolated from a strain of Pseudomonas, due to the presence of free oleic acid in these non-ionic surfactants. Deoxycholate and a sarcosine surfactant (N-dodecanoyl N-methyl glycine) inhibit activity [67]. Correlations between the CMC of the non-ionic surfactants and the concentrations required for enzyme activation are seen in Table 10.9. 

Figure 2 Stability of /3-poly(L-malate) measured by its activity to inhibit purified DNA polymerase a of P. polyceph-alum. The relative degree of inhibition is shown (100 rel. units refer to complete inhibition). The DNA polymerase assay was carried out in the presence of 5 /tg/ml /S-poly(L-malate) as described [4]. The polymer was preincubated for 7 days at 4°C in the following buffer solutions (50 mM) KCl/HCl (—A—). Citrate (—V—). 2-(A/-Morpholino)-ethanesulfonic acid, sodium salt (—O—). Sodium phosphate (— —). N-(2-Hydroxyethyl)piperazine-N -(2-ethanesul-fonic acid), sodium salt (— — ). N,N-b s (2-Hydroxyethyl)-glycine, sodium salt (—T—). Tris/HCl (— —). 3-(Cyclo-hexylamino)-l-propanesulfonic acid, sodium salt (— —).

The other important molecular target of ethanol is the N-methyl-D-apartate receptor (NMDA-R), which is acutely inhibited although the mechanism is not clear. It was speculated that at least in some brain region the coactivating glycine sites are involved and/or the coactivating polyamine sites. The receptors containing... 

Tetanus is a disease caused by the release of neurotoxins from the anaerobic, spore-forming rod Clostridium tetani. The clostridial protein, tetanus toxin, possesses a protease activity which selectively degrades the pre-synaptic vesicle protein synaptobrevin, resulting in a block of glycine and y-aminobutyric acid (GABA) release from presynaptic terminals. Consistent with the loss of neurogenic motor inhibition, symptoms of tetanus include muscular rigidity and hyperreflexia. The clinical course is characterized by increased muscle tone and spasms, which first affect the masseter muscle and the muscles of the throat, neck and shoulders. Death occurs by respiratory failure or heart failure. 

Since biosynthesis of IMP consumes glycine, glutamine, tetrahydrofolate derivatives, aspartate, and ATP, it is advantageous to regulate purine biosynthesis. The major determinant of the rate of de novo purine nucleotide biosynthesis is the concentration of PRPP, whose pool size depends on its rates of synthesis, utilization, and degradation. The rate of PRPP synthesis depends on the availabihty of ribose 5-phosphate and on the activity of PRPP synthase, an enzyme sensitive to feedback inhibition by AMP, ADP, GMP, and GDP. 

Figure 6, Magnesium in concentrations of 0.001-10 mM/l. produces no significant activation of alkaline phosphatase in EAE, DEA, or 2A2M1P buffers. It activates the enzyme in carbonate buffer but inhibits it in glycine buffer.

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