Glutamate mechanisms

Aghajanian GK, Marek GJ. Serotonin model of schizophrenia emerging role of glutamate mechanisms. Brain Res Brain Res Rev 2000 31 302-312. 

Fig. 15 Natural FPGS-catalyzed ligation for formation of folylpoly-y-glutamate, mechanism-based FPGS inhibitors, prior phosphonic and phosphinic acids inhibitors...

In transamination an amine group is transferred from L glutamic acid to pyruvic acid An outline of the mechanism of transamination is presented m Figure 27 4... 

Crystallization Method. Such methods as mechanical separation, preferential crystallisation, and substitution crystallisation procedures are included in this category. The preferential crystallisation method is the most popular. The general procedure is to inoculate a saturated solution of the racemic mixture with a seed of the desired enantiomer. Resolutions by this method have been reported for histidine (43), glutamic acid (44), DOPA (45), threonine (46), A/-acetyl phenylalanine (47), and others. In the case of glutamic acid, the method had been used for industrial manufacture (48). 

Work in the mid-1970s demonstrated that the vitamin K-dependent step in prothrombin synthesis was the conversion of glutamyl residues to y-carboxyglutamyl residues. Subsequent studies more cleady defined the role of vitamin K in this conversion and have led to the current theory that the vitamin K-dependent carboxylation reaction is essentially a two-step process which first involves generation of a carbanion at the y-position of the glutamyl (Gla) residue. This event is coupled with the epoxidation of the reduced form of vitamin K and in a subsequent step, the carbanion is carboxylated (77—80). Studies have provided thermochemical confirmation for the mechanism of vitamin K and have shown the oxidation of vitamin KH2 (15) can produce a base of sufficient strength to deprotonate the y-position of the glutamate (81—83). 

Figure 2 A glutamate side chain partitioned into quantum and classical regions. The terminal CH2C02 group IS treated quantum mechanically, and the backbone atoms are treated with the molecular mechanics force field.

FIGURE 14.22 Glutamate aspartate aminotransferase, an enzyme conforming to a double-displacement bisnbstrate mechanism. Glutamate aspartate aminotransferase is a pyridoxal phosphate-dependent enzyme. The pyridoxal serves as the —NH, acceptor from glntamate to form pyridoxamine. Pyridoxamine is then the amino donor to oxaloacetate to form asparate and regenerate the pyridoxal coenzyme form. (The pyridoxamine enzyme is the E form.)... 

It has a molecular weight of about 34000 and contains one Zn tetrahedrally coordinated to two histidine N atoms, a carboxyl O of a glutamate residue, and a water molecule. The precise mechanism of its action is not finally settled in spite of the intensive study of model systems, but it is agreed that the first step is coordination of... 

One of the biological pathways by which an amine is converted to a ketone involves two steps (1) oxidation of the amine by N.AD+ to give an imine, and (2) hydrolysis of the imine to give a ketone plus ammonia. Glutamate, for instance, is converted by this process into a-ketoglutarate. Show the structure of the imine intermediate, and propose mechanisms for both steps. 

Most amino acids lose their nitrogen atom by a transamination reaction in which the -NH2 group of the amino acid changes places with the keto group of ct-ketoglutarate. The products are a new a-keto acid plus glutamate. The overall process occurs in two parts, is catalyzed by aminotransferase enzymes, and involves participation of the coenzyme pyridoxal phosphate (PLP), a derivative of pyridoxine (vitamin UJ. Different aminotransferases differ in their specificity for amino acids, but the mechanism remains the same. 

The amino acid serine is biosynthesized by a route that involves reaction of 3-phosphohydroxypyruvate with glutamate. Propose a mechanism. 

Seeburg PH, Higuchi M, Sprengel R (1998) RNA editing of glutamate receptor channels mechanism and physiology. Brain Res Brain Res Rev 26 217-219... 

For many years it was believed that the brain mechanisms underlying the effects of psychedelic hallucinogens and dissociative anesthetics were separate and distinct. Indeed, there has been considerable debate about which represents the best drag model of schizophrenia. However, recent data show that the two classes of psychotomimetic drags share a common final pathway involving an increase in the release of the excitatory neurotransmitter glutamate. 

Transduction mechanism Inhibition of adenylyl cyclase stimulation of tyrosine phosphatase activity stimulation of MAP kinase activity activation of ERK inhibition of Ca2+ channel activation stimulation of Na+/H+ exchanger stimulation of AM PA/kainate glutamate channels Inhibition of forskol in-stimulated adenylyl cyclase activation of phos-phoinositide metabolism stimulation of tyrosine phosphatase activity inhibition of Ca2+ channel activation activation of K+ channel inhibition of AM PA/ kainate glutamate channels inhibition of MAP kinase activity inhibition of ERK stimulation of SHP-1 and SHP-2 Inhibition of adenylyl cyclase stimulation of phosphoinositide metabolism stimulation of tyrosine phosphatase activation of K+ channel inhibi-tion/stimulation of MAP kinase activity induction of p53 and Bax Inhibition of adenylyl cyclase stimulation of MAP kinase stimulation of p38 activation of tyrosine phosphatase stimulation of K+ channels and phospholipase A2 Inhibition of adenylyl cyclase activation/ inhibition of phosphoinositide metabolism inhibition of Ca2+ influx activation of K+ channels inhibition of MAP kinase stimulation of tyrosine phosphatase... 

The exocytotic release of neurotransmitters from synaptic vesicles underlies most information processing by the brain. Since classical neurotransmitters including monoamines, acetylcholine, GABA, and glutamate are synthesized in the cytoplasm, a mechanism is required for their accumulation in synaptic vesicles. Vesicular transporters are multitransmembrane domain proteins that mediate this process by coupling the movement of neurotransmitters to the proton electrochemical gradient across the vesicle membrane. 

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