Activities of tyrosine

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... 

Scheme 18 Possible carboxylate group participation in the activation of tyrosine in tyrosyl-tRNA synthetase...

Certainly the activity of tyrosine hydroxylase is greater in the DA neurons of the substantia nigra (17.5 nmol dopa synthesised/mg protein/h) than in the NA neurons of the locus coeruleus (4-5), as is the turnover of the amine itself (1.7 pg/h) compared with that of NA (1.0) (see Bacopoulus and Bhatnager 1977). In the caudate nucleus and nucleus accumbens the turnover of DA is even higher at 7.4 and 2-6 pg/g/h respectively. 

Lequea et al. used the activity of tyrosine apodecarboxylase to determine the concentration of the enzyme cofactor pyridoxal 5 -phosphate (vitamin B6). The inactive apoenzyme is converted to the active enzyme by pyridoxal 5 -phosphate. By keeping the cofactor the limiting reagent in the reaction by adding excess apoenzyme and substrate, the enzyme activity is a direct measure of cofactor concentration. The enzymatic reaction was followed by detecting tyramine formation by LCEC. The authors used this method to determine vitamin B6 concentrations in plasma samples. 

D. indicus Gaertn. is known to abound with anthraquinones, but its pharmacological potential remains unexplored to date (20,21). Note that damnacanthal is a common component of the Damnacanthus species. Faltynek et al. made the interesting observation that damnacanthal inhibits the enzymatic activity of tyrosine kinase, which is involved in the propagation of metastases (22). An interesting development from this observation would be to assess the topoisomerase inhibitory activity of the Damnacan-thus species, an activity that could be associated with tyrosine kinase inhibition, hence enormous chemotherapeutic potentials. 

Griffiths, J., Marley, P.D. Ca2+-dependent activation of tyrosine hydroxylase involves MEK1. Neuroreport. 12 2679, 2001. 

Waymire, J. C. and Craviso, G. L. Multiple site phosphorylation and activation of tyrosine hydroxylase. Adv. Protein Phosphatases 7 501-513,1993. 

There are also several reports of Li+-induced effects upon the endorphins (see ref. 162). More recently it has been shown that Li+ also enhances the activity of tyrosine aminopeptidase in rat pituitary gland [167]. This could result in changes in the levels of the enkephalins which are primarily degraded by aminopeptidases via cleavage of the tyrosine-glycine amide bond [168]. 

One of the first pieces of evidence for the mechanism of this reaction involved an attempt to develop a new assay for the activity of tyrosine synthase, which converts phenylalanine to tyrosine. A tritium was placed in the para position of phenylalanine, and it was assumed that oxidation of this position would lead to the loss of tritium and the rate of this loss would be a measure of the activity of the enzyme (Fig. 4.76). 

The most sensitive indicator of neurological effects in animals appears to be alterations in the levels of neurotransmitters in the brain. In rats exposed to bromomethane for 8 hours, there was a significant decrease in the hypothalamic concentration of norepinephrine and a decrease in the activity of tyrosine hydroxylase at an exposure level of 31 ppm, but not at 16 ppm (Honma 1987). 

Tanaka, S., L. Neff, R. Baron, and J. B. Levy. Tyrosine phosphorylation and translocation of the c-Cbl protein after activation of tyrosine kinase signaling pathways. J Biol Chem. 270 14347-14351.1995. 

Starting from the activated receptor, a large number of reactions can be set in motion (Fig. 5.5). One main route of signal transmission takes place by activation of G-prote-ins, another via activation of tyrosine-specific protein kinases, and a further route is via activation of ion chaimels. In the further course of G-protein mediated signal transmis-... 

The extent of tyrosine phosphorylation of signal proteins is determined both by the activity of the tyrosine kinases and also the activity of tyrosine-specific protein phosphatases. If the total activity of both enzymes in the cell is considered, it is found that there is a preponderance of protein tyrosine phosphatase activity compared to tyrosine kinase activity. In contrast, the activities of the Ser/Thr-specific protein kinases and protein phosphatases are approximately balanced. It is estimated that the activity of the protein tyrosine phosphatases is about 3-4 orders of magnitude higher than the activity of the protein tyrosine kinases. With this relationship between the activities, it is not surprising that the net level of tyrosine phosphorylation in the cell is very low and that tyrosine phosphorylation is often only transient. Consequently, it took a relatively long time until the importance of tyrosine phosphorylation for signal transduction was assessed correctly. 

At about the same time, Gunsalus and coworkers noticed that the activity of tyrosine decarboxylase produced by lactic acid bacteria was unusually low when the medium was deficient in pyridoxine. Addition of pyridoxal plus ATP increased the decarboxylase activity of cell extracts.146 PLP was synthesized and was found to be the essential coenzyme for this and a variety of other enzymes.147... 

F Results from difference energy diagrams for the activation of tyrosine... 

Blockade of angiogenesis is useful in tumor therapy (Ferrara and Kerbel 2005 Menakuru et al. 2008). Over the last decade, the most extensively examined proan-giogenic molecule has been VEGF, a secreted protein that, through activation of tyrosine kinase receptors, promotes key events in angiogenesis that include increases in vascular permeability, and stimulation of endothelial cell proliferation and migration (Ferrara 2003). 

Blockade of dopamine receptors by administration of neuroleptics has been demonstrated to induce an allosteric activation of tyrosine hydroxylase which is accompanied by an increase in the turnover rate of dopamine and accumulation of dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA) (103-106). ... 

Aguila-Mansilla N, Kedzierski W, Porter JC (1993) Localization of a defect in hypothalamic dopaminergic neurons of aged brain that results in impaired PKA-dependent activation of tyrosine hydroxylase. J Pharmacol Exp Ther 257 171-175. 

Berry SA, Gudelsky GA (1992) Evidence for protein kinase-C meditation of the neurotensin-induced activation of tyrosine hydroxylase in tuberoinfundibular dopaminergic neurons. Endocrinology 757 1207-1211. 

According to the authors tetrahydrobiopterin has a range of co-factor roles, including being required for the activity of tyrosine and tryptophan hydroxylase, enzymes that are essential for dopamine and serotonin synthesis. They speculated that something present in the heroin pyrolysate, a product formed when heroin is heated to 250° C, inhaled by the patient, acted as a reversible inhibitor of tetrahydrobiopterin metabolism, providing a biochemical explanation for impairment of dopamine metabolism and Parkinsonism in this case. 

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