Tyrosine, hydroxylation

Steiner, U., Schhemann, W., and Strack, D., Assay for tyrosine hydroxylation activity of tyrosinase from betalain-forming plants and cell cultures, Anal. Biochem., 238, 72, 1996. 

Smyth, D.G. (1967) Acetylation of amino and tyrosine hydroxyl groups./. Biol. Chem. 242, 1592-1598. Smyth, D.G., Blumenfeld, O.O., and Konigsberg, W. (1964) Reaction of N-ethylmaleimide with peptides and amino acids. Biochem. J. 91, 589. 

A 5-(methylthio)methyl-substituted derivative (cis-28) of ( + )-3-PPP has been reported [91]. The background to the study was the structural similarity between pergolide (29) and (cis-28). However, the biological testing of (cis-28) showed that it is inactive in vivo (GBL model), while an in vitro assay (inhibition of tyrosine hydroxylation) showed (cis-28) to be equipotent to racemic 3-PPP itself. These results indicate that the steric bulk in (cis-28) is not compatible with potent DA receptor interaction. However, since compound (cis-28) was not resolved, there is a possibility that one or both of the enantiomers of (cis-28) might have antagonistic properties [89]. 

Typically, the hydrogen bond donor for the tetrahedral intermediate oxyanion is the amide NH group. In contrast, in enolate oxyanion holes, a much more variable range of hydrogen bond donors is observed, such as water, a tyrosine hydroxyl. 

Kiuchi K, Hirata Y, Minami M, et al Effect of 7- 3-[4-(2,3-dimethylphe-nyl)piperazinyl]propoxy -2(lH)-quinolinone (OPC-4392), a newly synthesized agonist for presynaptic dopamine D2 receptor, on tyrosine hydroxylation in rat striatal slices. Life Sci 42 343-349, 1988 Lehman AF, Lieberman JA, Dixon LB, et al Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 161 (suppl 2) 1-56, 2004... 

On the basis of the simulations, we proposed (70) a slightly modified mechanism for tyrosine hydroxylation (Fig. 30). 

Phenylalanine and tyrosine Hydroxylation of phenylalanine leads to the formation of tyrosine (Figure 20.7). This reaction, catalyzed by phenylalanine hydroxylase, is the first reaction in the catabolism of phenylalanine. Thus, the metabolism of phenyl alanine and tyrosine merge, leading ultimately to the formation of fumarate and acetoacetate. Phenylalanine and tyrosine are, therefore, both glucogenic and ketogenic. 

Imidazole, lysine amino groups, and tyrosine hydroxyl groups react with diethylpyrocarbonate... 

The binding of a hormone or growth factor (a ligand) to a dimeric receptor activates the protein kinase domain of the receptor which phosphorylates a number of tyrosine hydroxyl groups of the receptor itself. This autophosphorylation is followed by a variety of events, which include phosphorylation of tyrosine side chains of various other proteins.426 An-... 

Activation of neostriatal tyrosine hydroxylase was observed when cyclic AMP was added to high speed supernatants from rat neostriatum (133). Intraventricular injection of dibutyryl cyclic AMP stimulated tyrosine hydroxylation in the neostriatum (134). However, it is still questionable if under physiological conditions this cyclic AMP involvement in the feedback control of tyrosine hydroxylase activity is mediated by presynaptic dopamine receptors or by presynaptic allo-receptors. In addition, if a dopamine sensitive adenylate cyclase is involved in the regulation of neostriatal tyrosine hydroxylase activity it is relevant to know if this adenylate cyclase is linked to a D-1 and/or a D-2 receptor. At this point in time experimental data are not in favour of the presence of a D-l receptor linked to an adeiylate cyclase on the varicosities of dopaminergic neurons in the neostriatum. E.g. concentrations of dopamine agonists stimulating cyclic AMP formation inhibit tyrosine... 

A group of receptors exists that responds to so-called growth factors such as insulin, epidermal growth factor, platelet-derived growth factor, etc. These receptors have an extracellular domain that binds the growth factor and an intracellular domain that possesses latent kinase activity. The interaction of insulin, for example, results in autophosphorylation of the intracellular domain and subsequent internalization of the insulin-receptor complex. The internalized complex now possesses the properties of a tyrosine kinase and can phosphorylate cell substrates that produce the appropriate intracellular effect. However, these kinases differ from the usual protein kinases in that they phosphorylate proteins exclusively on tyrosine hydroxyl residues. The ensemble of proteins phosphorylated by the insulin receptor has not yet been identified, but there is supportive evidence that tyrosine kinase activity is required for the major actions of insulin. For example, it is possible that a membrane-linked glucose transport system becomes activated following insulin-stimulated phosphorylation. 

Nisenbaum LK, Abercrombie ED (1992) Enhanced tyrosine hydroxylation in hippocampus of chronically stressed rats upon exposure to a novel stressor. J Neuro-chem 58 276-281. 

In a third pathway, electrons flow from the N1 position of flavin via a hydrogen bond to Gly 305(N), on through backbone to the Tyr 306 side-chain, followed by a jump from the tyrosine hydroxyl to the methyl CMC atom of heme. The path with weakest coupling involves a through-space jump from the flavin 02 to Trp 391, then a jump to Cys 714 SG, which is covalently linked to the heme. 

A new motif for OP binding to tyrosine has been identified. Almost all proteins appear to be capable of binding OP covalently on tyrosine. Whether or not OP will bind to tyrosine in vivo will depend on the concentration of the protein, the concentration of the OP, and the ionization status of the tyrosine hydroxyl group. The latter factor appears to be dependent on the presence of nearby positively charged residues. 

NE is synthesized by tyrosine hydroxylation (meta ring position) followed by decarboxylation and side chain p carbon hydroxylation. The synthesis of this catecholamine is regulated by tyrosine hydroxylase. Tyrosine hydroxylation is also a key step in the synthesis of two other important catecholamines, dopamine and epinephrine. NE is packaged via active transport into synaptic (or chromaffin) vesicles prior to release by neuronal depolarization. The effects of NE are mediated by adrenergic receptors (a or P) which are G protein coupled resulting in either increases or decreases in smooth muscle tone as well as increases in cardiac rate and contractility. These effects arise out of receptor mediated increases in intracellular Ca and activation or inhibition of various protein kinases. The effects of NE are terminated essentially as a result of its active transport into the presynaptic nerve ending via an energy and Na" dependent process which utilizes the norepinephrine transporter (NET). Ultimately, NE and other catecholamines are metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). 

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