Of tyrosine

CgHiiNO. M.p. 282 C (decomp.). The naturally occurring substance is laevorotatory. It is an amino-acid isolated from various plant sources, but not found in the animal body. It is formed from tyrosine as the first stage in the oxidation of tyrosine to melanin. It is used in the treatment of Parkinson s disease. 

The last part of this account will be devoted to protein kinases and protein phosphatases and some recent results we have obtained for them. Protein kinases and phosphatases are signaling biomolecules that control the level of phosphorylation and dephosphorylation of tyrosine, serine or threonine residues in other proteins, and by this means regulate a variety of fundamental cellular processes including cell growth and proliferation, cell cycle and cytoskeletal integrity. 

Mercuric nitrite reaction (Millon s reaction). Dissolve a very small crystal of tyrosine in i ml. of water, add 1-2 drops of mercuric nitrate solution, and I drop of dil. HjSO, and then boil. Cool, add i drop of sodium nitrite solution and warm again a red coloration is obtained. 

Formalin coloration. To a small crystal of tyrosine, add 1 drop of 40% formalin, 1 ml. of water, and i ml. of cone. H2SO4. Boil gently a deep green coloration is developed. 

The phenolic hydroxyl group of tyrosine, the imidazole moiety of histidine, and the amide groups of asparagine and glutamine are often not protected in peptide synthesis, since it is usually unnecessary. The protection of the hydroxyl group in serine and threonine (O-acetylation or O-benzylation) is not needed in the azide condensation procedure but may become important when other activation methods are used. 

Above a pH of about 10 the major species present in a solution ] of tyrosine has a net charge of -2 Suggest a reasonable structure for this species J... 

FIGURE 27 5 Tyrosine is the biosynthetic precursor to a number of neurotransmit ters Each transformation IS enzyme catalyzed Hydroxy lation of the aromatic ring of tyrosine converts it to 3 4 dihyd roxyphenylalanine (l dopa) decarboxylation of which gives dopamine Hy droxylation of the benzylic carbon of dopamine con verts It to norepinephrine (noradrenaline) and methy lation of the ammo group of norepinephrine yields epi nephrine (adrenaline)... 

Thiocyanate ion, SCN , inhibits formation of thyroid hormones by inhibiting the iodination of tyrosine residues in thyroglobufin by thyroid peroxidase. This ion is also responsible for the goitrogenic effect of cassava (manioc, tapioca). Cyanide, CN , is liberated by hydrolysis from the cyanogenic glucoside finamarin it contains, which in turn is biodetoxified to SCN. 

One Anson unit is the amount of enzyme that, under standard conditions, digests hemoglobin at an initial rate, Hberating per minute an amount of TCA-soluble product which produces the same color with phenol reagent as one milliequivalent of tyrosine (91). 

DOPA in the bloodstream can be taken up into neural tissue and into tissue devoid of tyrosine hydroxylase, thus bypassing the rate-limiting enzymatic synthetic step (35). Uptake of DOPA by the brain is the basis of the therapeutic effect of DOPA in the treatment of Parkinson s disease (a... 

The 4-(dimethylaminocarbonyl)benzyl ether has been used to protect the phenolic hydroxyl of tyrosine. It is stable to CF3CO2H (120 h), but not to HBr/AcOH (complete cleavage in 16 h). It can also be cleaved by hydrogenolysis (H2/Pd-C). ... 

Figure 13.32 Regulation of the catalytic activity of members of the Src family of tyrosine kinases, (a) The inactive form based on structure determinations. Helix aC is in a position and orientation where the catalytically important Glu residue is facing away from the active site. The activation segment has a conformation that through steric contacts blocks the catalytically competent positioning of helix aC. (b) A hypothetical active conformation based on comparisons with the active forms of other similar protein kinases. The linker region is released from SH3, and the activation segment changes its structure to allow helix aC to move and bring the Glu residue into the active site in contact with an important Lys residue.

Several flaoraza reagents shown in Tables 3a and 3b (B, C, E, F, J, and K) are reactive enough to fluorinate an aromatic ring (Table 1). The ortho isomer predominates in the o/mlp mixture Reagent K has been used to prepare fluorinated derivatives of tyrosine and estradiol [77 (equation 35) (Table 1, entry 10)... 

Tyrosine.—On cooling, a brown, crystalline crust of impure tyrosine separates. It is filtered, dissolved in the least quantity of boiling water, boiled with a little animal charcoal, and filtered. Oit cooling, long, white, silky needles of tyrosine arc deposited. Yield. rborit 2 grams. 

A method that has been the standard of choice for many years is the Lowry procedure. This method uses Cn ions along with Folin-Ciocalteau reagent, a combination of phosphomolybdic and phosphotnngstic acid complexes that react with Cn. Cn is generated from Cn by readily oxidizable protein components, such as cysteine or the phenols and indoles of tyrosine and tryptophan. Although the precise chemistry of the Lowry method remains uncertain, the Cn reaction with the Folin reagent gives intensely colored products measurable spectrophotometrically. 

An isopropyl ether was developed as a phenol protective group that would be more stable to Lewis acids than would be an aryl benzyl ether. The isopropyl group has been tested for use in the protection of the phenolic oxygen of tyrosine during peptide synthesis."... 

The Msib group has been used for the protection of tyrosine. It is cleaved by reduction of the sulfoxide to the sulfide, which is then deprotected with acid. Reduction is achieved with DMF-SO3/HSCH2CH2SH or Bu4N I or with SiCWTFA. ... 

A case in point is hydrogenolysis of the 1-phenyl tetrazolyl ether of tyrosine, to phenylalanine 107). 

A mixture was made of L-tyrosine (18.1 g, 0.1 mol) benzoyl chloride (7.0 g, 0.05 mol) and 200 ml anhydrous THF. After stirring at reflux for 2 hours, the mixture was cooled to room temperature, and the precipitate of tyrosine hydrochloride filtered off (11 g, 46 meq. Cr). The THF was evaporated and the residue extracted with CCI4 (3 X 100 ml at reflux, discarded) and then dissolved in ethyl acetate (200 ml) filtering off insolubles. The ethyl acetate solution was evaporated to yield 13.2 g solid product, MP 159°-162°C (93%). The tyrosine was recovered (8 g) by neutralization with aqueous alkali, from the hydrochloride. 

Production of phenylalanine starts after depletion of tyrosine at about 6 hours. This is logical since the micro-oiganism needs a certain amount of tyrosine, for example to synthesise key enzymes, but synthesis of L-phenylalanine is feedback regulated if tyrosine is present. 

Presume that a yield of 20 g F1 of L-phenylalanine can be obtained. This is more realistic, based on patent literature, than the low yields in the example considered previously (section 8.6). This automatically means that more glucose will be needed. Let us again presume that instead of 35 g P glucose we now need 150 g l 1 to achieve this overall yield. The concentrations of the mineral salt are kept fire same to maintain good buffering capadty, whilst the concentration of tyrosine and tryptophan are also increased by a factor 4.3 (tyrosine 0.21 g F1 and tryptophan 0.11 g F1)... 

Fig. 4.1.13 A ribbon representation of the crystal structure of recombinant acquorin molecule showing the secondary structure elements in the protein. Alpha-helices are denoted in cyan, beta-sheet in yellow, loops in magenta coelenterazine (yellow) and the side chain of tyrosine 184 are shown as stick representations. From Head et al., 2000, with permission from Macmillan Publishers.

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