Tyrosine, 494 Table

Several compounds can be oxidized by peroxidases by a free radical mechanism. Among various substrates of peroxidases, L-tyrosine attracts a great interest as an important phenolic compound containing at 100 200 pmol 1 1 in plasma and cells, which can be involved in lipid and protein oxidation. In 1980, Ralston and Dunford [187] have shown that HRP Compound II oxidizes L-tyrosine and 3,5-diiodo-L-tyrosine with pH-dependent reaction rates. Ohtaki et al. [188] measured the rate constants for the reactions of hog thyroid peroxidase Compounds I and II with L-tyrosine (Table 22.1) and showed that Compound I was reduced directly to ferric enzyme. Thus, in this case the reaction of Compound I with L-tyrosine proceeds by two-electron mechanism. In subsequent work these authors have shown [189] that at physiological pH TPO catalyzed the two-electron oxidation not only L-tyrosine but also D-tyrosine, A -acetyltyrosinamide, and monoiodotyrosine, whereas diiodotyrosine was oxidized by a one-electron mechanism. 

During years of mass spectrometry analysis, we had consistently identified OP-labeled tubulin in mouse brain. Therefore, we studied pure bovine tubulin (Cytoskeleton, Inc.) by treating it with soman, sarin, FP-biotin, DFP, chlorpyrifos oxon, and dichlorvos. We isolated the OP-labeled tryptic peptides and analyzed them by fragmentation in the QTRAP 2000 and QTRAP 4000 mass spectrometers. We identified five OP-labeled peptides in tubulin (Grigoryan et al, 2008). In every peptide, the OP was covalently attached to tyrosine (Table 56.1). 

Similar mass spectrometry experiments with pure human and mouse transferrin (Li et al., 2008c), and with human kinesin showed that the OP label was consistently on tyrosine (Table 56.1). Studies with human plasma identified OP labeling on tyrosine in apolipoprotein and alpha-2-glyco-protein. Aggressive treatment of hiunan albumin with FP-biotin and chlorpyrifos oxon led to identification of seven OP-labeled tyrosines (Ding et al, 2008). Finally, we found that synthetic peptides made a covalent bond with DFP, chlorpyrifos oxon, and dichlorvos (Table 56.1). Mass spectrometry conclusively proved that the OP was attached to tyrosine. 

Experiments with a series of 2V-acylated tyrosine peptides indicated that cleavage yield was relatively independent of the nature of the A -acyl group preceding or of the amino acid following tyrosine (Table XI). 

The results of nonselective iodination of the tyrosines of cytochrome c almost exactly parallel the nitration of tyrosine-67 described earlier. Tyrosine-67 is preferentially iodinated, indicating that the polypeptide framework of cytochrome c is suflSciently elastic to give KIs access to the interior. As with nitration, the pXa of the state III to state IV ligand transition of normal cytochrome c is lowered from pH 9.35 to 5.9, probably as a consequence of the lower pX values of iodinated and nitrated tyrosine (Table XVI). In both cases, the new ligand above the transition point probably is the ionized tyrosine itself rather than lysine as in the normal state IV. Results of experiments with acetylation of tyrosines (228,229) have been similar but not as conclusive. 

Other studies performed on the second-derivative spectrum (Ragone et al. 1984) have shown that the ratio r between two peak to trough distances (287-283 and 295-290) was related to the tyrosine / tryptophan ratio and was found dependent on the surrounding medium polarity of tyrosine. Table 1.5 shows the values of r for different proteins measured in the native (r ) and denatured (r ) states. We can notice that r increases when the proteins are denatured, i.e., tyrosines are much more exposed to the solvent in the denatured state. The increase of r with the protein deiiaturation is in principle dependent on the tyrosines locations in the proteins in the native state. 

The pK values of the amino acids depend upon the structure of the amino acid. The pA values of the a-carboxyl groups range from 1.81 for histidine to 2.58 for phenylalanine. The pA values of the a-amino groups range from 8.8 for histidine to 10.78 for tyrosine (Table 27.1). 

For convenience of discussion, the metabolites have been classified according to their biosynthetic derivation, either established by experiment or implied by structure, from phenylalanine (Table I), tryptophan (Table II), and tyrosine (Table III). Table IV lists metabolites of unknown structure. 

Table 9. Alkaloids Derived from Tyrosine as a Ce-C, Fragment and Phenylalanine as a Ce-C3 Fragment...

Many kinds of amino acids (eg, L-lysine, L-omithine, t-phenylalanine, L-threonine, L-tyrosine, L-valine) are accumulated by auxotrophic mutant strains (which are altered to require some growth factors such as vitamins and amino acids) (Table 6, Primary mutation) (22). In these mutants, the formation of regulatory effector(s) on the amino acid biosynthesis is genetically blocked and the concentration of the effector(s) is kept low enough to release the regulation and iaduce the overproduction of the corresponding amino acid and its accumulation outside the cells (22). 

Biosynthesis. Biochemical studies on dalbaheptides have been reviewed (92,97). Experiments with and H have shown that in vancomycin (39), D-tyrosine is the precursor of D-/> -hydroxyphenyiglycine and P-hydroxy-y -chlorotyrosine, and acetate the precursor of the two y jy -dihydroxyphenyiglycines (98). Similar results using either or radioactively labeled material have been reported for avoparcin (Table 5) (23), ristocetin (Table 2) (99,100), ardacin (Table 3) (101), and A47934 (102). 

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)... 

However, the use of a HPLC separation step enabled a remarkable acceleration of the deconvolution process. Instead of preparing all of the sublibraries, the c(Arg-Lys-O-Pro-O-P-Ala) library was fractionated on a semipreparative HPLC column and three fractions as shown in Fig. 3-2 were collected and subjected to amino acid analysis. According to the analysis, the least hydrophobic fraction, which eluted first, did not contain peptides that included valine, methionine, isoleucine, leucine, tyrosine, and phenylalanine residues and also did not exhibit any separation ability for the tested racemic amino acid derivatives (Table 3-1). 

Major costs for raw materials are those for glucose, tyrosine, tryptophan and salts. The figures are given in Table 85. 

Growth Factors. Table 1 Summary of a num ber of growth factor families, the tyrosine kinase receptors they bind, and the major physiological consequences of their interactions... 

Main differences between monoclonal antibodies and small-molecule receptor tyrosine kinases are described in Table 2. 

Tyrosine Kinase Inhibitors. Table 1 Tyrosine kinase inhibitors approved for clinical use (by July 2007)... 

PTKs can be subdivided into two large families, receptor tyrosine kinases (RTKs) and non-RTKs. The human genome encodes for a total of 90 tyrosine kinases of which 32 are nonreceptor PTKs that can be placed in 10 subfamilies (Fig. 1). All nonreceptor PTKs share a common kinase domain and usually contain several additional domains that mediate interactions with protein-binding partners, membrane lipids, or DNA (Table 1). These interactions may affect cellular localization and the activation status of the kinase or attract substrate proteins for phosphorylation reactions. 

The mechanical properties of tyrosine-derived poly(iminocarbon-ates) were investigated using the procedures described in ASTM standard D882-83 (Table 2). Solvent-cast, thin polymer films were prepared, cut into the required shape, and tested in an Instron stress strain tester. Since the films were unoriented, noncrystalUne samples, the results are representative of the bulk properties of the polymers. In order to put these results into perspective, several commercial polymers were tested under identical conditions. In addition, some literature values were included in Table 2. 

Humans can synthesize 12 of the 20 common amino acids from the amphiboHc intermediates of glycolysis and of the citric acid cycle (Table 28-1). While nutritionally nonessenrial, these 12 amino acids are not nonessential. AH 20 amino acids are biologically essential. Of the 12 nutritionally nonessential amino acids, nine are formed from amphibolic intermediates and three (cysteine, tyrosine and hydroxylysine) from nutritionally essential amino acids. Identification of the twelve amino acids that humans can synthesize rested primarily on data derived from feeding diets in which purified amino acids replaced protein. This chapter considers only the biosynthesis of the twelve amino acids that are synthesized in human tissues, not the other eight that are synthesized by plants. 

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