Oxidation of L-tyrosine

Heinecke et al. [191] studied the oxidation of L-tyrosine by the H202-MP0 system and showed that the main product of this reaction is dityrosine. They have also found that tyrosine successfully competed with chloride as a substrate for MPO that points out at the possibility of in vivo oxidation of tyrosine by MPO even in the presence of big physiological concentration (0.10-0.1 mol l-1) of chloride in human blood. It was also suggested that the tyrosyl radical formed at the catalytic oxidation of tyrosine by peroxidases may interact with... 

Oxidation of L-tyrosine, for selective introduction of a hydroxyl group at Cj of the tyrosine ring, can be accomplished in a purely synthetic manner by using a mixture of hydrogen peroxide and iron(II) sulfate mixture in water as an oxidant with permanent presence of oxygen [3]. 

A synthetic phaeomelanin can be easily obtained by the tyrosinase-catalyzed oxidation of L-tyrosine or L-dopa in the presence of excess L-cysteine at pH 6.8 followed by chromatography of the acid-soluble fraction on a Sephadex column. This procedure leads to the isolation of four major reddish brown pigments that are similar to natural... 

When the sorghum mlcrosomes were Isolated in the absence of 2-mer-captoethanol, the major product on oxidation of L-tyrosine was p-hydroxyphenylacetaldoxlme (aldoxime) (8). This reaction, which represents the 4-electron oxidative decarboxylation of L-tyrosine, again required NAOPB and 02- While no intermediates were detected in this conversion, this part of the reaction sequence has received further study described below. 

Systems which oxidize p-hydroxyphenylpyruvate have been found in hog liver (224,239), rabbit liver (766), rat liver (429,465,810) and dog liver (466,838). Soluble, mitochondria-free p-hydroxyphenylpyruvate oxidase from rat liver oxidizes 2,5-dihydroxyphenylpyruvic acid to acetoacetate at a rate comparable with that of the over-all oxidation of L-tyrosine (429), but will not oxidize 2,5-dihydroxyphenyl-alanine, gentisic acid, or the lactone of 2,5-dihydroxyphenylpyruvic acid (429). A purified rabbit liver oxidase transforms p-hydroxy-... 

Implanted relay modified-enzyme electrodes might find application also in selective and controlled electrochemical oxidation or reduction of biochemicals in a specific organ (e.g., the oxidation of L-tyrosine to L-Dopa). This would open a route to electrochemotherapy. 

Kinetic and activation parameters for the Ir(III)-catalysed oxidation of pentane-3-one and 4-methylpentane-2-one by cerium(IV) sulfate have been determined and a mechanism has been suggested. Ag(l)-catalysed oxidation of L-alanine with cerium(IV) in sulfuric acid is first order in Ce(lV) and L-alanine. A mechanism involving formation of free radicals has been suggested. Silver(I)-catalysed oxidation of L-tyrosine and A-acetyl L-tyrosine by Ce(lV) in sulfuric acid medium is proposed to proceed via an Ag(l)-reductant complex, which reacts with Ce(lV) to decompose in a rate-determining step. The active oxidizing species has been identified as Ce(S04)2. Kinetics of the oxidation of fiimaric acid with cerium(lV) in acid medium has been obtained and a mechanism has been suggested. ... 

The oxidation of L-tyrosine by hexachloroiridate(lV) exhibits first-order dependence on both Ir(IV) and L-tyrosine. The reaction rate increases with increase in ionic strength and decreases with increase in acidity. Dityrosine has been identified as the main product, activation parameters have been evaluated, and a mechanism has been suggested. DFT study of the oxidation of a guanine nucleotide by platinum(lV) indicated that a key step in the mechanism is electron transfer from guanine to platinum(lV). It has been shown that out of several different Pt(lV)-guanine adducts, one which is formed from replacement of an axial chlorine ligand in the platinum(lV) complex undergoes oxidation more easily. The oxidation of adenine is found to be more difficult as it involves disruption of an aromatic jt system. ... 

Ascorbic acid is involved in carnitine biosynthesis. Carnitine (y-amino-P-hydroxybutyric acid, trimethylbetaine) (30) is a component of heart muscle, skeletal tissue, Uver and other tissues. It is involved in the transport of fatty acids into mitochondria, where they are oxidized to provide energy for the ceU and animal. It is synthesized in animals from lysine and methionine by two hydroxylases, both containing ferrous iron and L-ascorbic acid. Ascorbic acid donates electrons to the enzymes involved in the metabohsm of L-tyrosine, cholesterol, and histamine (128). 

Marquez and Dunford [193] have studied the kinetics of L-tyrosine oxidation by MPO. They measured the rate constants for the reactions of MPO compounds I and II with tyrosine and dityrosine and found out that, comparing with HRP, LPO, and TPO, MPO is the most effective catalyst of tyrosine oxidation at physiological pH (Table 22.1). Furthermore, the rate constant for Reaction (9) with tyrosine turns out to be comparable with that for Reaction (16), confirming the possibility for tyrosine to compete in blood plasma with chloride, which is considered to be the major MPO substrate and a potent oxidizing agent against invading bacteria and viruses. 

Peroxidases have also been utilized for preparative-scale oxidations of aromatic hydrocarbons. Procedures have been optimized for hydroxylation of l-tyrosine, D-(-)-p-hydroxyphenylglycine, and L-phenylalanine by oxygen, di-hydroxyfumaric acid, and horseradish peroxidase (89). Lactoperoxidase from bovine milk and yeast cytochrome c peroxidase will also catalyze such hydroxylation reactions (89). 

Phenylglycines are important components of the vancomycin/teicoplanin antibiotics, and the conforma-tionally restricted amino acids contribute to the unique architecture and biological function of these clinically important NRPs. 4-Hydroxyphenylglycine is produced from L-tyrosine in a pathway that involves three enzymes. In the key step, a nonheme iron oxidase catalyzes the oxidative decarboxylation of the a-keto acid derivative of L-tyrosine resulting in loss of carbon dioxide and generation of the phenylglycine carbon framework. 

Anodic oxidation of halogenated tyrosines was studied in connection with some sponge metabolites (cavemicolin model compounds). The methyl exter of 3,5-dibromotyrosine afforded four different products in a 41 10 26 23 ratio with 23% overall yield as a result of equilibration. (Scheme 44) [93JCS(P2)3117], A related compound was obtained as a mixture of stereoisomers 56 from a Diels-Alder reaction between N-acetyldehydroalanine methyl ester and l-methoxy-l,3-cyclohexadiene (87TL2371). 

Oxidation of L-DOPA to L-dopaquinone is an important biological process, and dopaquinone is known to play a key role in the oxidative conversion of tyrosine into melanins, the primary pigments of skin and hair. It has been found that under biomimetic conditions both resorcinol and phloroglucinol inhibit this action of L-DOPA, and the compound 1 was isolated from the enzyme-catalysed L-DOPA/phloroglucinol reaction. Compound 1 could also be prepared by fenicyanide oxidation of a mixture of L-DOPA and phloroglucinol. 

M2. MacMillan-Crow, L. A., Crow, J. P., and Thompson, J. A., Peroxynitrite-mediated inactivation of manganese superoxide dismutase involves nitration and oxidation of critical tyrosine residues. Biochemistry 37, 1613-1622 (1998). 

Ty initiates melanin synthesis by the hydroxylation of L-tyrosine to 3,4-dihydroxyphenylalanine (Dopa) and the oxidation of dopa to dopaquinone. In the presence of L-cysteine, dopaquinone rapidly combines with the thiol group to form cysteinyldopas, which undergo nonen-zymatic conversion and polymerization to pheomelanin via benzothiazine intermediates. In the absence of thiol groups, dopaquinone very rapidly undergoes conversion to dopachrome, which is transformed to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) by dopachrome tautomerase. Alternatively, dopachrome is converted nonenzymatically to 5,6-dihydroxyindole (DHI). Oxidation of DHICA and DHI to the corresponding quinones and subsequent polymerization leads to eumelanins. It is still questionable if Ty is involved in this step. 

Peptide-bond formation and transamination are the most general reactions of the standard amino acids, but individual amino acids often undergo reactions of more limited scope. One of the biosynthetic pathways to L-tyrosine is oxidation of L-phenylalanine. An arene oxide is an intermediate. 

Table I presents data from McFarlane al, (8) showing that the multi-step oxidation of L-tyroslne to p-hydroxymandelonltrlle requires only 02 and a source of reducing power, most effectively supplied by an NADFH generating system. The table also shows that some of the L-tyroslne Is converted to p-hydroxyphenylacetaldoxime (aldoxime) as well as a trace of p-hydroxyphenylacetonltrlle (nitrile). The production of the aldoxime and nitrile In this experiment was the first Indication that the microsomal preparation from sorghum might constitute an organized enzyme entity Involved In the synthesis of dhurrln. If this were true, it should be possible to demonstrate each individual step of the reaction sequence between tyrosine and p-hydroxymandelontrlle.

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