Tyrosine cytochrome

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Scheme 10.8 Biosynthesis of epothilone. Individual PKS domains are represented as circles and individual NRPS domains as hexagons. Acyl carrier proteins (ACPs) and thiola-tion domains (T) are posttranslationally modified by a phos-phopantetheinyl group to which the biosynthetic intermediates are covalently bound throughout the chain assembly. The thioesterase domain (TE) cyclizes the fully assembled carbon chain to give the 16-membered lactone. Following dehydration of Cl 2—Cl 3 to give epothilones C and D, the final step in epothilone biosynthesis is the epoxidation of the C12=C13 double bond by the cytochrome P450 enzyme P450epol<. KS ketosyn-thase KS(Y) active-site tyrosine mutant of KS AT acyltransfer-ase C condensation domain A adenylation domain ...

Because LCEC had its initial impact in neurochemical analysis, it is not, surprising that many of the early enzyme-linked electrochemical methods are of neurologically important enzymes. Many of the enzymes involved in catecholamine metabolism have been determined by electrochemical means. Phenylalanine hydroxylase activity has been determined by el trochemicaUy monitoring the conversion of tetrahydro-biopterin to dihydrobiopterin Another monooxygenase, tyrosine hydroxylase, has been determined by detecting the DOPA produced by the enzymatic reaction Formation of DOPA has also been monitored electrochemically to determine the activity of L-aromatic amino acid decarboxylase Other enzymes involved in catecholamine metabolism which have been determined electrochemically include dopamine-p-hydroxylase phenylethanolamine-N-methyltransferase and catechol-O-methyltransferase . Electrochemical detection of DOPA has also been used to determine the activity of y-glutamyltranspeptidase The cytochrome P-450 enzyme system has been studied by observing the conversion of benzene to phenol and subsequently to hydroquinone and catechol... 

Rogers MS, Dooley DM. 2001. Posttranslationally modihed tyrosines from galactose oxidase and cytochrome c oxidase. Adv Protein Chem 58 387. 

KOCH, B.M., SIBBESEN, O., HALKIER, B.A., SVENDSEN, I., M0LLER, B.L., The primary sequence of cytochrome P450tyr, the multifunctional N-hydroxylase catalyzing the conversion of L-tyrosine to /7-hydroxyphenylacetaldehyde oxime in the biosynthesis of the cyanogenic glucoside dhurrin in Sorghum bicolor (L.) Moench, Arch. Biochem. Biophys., 1995,323, 177-186. 

In microsomes from Sinapis alba L.,33,34 Tropaeolum majus L.,35,36 and Carica papaya L.,37 the aromatic amino acids (tyrosine and phenylalanine) have been shown to be converted to the corresponding oximes by cytochrome P450-dependent monooxygenases. The conversion of tyrosine to the corresponding oxime in microsomes from S. alba was approximately 1000 fold lower than in microsomes from the cyanogenic sorghum.33 This made a biochemical approach for the isolation... 

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). 

Fe3+ also shows a strong affinity for the oxygen donor atoms of carboxylates as well as the phenoxide of tyrosine. Like cysteine, the sulfur ligand of methionine is often found bound to iron, for example in electron-transfer haemoproteins such as cytochrome c. 

Fe atoms. It had been anticipated that the c-type cytochrome center would have His/Met coordination, but His/His is observed. The former is the more usual coordination, especially at the high potential end E° > +200 mV) ofthe typical bacterial electron transfer chain to which the nitrite reductase is connected (Fig. 2) (7). The second curious feature is that the di heme iron is also six-coordinate thus, the enzyme does not offer a substrate-binding site at either heme. In addition to an expected axial histidine ligand there was an axial tyrosine (residue 25) ligand to the d heme (Fig. 4a). Each monomer is organized into two domains. 

His/Met and the di heme ligation is probably hydroxide rather that tyrosine. Thus, solution studies, as well as analyses of primary sequences, confirm that cytochrome cd from different sources can have different ligands to the heme irons. 

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