Biopterins

The fluorescent compounds that were isolated from Euglena gracilis have been given the structures 3-6, one of which stimulated ferredoxin-dependent oxygen reduction by isolating 

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All NOS isoforms utilize L-arginine as the substrate, and molecular oxygen and reduced nicotinamide adenine dinucleotide phosphate (NADPH) as cosubstrates. Flavin adenine dinucleotide (FMN), flavin mononucleotide (FAD), and (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) are cofactors of the enzyme. All NOS isoforms contain heme and bind calmodulin. In nNOS and eNOS,... 

Phenylalanine is hydroxylated to tyrosine and then sequentially to 4-hydroxyphenyl-pyruvate and by dioxygenation and rearrangement to 2,5-dihydroxyphenylpyruvate (Figure 3.16) (Arias-Barrau et al. 2004). Hydroxylation involves 6,7-dimethyltetrahydro-biopterin that is converted into the 4a-carbinolamine (Song et al. 1999). Copper is not a component of the active enzyme, although there is some disagreement on whether or not Fe is involved in the reaction for the hydroxylase from Chromobacterium violaceum (Chen and Frey 1998). 

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... 

In view of the importance in biochemical processes of pteridines such as folic acid, methotrexate, L-biopterin, and leucettidine <1996CHEC-II(7)679>, synthetic routes to fused pteridines continue to occupy considerable attention. Imidazo-fused pteridines have now been prepared from 3-aminopyrazine-2-carboxamides via carbodiimide intermediates. If the amido-nitrogen in the starting compound is further substituted, as in the scheme, the... 

A strategy has been described for the synthesis of 2-ethyIthio-6-(3-hydroxy-1,2-0-isopropylidenepropyl)pteridin-4(3//)-one 90 which can be used as a useful intermediate for the conversion of neopterin to biopterin. Diaminopyrimidinone 86 reacts with D-arabinose phenylhydrazone 87, the obtained diastereomeric mixture 88 is converted into its isopropylidene derivative 89 which under oxidation conditions yields 90 <00H(53)1551>. 

AG, (total) in Table 3 and Equation 1. DHFR.NADPH.methotrexate coordinates (ref. 35). 1 DHFR.-methotrexate coordinates (ref. 36). DHFR.NADPt.folate coordinates (ref. 37). h DHFR.NADP. biopterin coordinates (ref. 40). DHFR folate coordinates (ref. 41). 

Tyrosine hydroxylase is the rate-limiting enzyme for the biosynthesis of catecholamines. Tyrosine hydroxylase (TH) is found in all cells that synthesize catecholamines and is a mixed-function oxidase that uses molecular oxygen and tyrosine as its substrates and biopterin as its cofactor [1], TH is a homotetramer, each subunit of which has a molecular weight of approximately 60,000. It catalyzes the addition of a hydroxyl group to the meta position of tyrosine, thus forming 3,4-dihydroxy-L-phenylalanine (l-DOPA). 

Rarely, phenylketonuria results from a defect in the metabolism of biopterin, a cofactor for the phenylalanine hydroxylase pathway 673... 

PKU) phenylalanine hydroxylase. In care cases, defect of biopterin metabolism (Fig. 40-3 reaction 1) children. Avoidable with early institution of diet therapy. Prognosis less favorable in PKU secondary to defect of biopterin metabolism Carbidopa... 

FIGURE 40-2 The phenylalanine hydroxylase (PAH) pathway. Phenylketonuria usually is caused by a congenital deficiency of PAH (reaction 1), but it also can result from defects in the metabolism of biopterin, which is a cofactor for the hydroxylase. Enzymes (1) Phenylalanine hydroxylase (2) Dihydropteridine reductase (3) GTP cyclohydrolase (4) 6-pyruvoyltetrahydrobiopterin synthase. BH4, tetrahydrobiopterin DEDT, o-erythro-dihydroneopterin triphosphate QH2, dihydrobiopterin. 

Rarely, phenylketonuria results from a defect in the metabolism of biopterin, a cofactor for the phenylalanine hydroxylase pathway. The electron donor for phenylalanine hydroxylase is tetrahydrobiopterin (BH4), which transfers electrons to molecular oxygen to form tyrosine and dihydrobiopterin (QH2 Fig. 40-2 reaction 2). BH4 is regenerated from QH2 in an NADH-dependent reaction that is catalyzed by dihydropteridine reductase (DHPR), which is widely distributed. In the brain, this... 

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