Tetrahydrobiopterin and

Fig. 2. Biosynthetic pathway for epinephrine, norepinephrine, and dopamine. The enzymes cataly2ing the reaction are (1) tyrosine hydroxylase (TH), tetrahydrobiopterin and O2 are also involved (2) dopa decarboxylase (DDC) with pyridoxal phosphate (3) dopamine-P-oxidase (DBH) with ascorbate, O2 in the adrenal medulla, brain, and peripheral nerves and (4) phenethanolamine A/-methyltransferase (PNMT) with. Cadenosylmethionine in the adrenal...

Murata S, Ichinose H, Urano F (2007) Tetrahydrobiopterin and Related Biologically Important Pterins. 8 127-171... 

Hevel, J. M., and Marietta, M. A. (1992). Macrophage nitric oxide synthase Relationship between enzyme-bound tetrahydrobiopterin and synthase activity. Biochemistry 31, 7160-7165. 

Nitroindazole Competitive inhibitor, binds both tetrahydrobiopterin and arginine-binding sites in NOS Partially selective for NOS-1 in vivo... 

Blau N, Thony B, Cotton RGH, Hyland (2001) Disorders of tetrahydrobiopterin and related biogenic amines. In Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein (eds)The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, New York, pp 1725-1776... 

Blau N, Thony B, Spada M, Ponzone A (1996) Tetrahydrobiopterin and inherited hyperphe-nylalaninemias. Turk J Pediatr 38 19-35... 

Hyland K, Heales SJ. (1993) Tetrahydrobiopterin and quinonoid dihydrobiopterin concentrations in CSF from patients with dihydropteridine reductase deficiency. J Inherit Metab Dis 16 608-610... 

Tyrosine is converted to dopa by the rate-limiting enzyme tyrosine hydroxylase, which requires tetrahydrobiopterin, and is inhibited by a-methyltyrosine. Dopa is decarboxylated to dopamine by L-aromatic amino acid decarboxylase, which requires pyridoxal phosphate (vitamin B6) as a coenzyme. Carbidopa, which is used with levodopa in the treatment of parkinsonism, inhibits this enzyme. Dopamine is converted to norepinephrine by dopamine P-hydroxylase, which requires ascorbic acid (vitamin C), and is inhibited by diethyldithiocarbamate. Norepinephrine is converted to epinephrine by phenylethanolamine A -methyltransferase (PNMT), requiring S-adeno-sylmethionine. The activity of PNMT is stimulated by corticosteroids. 

A convenient HPLC technique known as the Fukushima-Nixon method has been widely used for selective analyses of tetrahydrobiopterin and tetrahy-droneopterin in biological samples [49]. This method allows the estimation of concentrations of tetrahydropterins based on difference in the concentrations of the corresponding aromatic pterins in the samples, which are prepared in situ by treatment with iodine under acidic and basic conditions. The Fukushima-Nixon method does not require special techniques or equipment for the chemical reaction the sample is simply subjected to oxidation just before its injection into the HPLC column. For example, tetrahydrobiopterin (43) was selectively oxidized to biopterin (30) by iodine in the presence of... 

The fifth chapter, Tetrahydrobiopterin and Related Biologically Important Pterins by Shizuaki Murata, Hiroshi Ichinose and Fumi Urano, describes a modern aspect of pteridine chemistry and biochemistry. Pteridine derivatives play a very important role in the biosynthesis of amino acids, nucleic acids, neurotransmitters and nitrogenmonooxides, and metabolism of purine and aromatic amino acids. Some pteridines are used in chemotherapy and for the diagnosis of various diseases. From these points of view, this article will attract considerable attention from medicinal and pharmaceutical chemists, and also heterocyclic chemists and biochemists. 

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