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The Role of Tyrosine Hydroxylase in the Regulation of Catecholamine Synthesis

  • Chapter
Catecholamines II

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 90 / 2))

Abstract

Tyrosine-3-monoxygenase (EC 1.14.16.2) (tyrosine hydroxylase) is the rate limiting enzyme in the pathway for the synthesis of catecholamines. This enzyme was first demonstrated in bovine adrenal medulla (Nagatsu et al. 1964 a; Brenneman and Kaufman 1964). Tyrosine hydroxylase is a mixed function oxidase, requiring molecular oxygen (Daly et al. 1968) and a reduced pterin (Nagatsu et al. 1964a; Brenneman and Kaufman 1964) as cosubstrates. The putative natural pterin cosubstrate is believed to be tetrahydrobiopterin and was first demonstrated in adrenal medulla cells (Lloyd and Weiner 1971). The cofactor is also present in brain tissue and the concentration of tetrahydrobiopterin in various brain regions is correlated with the distribution of catecholamines (Gal et al. 1976; Bullard et al. 1978; Levine et al. 1979; Mandell et al. 1980). Biopterin can be syntesized from guanosine in mouse neuroblastoma clones (Buff and Dairman 1974) and from guanosine triphosphate (GTP) in rat brain (Gal and Sherman 1976). Dihydropteridine reductase, the enzyme that catalyzes the reduction of 7,8-dihydropterins to the active 5,6,7,8-tetrahydroform, has been demonstrated in sheep liver (Kaufman 1964; Nielsen et al.1969; Craine et al. 1972), beef adrenal medulla (Musacchio 1969; Musacchio et al. 1971) and brain (Turner et al. 1974; Spector et al. 1977). The enzyme requires a reduced pyridine nucleotide for activity. Either NADH or NADPH serves as a cofactor for dihydropteridine reductase, but the former pyridine nucleotide exhibits a higher affinity for the enzyme (Nielsen et al. 1969; Craine et al. 1972).

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  1. J. M. Masserano
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  2. P. R. Vulliet
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  3. A. W. Tank
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  4. N. Weiner
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Editors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, D-8700, Würzburg, Germany

    U. Trendelenburg (Professor Dr.) (Professor Dr.)

  2. Department of Pharmacology, Colorado University, Medical Center, 4200 East Ninth Street, 80262, Denver, CO, USA

    N. Weiner (Professor Dr.) (Professor Dr.)

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Masserano, J.M., Vulliet, P.R., Tank, A.W., Weiner, N. (1989). The Role of Tyrosine Hydroxylase in the Regulation of Catecholamine Synthesis. In: Trendelenburg, U., Weiner, N. (eds) Catecholamines II. Handbook of Experimental Pharmacology, vol 90 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73551-6_11

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