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Down-regulation of GTP cyclohydrolase I and tetrahydrobiopterin by melatonin
1Department of Biochemistry, University of Ulsan College of Medicine, Seoul, Korea.
Abstract:
Tetrahydrobiopterin (BH4) is spontaneously released and extracellularly exerts a toxic effect preferentially on catecholamine cells. Its synthesis rate is mainly determined by the activity of the enzyme GTP cyclohydrolase I (GTPCH). In the present study, role of melatonin BH4 synthesis was determined using the catecholaminergic CATH.a cells. The neurohormone dose-dependently reduced both intracellular and extracellular BH4 levels. This was due to both direct inhibition of catalytic activity of the existing GTPCH enzyme and down-regulation of GTPCH gene expression. Thus, melatonin is an effective down-regulator of BH4 synthesis and is a potential therapeutic agent with which to control BH4 level in aberrant conditions where it may rise to a toxic level.
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