GTP Cyclohydrolase I Gene Expression and Catecholamine Synthesis

  • Gregory Kapatos
  • Kei Hirayama
Part of the Advances in Behavioral Biology book series (ABBI, volume 53)

Abstract

The reduced pteridine 5,6,7,8-tetrahydrobiopterin (BH4) is the essential cofactor for the family of pterin-dependent monooxygenases that includes tyrosine (TH), tryptophan (TPH) and phenylalanine hydroxylase, the rate-limiting enzymes in the synthesis of the monoamine (MA) neurotransmitters dopamine (DA), norepinephrine and serotonin (5-HT) and the detoxification of L-phenylalanine, respectively (Kaufman, 1974). BH4 serves as an electron donor in these enzyme reactions. GTP cyclohydrolase I (GTPCH) catalyzes the first and rate-limiting step in de novo BH4 biosynthesis, the formation of the first pterin intermediate, D-erythro-7,8-dihydroneopterin triphosphate, from GTP (Nichol et al., 1985). Within the brain GTPCH mRNA (Hirayama et al., 1993) and protein (Nagatsu et. al., 1997; Dassesse et. al., 1997) can only be detected within MA neuronal cell bodies. GTPCH protein is transported to the MA nerve terminals, indicating that BH4 is synthesized at its primary site of action (Levine et al., 1981). The rate of BH4 synthesis actually exceeds that of the MA neurotransmitters, with 25% of the intracellular pool being synthesized each hour (Kapatos, 1990). BH4 levels within DA nerve terminals are subsaturating for TH (Kettler et al., 1974) while BH4 levels within 5-HT nerve endings saturate TPH (Wolf et al., 1991). This distinction based upon neurotransmitter phenotype may be important clinically (see below) and presumably is due to the low levels of GTPCH mRNA (Lentz and Kapatos, 1996) and GTPCH protein (Hirayama and Kapatos, 1998) that are expressed within nigrostriatal DA neurons.

Keywords

Vasoactive Intestinal Peptide Superior Cervical Ganglion Neurotransmitter Phenotype Tyrosine Hydroxylation Basal Ganglion Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Gregory Kapatos
    • 1
  • Kei Hirayama
    • 1
  1. 1.Department of Psychiatry and Behavioral Neurosciences and Center for Molecular Medicine and GeneticsWayne State University School of MedicineDetroitUSA

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