Abstract
THERE is much evidence that catecholamines may act as synaptic transmitters in the mammalian brain1. Enzymatic activities necessary for the synthesis of catecholamines have been located in central neurones1 and it is generally believed that tyrosine hydroxylase2 is the rate limiting enzyme in brain as well as peripheral tissues containing catecholamines3. While it is clear that tyrosine can serve as a precursor of catecholamine synthesis in the brain1, 3, 4, the significance of phenylalanine is problematic. It was believed that the mammalian brain is devoid of enzymatic activity necessary to convert phenylalanine to tyrosine6, 7, while liver is known to be rich in the enzyme phenylalanine hydroxylase8. The earlier attempts to demonstrate hydroxylation of phenylalanine in brain tissue may have been unsuccessful due to methodological problems9. Recent evidence suggests that tyrosine hydroxylase prepared from peripheral sympathetically innervated tissues or from brain can hydroxylate either phenylalanine or tyrosine9. Initially, the rate of hydroxylation of phenylalanine by tyrosine hydroxylase was thought to be as little as 5% that of tyrosine9. It has been found recently, however, that structural variations in the pteridine cofactor present in the incubation mixture lead to striking changes in the ability of partially purified tyrosine hydroxylase from bovine adrenal medulla to hydroxylate phenylalanine10. Thus, tetrahydrobiopterin allowed the hydroxylation of phenylalanine to proceed at least as rapidly as that of tyrosine or faster10. As the structure of the endogenous pteridine cofactor of tyrosine hydroxylase is not known, it is possible that synthesis of catecholamines from phenylalanine as well as tyrosine could occur in intact neuronal tissues. Evidence has been presented that after the injection of large quantities of 14C-phenylalanine into the lateral ventricle of the rat brain, small amounts of labelled tyrosine and traces of newly synthesized catecholamines were detected in brain tissues, giving qualitative evidence that catecholamines may be synthesized in brain from phenylalanine in vivo11.
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KAROBATH, M., BALDESSARINI, R. Formation of Catechol Compounds from Phenylalanine and Tyrosine with Isolated Nerve Endings. Nature New Biology 236, 206–208 (1972). https://doi.org/10.1038/newbio236206a0
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DOI: https://doi.org/10.1038/newbio236206a0
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