Nature 252, 719 - 720 (20 December 1974); doi:10.1038/252719a0

Tyrosine-dependent increase of tyrosine hydroxylase in neuroblastoma cells

TOM LLOYD^* & XANDRA O. BREAKEFIELD^†

^*Laboratory of Neurochemistry, National Institute of Mental Health, Betheseda, Maryland 20014
^†Laboratory of Biochemical Genetics, National Heart and Lung Institute, Bethesda, Maryland 20014 and Department of Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510

TYROSINE hydroxylase (tyrosine-3-monooxygenase), presumably the rate-limiting enzyme in the biosynthesis of the adrenergic transmitters dopamine and noradrenaline^1,2, catalyses the hydroxylation of both phenylalanine and tyrosine^3,4. This property has been exploited for the selection of adrenergic-like mouse neuroblastoma cells⁵, which have high tyrosine hydroxylase activity and can grow in the absence of tyrosine because they can convert sufficient phenylalanine to tyrosine for cell growth. N1E-115 is such a neuroblastoma clone^5,6 and we have now found that, when the amount of tyrosine in the medium is increased, there is an increase in the amount of tyrosine hydroxylase in N1E-115 cells. Modification of the amount of this rate-limiting enzyme by its substrate concentration may play a fundamental role in the regulation of the biosynthesis of catecholamines.

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