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Complex molecular regulation of tyrosine hydroxylase

  • Translational Neurosciences - Review article
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Abstract

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is strictly controlled by several interrelated regulatory mechanisms. Enzyme synthesis is controlled by epigenetic factors, transcription factors, and mRNA levels. Enzyme activity is regulated by end-product feedback inhibition. Phosphorylation of the enzyme is catalyzed by several protein kinases and dephosphorylation is mediated by two protein phosphatases that establish a sensitive process for regulating enzyme activity on a minute-to-minute basis. Interactions between tyrosine hydroxylase and other proteins introduce additional layers to the already tightly controlled production of catecholamines. Tyrosine hydroxylase degradation by the ubiquitin–proteasome coupled pathway represents yet another mechanism of regulation. Here, we revisit the myriad mechanisms that regulate tyrosine hydroxylase expression and activity and highlight their physiological importance in the control of catecholamine biosynthesis.

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Acknowledgments

This work was supported by grants from the National Institutes of Health (GM38931) and the Penn State Institute for Personalized Medicine (04-017-52 HY 8A1HO; under a grant from the Pennsylvania Department of Health using Tobacco CURE Funds). The PA Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions.

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  1. Department of Pharmacology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033-0850, USA

    Izel Tekin, Nurgul Carkaci-Salli & Kent E. Vrana

  2. Blue Ridge Institute for Medical Research, Horse Shoe, NC, USA

    Robert Roskoski Jr.

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  1. Izel Tekin
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  2. Robert Roskoski Jr.
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Correspondence to Kent E. Vrana.

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I. Tekin and R. Roskoski Jr. have contributed equally to preparation of this manuscript.

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Tekin, I., Roskoski, R., Carkaci-Salli, N. et al. Complex molecular regulation of tyrosine hydroxylase. J Neural Transm 121, 1451–1481 (2014). https://doi.org/10.1007/s00702-014-1238-7

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