Modulation of tryptophan hydroxylase stability: a possible mechanism for monoamine enzyme regulation
The instability of brain tryptophan hydroxylase (tryptophan5-monooxygenase: E.C.18.104.22.168), the rate-limiting enzyme in the biosynthesis of serotonin, has been a bane to those workers who have attempted to study this enzyme in both crude and enriched preparations. At present no satisfactory purification procedure exists that yields stable enzyme in relatively abundant amounts. As a consequence, much remains to be understood about this important regulatory enzyme. Regarding the lability of tryptophan hydroxylase (TPOH) less as an impediment to our understanding of serotonergic systems and more as a source of understanding, I have begun a study of TPOH that focuses on the stability properties of this enzyme. I review here some of the salient features of this work, which suggest that stability may be yet another regulatable property of tryptophan hydroxylase and may represent a hitherto unrecognized but important mechanism for the control of transmitter levels in the neuron.
KeywordsTyrosine Hydroxylase Enzyme Preparation Tryptophan Hydroxylase Transmitter Level Activate Tyrosine Hydroxylase
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- Ballard, F.J. (1980). Degradation of enzymes. In Principles of of Metabolic Control in Mammalian Systems, (eds. Herman, R.H., Cohn, R.M., and McNamara, P.D.), Plenum Press, New York.Google Scholar
- Banik, N.L., Powers, J.M., Smith, K., and Hogan, E.L. (1979). Ca+2-activated neutral proteinase in normal and traumatized spinal cord. Soc. Neurosci. Abs. 4, 396.Google Scholar
- Bond, J. (1975). Correlations between in vivo turnover and in vitro inactivation of rat liver enzymes. In Intracellular Protein Turnover, (eds. Schimke, R.T. and Katunuma, N.), Academic Press, New York.Google Scholar
- Switzer, R.L. (1977). The inactivation of microbrial enzymes in vivo. Ann. Rev. Biochem. 31, 135–157.Google Scholar
- Vitto, A. and Gaertner, F.H. (1978). Proteolytic inactivation and coordinate protection of the arom enzyme conjugate of Neurospora. In Limited Proteolysis in Microorganisms (eds. Cohen, G.N. and Holzer, H.), Fogarty Internat’l Conf., DHEW Publ. No. (NIH) 79–1591, Govt. Printing Off., Washington, D.C.Google Scholar
- Vitto, A., Cole, K.W., and Gaertner, F.H. (1978). Proteolytic inactivation of a pentafunctional enzyme conjugate: coordinate protection by the first substrate. Biochem. Biophys. Res. Commun. 82, 977–981.Google Scholar
- Vitto, A. and Mandell, A.J. (1979). Calcium-dependent activation, stabilization, and destabilization of tryptophan hydroxylase from rat midbrain. Soc. Neurosci. Abs. 4, 419.Google Scholar
- Vitto, A., Cole, K.W., and Gaertner, F.H. (1979). Proteolysis of a multienzyme conjugate: a possible mechanism for breaking a metabolic channel. In Cell Compartmentation and Metabolic Channeling, (eds. Nover, L., Lynen, F., and Mothes, D.), Elsevier/North-Holland, Amsterdam.Google Scholar
- Vitto, A., and Mandell, A.J. (1981). Stability properties of activated tryptophan hydroxylase from rat midbrain. J. Neurochem. 36, in press.Google Scholar