Calcium, cofactor, and propranolol induced changes in the kinetic variations of rat raphe tryptophan hydroxylase activity
In the presence of physiological concentrations of substrate and cofactor, the kinetics of tryptophan hydroxylase (TPOH) activity over increasing concentrations of tetrahydrobiopterin (BH4) demonstrate nonlinearity, yielding multiple quasi-regular zones of zero slope in their velocity functions (Knapp & Mandell, 1979, 1981) similar to the “intermediary plateau regions” in substrate saturation curves reported by Teipel and Koshland (1969). We have shown that calcium, known to reduce the Km of TPOH for both cofactor and substrate (Knapp et al., 1975; Boadle-Biber, 1975), shifts the reiterative rat raphe cofactor velocity curve to the left. Using the tools of variational analysis and fine-grained kinetic studies, we have now quantified the cofactor-dependent fluctuations of TPOH velocity in the presence of physiological concentrations of substrate and cofactor, demonstrating that cofactor-dependent as well as time-dependent kinetic functions of raphe TPOH are reiterative, manifesting intermediary saturation plateaus over cofactor and multiple characteristic power spectral peaks over time.
KeywordsLithium Tyrosine Serotonin Tryptophan Autocorrelation
Unable to display preview. Download preview PDF.
- Feher, G. and Weissman, M. (1973). Fluctuation spectroscopy: Determination of chemical reaction kinetics from the frequency spectrum of fluctuations. Proc. Natl. Acad. Sci. USA, 70, 870–875.Google Scholar
- Knapp, S. and Mandell, A.J. (1980). Lithium and chlorimipramine differentially alter bilateral asymmetry in mesostriatal serotonin metabolites and kinetic conformations of midbrain tryptophan hydroxylase with respect to tetrahydrobiopterin cofactor. Neuropharmacology, 19, 1–7.CrossRefPubMedGoogle Scholar
- Knapp, S. and Mandell, A.J. (1981). Mouse midbrain tryptophan hydroxylase: Strain differences in variational properties. J. Physiologie (Paris), 77, in press.Google Scholar
- Knapp, S., Mandell, A.J., and Bullard, W.P. (1975). Calcium activation of brain tryptophan hydroxylase. Life Sci., 16, 1583–1594.Google Scholar
- Mandell, A.J. and Russo, P.V. (1981). Striatal tyrosine hydroxylase: Multiple conformational kinetic oscillators and product concentration frequencies. J. Neurosci. 1(4), in press.Google Scholar
- Moe, G.K. and Abildskow, J.A. (1975). Antiarrhythmic drugs. In: The Pharmacological Basis of Therapeutics (eds. L.S. Goodman and A. Gilman), pp. 683–704. Macmillan, N.Y.Google Scholar
- Prigogine, I. (1965). Non-Equilibrium Thermodynamics, Variational Techniques and Stability. Univ. of Chicago Press, Chicago.Google Scholar