Lithium and chlorimipramine differentially alter the stability properties of tryptophan hydroxylase as seen in allosteric and scattering kinetics.
Compared to control, both lithium and chlorimipramine (CMI) slow the frequency of variation in tryptophan hydroxylase (TPOH) velocity functions measured across increasing (nearly physiological) cofactor concentrations or across continuous (long residence) time. The common effect appears to be generated by different statistical mechanisms in view of the diverse patterns observed when, for multiple 60-point experiments for each condition, mean frequencies were plotted against mean amplitudes of variation: lithium constricted the frequencies over a range of amplitudes; CMI fixed amplitude across the range of frequencies. Initial rate, short residence time experiments suggest that at the micromolecular level, before the emergence of time-dependent macro-kinetic organization as seen in the long residence time assays, lithium may uncouple the elementary constituents of the system, allowing subsequent phase gathering and emergent stability around a statistically dominant frequency, whereas CMI may augment coupling, leading to unstable complexity in the population dynamics. The relationship between these effects and allosteric kinetic functions is discussed.
D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D002997:Clomipramine / Q000494:pharmacology*; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D008094:Lithium; D014365:Tryptophan Hydroxylase; D002997:Clomipramine