Non-equilibrium behavior of some brain enzyme and receptor systems.

Abstract

The previous article in this review dealing with the regulatory properties of brain tyrosine (TOH) and tryptophan hydroxylase (TPOH) systems (1 ) empha­ sized (a) multidimensional ity: almost all the components present under phys ­ iological and assay conditions, ranging from electromagnetic fields through hydrophobic ligands to reducing equivalents, influence in one way or another the rate functions representing catalytic activities; (b) nonlinearity: critical zones of ligand concentration, curvilinear, even intermittent amount-effect functions, and inconsistencies among results depending on small differences in parameter values are consonant with the prominent role of cooperative interac­ tions among the many stated and unstated dimensions (coordinates) regulating catalytic systems; (c) conformational instability: in the protein macromolecular components of TOH and TPOH, conformational instabilities are evidenced by 20 years offailure to purify the enzyme proteins in amounts useful for systemat­ ic extensive kinetic characterization , by their extreme friability under condi­ tions of storage, by their multiplicity of reported molecular weigh ts and kinetic constants, and by their markedly increased ease of denaturation and precipita­ tion after the removal of components from their normal milieu by dialysis and enrichment procedures. That article expressed hope that a multivariate approach to studies of TOH and TPOH regulation could be developed to allow data reduction through pattern analysis in place of one-or two-variable kinetic experiments and quantification by Michaelis or Hill constants (1 ). This review updates the 1978 one with respect to research on the regulatory properties of TOH and TPOH as reported in the literature through early 1983 with the exception of the cyclic nucleotide-prote in phosphorylati on schemata (recently involving calmodulin), the current status of which is reviewed else