Stabilization of Central Biosynthetic Enzyme Dynamics Against Cholinergic Perturbation.
Final rept. 1 Jul 83-30 Jun 86,
CALIFORNIA UNIV SAN DIEGO LA JOLLA DEPT OF PSYCHIATRY
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Measure theoretic techniques for the evaluation of enzyme kinetic stability have been developed. Motivated by the phenomena of reversible and irreversible aging in cholinergic peripheral and central neutral enzymes following neurotoxic exposure and the toxic effects of conventional antagonists, the basis for an alternative strategy was established the delay of irreversibility through understanding the dynamics of phase transitions in brain enzymes. A battery of quantifiers with which to examine time series in biological observables have been developed. Loss of entropy spells dysfunction in signal-sensitive biological dynamics. In the case of rate-limiting enzymes in the synthesis of biogenic amine transmitters, treatments and conditions that retarded emergent periodicity in the time-dependent or substrateligand dependent dynamics tended to prevent the desensitized state.