Catecholamine metabolism revisited: From neurochemistry to integrative physiology and pathophysiology

After a previous overview published more than 20 years ago, key aspects of catecholamine metabolism remain incompletely understood by physiologists. Meanwhile, the repertoire of assayable catecholamine-related compounds has expanded. Moreover, alterations in catecholamine metabolic patterns associated with physiological changes, drug effects, and pathophysiological states were not covered; and biochemical phenotyping via kinetic models now makes it possible to elucidate physiology and pathophysiology in individuals. Accordingly, this review starts with the inventory of catecholamine-related compounds and the three main peripheral catecholamine systems (sympathoneuronal, adrenomedullary, and autocrine/paracrine). Catecholamine systems contribute to virtually every organ function, behavior, and emotional state, and we describe situations where alterations in those systems exert syndromic pathophysiological effects. We then describe the relationships of catecholamine metabolic patterns to synthesis, storage, release, reuptake, and intra-neuronal and extra-neuronal metabolism of catecholamines; effects of physiological processes and drugs on those patterns; and catecholamine biochemical patterns associated with pathophysiologic states. We provide examples of how detailed, comprehensive knowledge acquired over the past half century has led to computational models for estimating the rates of processes that characterize specific physiological changes and some clinical disorders. The integrative physiological approach presented here has the potential to pinpoint specific functional abnormalities within catecholaminergic cells and thereby rationalize novel, testable treatment and prevention strategies.