0891-5849/92 $5.00 + .00 Copyright © 1992 PergamonPress Ltd.
BIOCHEMICAL AND TOXICOLOGICAL PROPERTIES OF OXIDATION PRODUCTS OF CATECHOLAMINES THE
ALBERTO BINDOLI,* MARIA PIA RIGOBELLO, t and DAVID J. DEEBLE* *Centro Studio Fisiologia Mitocondriale, CNR, Padova, Italy;*Dipartimento di Chimica Biologica, Universit~ di Padova, Padova, Italy; and *The North East Wales Institute of Higher Education, Faculty of Science and Innovation, Deeside, Clwyd, U.K. (Received 26 November 1991;Revised and Accepted 1 April 1992) Abstract--The normal catabolism of catecholamines proceeds through enzymatic pathways (monoaminooxidase, catechol-omethyltransferase, andphenolsulphotransferase). In addition, nonenzymatic oxidative pathways might take place since catechols are readily oxidized. In this review article, the pathways of formation of the oxidation products ofcatecholamines and their reactions are described. The interactions of these products with different biological systems and their toxicity are examined. Among the reactions known to occur is that withsulthydryls, which results in either a covalently linked adduct or disulfide production. Another interesting pathway to toxicity involves the oxidation of these eatecholamine products by oxygen, with the formation of damaging oxygen-derived species. The action of the oxidation products ofcatecholamines is outlined, with special attention to the nervous and cardiac systems. Keywords--Adrenochrome,Aminochromes, Cardiotoxicity, Catecholamine oxidation, Free radicals, Neurotoxicity, Orthoquinones, Redox cycling, Sulfhydryl groups
Natural quinones occur as benzo-, naphtho-, and anthraquinones.~'2 Ubiquinones are a family of ubiquitous lipid-soluble benzoquinones that can be reversibly oxidized to hydroquinone and consequently act in electron transport in mitochondria. Plastoquinonesare benzoquinones involved in the electron transport chain of chloroplasts. Vitamins K are another important group of para-quinones characterized by the naphthoquinone ring. They occur naturally as two families: phylloquinones (vitamin K~) and menaquinones (vitamin K2). Menadione (vitamin K3) is a synthetic compound lacking the isoprenoid sidechain but still bearing vitamin activity. Quinonesare also present in p o l l u t a n t s , 3'4 essentially as polyaromatic hydrocarbons, and in several antineoplastic drugs, s'6 Several excellent reviews 1'2'7'8 deal with their functional, toxicological, and antitumor properties, and the reader is referred to them for detailed information. Quinones can also come from other endogenous
Address correspondence to: Dr. A. Bindoli, Dipartimento diChimica Biologiea, Via Trieste 75, 35121 Padova, Italy. 391
sources, such as the oxidative metabolism of the catecholamines. In Figure 1 the structural formulae of some catecholamines and derivatives are reported. Dopa, dopamine, adrenaline, and noradrenaline can be converted to their corresponding quinones. On cyclization, these give rise to the formation of aminochromes and related compounds,such as aminolutins and dihydroxyindoles, which eventually lead to the well-known polymeric products called melanins. The present review focuses on the chemical properties and the biological effects of the intermediate products formed during the complex and still incompletely defined processes occurring in the oxidative pathway of the catecholamines.
THE OXIDATIVE PATHWAY OF THE CATECHOLAMINESRedox chem&tryof catecholamines
Catecholamines, as is apparent from their name, contain the catechol moiety as an integral part of their structure. Many of the chemical properties of catecholamines are due to the presence of the catechol group; this is certainly the case regarding oxidation reactions, which are a prime concern of this review. A