CATABOLISM OF 5-AMINOLEVULINIC ACID TO CO2 BY RAT-LIVER MITOCHONDRIA

5-Aminolevulinic acid (ALA), the heme precursor accumulated in plasma and several organs of carriers of acute intermittent porphyria, heredi tary tyrosinemia, and saturnism, was previously shown to yield reactiv e oxygen species upon metal-catalyzed aerobic oxidation and to cause t he in vivo and in vitro impairment of rat liver mitochondrial function s. We have studied the uptake and catabolism of [5-C-14]ALA to CO2 by isolated rat liver mitochondria (RLM) with the aim of determining whet her possible ALA-driven oxidative injury to mitochondria can also occu r into the matrix. Using silicone oil centrifugation of [5-C-14]ALA-tr eated RLM, ALA was found to partition evenly into the intra- and extra matrix space of the mitochondrial preparations. The yield of evolved ( CO2)-C-14 is very low (0.2%), responds to the concentration of added A DP, and is inhibited by malonate (75% at 2 mm), iproniazid (45% at 2 m m), beta-chloroalanine (36% at 1 mm), and aminooxyacetate (55% at 0.1 mm). With both iproniazid and aminooxyacetate, the percentage of inhib ition is the same as that observed with the latter inhibitor alone. Th ese data indicate that ALA decarboxylation by the Krebs cycle is a min or process and that it is initiated enzymically (transaminase) and not by metal-catalyzed ALA autoxidation. (C) 1994 Academic Press, Inc.