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, hereditary tyrosinemia, and saturnism, was previously shown to yield reactive oxygen species upon metal-catalyzed aerobic oxidation and to cause the in vivo and in vitro impairment of rat liver mitochondrial functions. We have studied the uptake and catabolism of [5-14C]ALA to CO2 by isolated rat liver mitochondria (RLM) with the aim of determining whether possible ALA-driven oxidative injury to mitochondria can also occur into the matrix. Using silicone oil centrifugation of [5-14C]ALA-treated RLM, ALA was found to partition evenly into the intra- and extramatrix space of the mitochondrial preparations. The yield of evolved 14CO2 is very low (0.2%), responds to the concentration of added ADP, and is inhibited by malonate (75% at 2 mM), iproniazid (45% at 2 mM), beta-chloroalanine (36% at 1 mM), and aminooxyacetate (55% at 0.1 mM). With both iproniazid and aminooxyacetate, the percentage of inhibition is the same as that observed with the latter inhibitor alone. These data indicate that ALA decarboxylation by the Krebs cycle is a minor process and that it is initiated enzymically (transaminase) and not by metal-catalyzed ALA autoxidation.
Medeiros
M H
MH
Instituto de Química, Universidade de São Paulo, Brazil.
Di Mascio
P
P
Gründel
S
S
Soboll
S
S
Sies
H
H
Bechara
E J
EJ
D000622:Aminolevulinic Acid / Q000378:metabolism*; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002451:Cell Compartmentation; D007490:Iproniazid / Q000494:pharmacology; D008314:Malonates / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017382:Reactive Oxygen Species; D000637:Transaminases / Q000037:antagonists & inhibitors; D014631:Valerates / Q000378:metabolism; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000494:pharmacology
D008314:Malonates; D008996:Monoamine Oxidase Inhibitors; D000644:Quaternary Ammonium Compounds; D017382:Reactive Oxygen Species; D014631:Valerates; D015091:beta-Alanine; D002245:Carbon Dioxide; D000625:Aminooxyacetic Acid; C006977:3-chloroalanine; C007509:4,5-dioxovaleric acid; D000622:Aminolevulinic Acid; C030290:malonic acid; D007490:Iproniazid; D000637:Transaminases