Metabolism of malonaldehyde in vivo and in vitro

The metabolism of malonaldehyde (MA) was investigated in vivo using male Wistar rats and in vitro using rat liver mitochondria. Twelve hr after intubation with 1,3-¹⁴C] MA, 60–70%, 5–15% and 9–17% of administered radioactivity was recovered in expired CO₂, feces and urine, respectively. In rats intubated with 1,2-¹⁴C] acetate, the corresponding values were 68–82%, 1–2% and 2–3%.¹⁴CO₂ evolution was initially slower after¹⁴C-MA administration than after¹⁴C-acetate administration and more radioactivity was excreted in the feces and urine. In vitro experiments using 1,3-¹⁴C] MA showed that MA is metabolized primarily in the mitochondria via reactions involving O₂ utilization and¹⁴CO₂ production. The apparent K_m and V_max were 0.5 mM and 9.3 nmol/min/mg protein for O₂ uptake, respectively, and 2.0 mM and 2.4 nmol/min/mg protein for¹⁴CO₂ production. Addition of malonic acid to mitochondrial incubates at concentrations inhibitory to succinate dehydrogenase did not affect MA-induced O₂ uptake but enhanced¹⁴CO₂ production from¹⁴C-MA.¹⁴C-Acetate appeared to be the major accumulating metabolite in rat liver mitochondrial preparations following a 120-min incubation with¹⁴C-MA. A probable biochemical route for MA metabolism involves oxidation of MA by mitochondrial aldehyde dehydrogenase followed by decarboxylation to produce CO₂ and acetate.