Mitochondrial and peroxisomal metabolism of glutaryl-CoA

Using a fraction purified from liver peroxisomes, we demonstrate that products of the glutaryl-CoA oxidase reaction are glutaconyl-CoA and H2O2. No glutaconyl-CoA decarboxylation occurs with this fraction. In whole tissue homogenates, the handling of glutaryl-CoA by glutaryl-CoA dehydrogenase is inhibited when reoxidation of FADH2 is blocked. Under these conditions, glutaconyl-CoA decarboxylation, however, can still occur and 14CO2 is produced from labelled glutaryl-CoA in mole/mole ratio with H2O2. These data indicate that in the absence of its mitochondrial dehydrogenation, glutaryl-CoA is oxidized in peroxisomes to glutaconyl-CoA which is probably transferred to mitochondria where it is decarboxylated and further processed. This hypothesis allows coherent explanation for the observed organic aciduria in both glutaricaciduria types I and II.