Cytochrome P-450 and oxidative metabolism in invertebrates.

expression or are other molecular mechanisms operative? Unfortunately, we do not have precise answers to these questions at present owing to lack of information on the 5‘ upstream regulatory elements of genomic cytochrome P450 IVAl. It is interesting to draw attention to the mechanism proposed by Elcombe and his colleagues, whereby lipid biotransformation is again involved [ 151, similar to the possible regulation of constitutive cytochrorne P450 IVAl gene expression described above. In this particular mechanism, the inducer is taken up by the hepatocyte and initially directly inhibits the mitochondrial B-oxidation enzyme specific for medium-chain fatty acids, and/or the carnitine acyl transferase responsible for the transport of mediumchain acylcarnitines across the mitochondrial membrane. Alternatively, it has been postulated that the CoA derivatives o f oxyisobutyric acid inducers per se or CoA sequestration by fatty acids are responsible for the initial inhibition of fatty acid oxidation. Accordingly, the cellular levels of mediumchain fatty acids accumulate (either per se or as their CoA esters), and it is postulated 1151 that these lipids induce microsomal cytochrome P450 lVAl to maintain lipid homoeostasis, as this haemoprotein will efficiently oxidize these fatty acids [ 12, 211; this is. therefore, another possible example of the well-documented phenomenon of substrate regulation of gene expression. This substrate overload perturbation of lipid metabolism may then be the common factor that readily explains the diversity of chemical structures and physiological conditions that have been reported to alter cytochrome P450 IVA 1 gene expression.