CYTOCHROME-P-450 OXIDATION OF ALKANES ORIGINATING AS SCISSION PRODUCTS DURING LIPID-PEROXIDATION

Alkanes of low MW, as well as malondialdehyde, originate during lipid peroxidation. Ethane and pentane are the most prominent and are probably scission products of .omega.-3 and .omega.-6 unsaturated fatty acids, respectively. Measurement of exhaled alkanes is the most reliable procedure for determining lipid peroxidation in vivo. Alkanes appear in the breath of rats 15 min after administration of CBrCl3 i.p., and are also formed in small amounts endogenously. Alkanes exhaled from untreated rats in a closed system, in which CO2 is absorbed and O2 supplied, reached steady-state levels after different times, indicating that these volatile gases are metabolized at variable rates. Metabolism was verified by injecting alkanes into the closed system. Pentane was metabolized 5-10 times faster than ethane, and was species- and strain-dependent. Administration of drugs which inhibit or induce cytochrome P-450 indicated that a particular isoenzyme might be involved in the oxidation of small alkanes. SKF 525-A or benzoflavone did not inhibit, but tetrahydrofuran and ethanol were effective inhibitors. Inducing effects of phenobarbital, methylcholanthrene or ethanol were significant. Incubation of microsomes with NADPH and O2, either with or without Fe-ADP, to elicit lipid peroxidation confirmed the findings in vivo. Ethane and pentane were formed in similar quantities. Inhibition of alkane oxidation with CO or ethanol increased the amount of pentane 3- to 4-fold, indicating that inhibition of metabolism enhances alkane release. The ratio of unmetabolized pentane to ethane reflects the membrane ratio of .omega.-6 to .omega.-3 unsaturated acids. Different types of alkane release were observed following administration of paracetamol or CCl4 to mice, indicating differences in the peroxidative attack. CCl4 destroys cytochrome P-450 dose dependently so that it loses its capacity to oxidize pentane, whereas paracetamol does not inactivate the mono-oxygenase. Monitoring the elimination rate of injected pentane is recommended as a reliable noninvasive procedure for testing the functional state of hepatic cytochrome P-450.