ω‐Oxidation of Stearic Acid in the Normal, Starved and Diabetic Rat Liver

ω‐Oxidation of stearate, catalyzed by 20000 ×g supernatant fluid of rat‐liver homogenate in the presence of an NADPH‐generating system, was stimulated three‐ to seven‐fold by starvation or diabetes. The soluble fraction of liver homogenate was responsible for the stimulation. Thus, addition of 100000 ×g supernatant fluid of liver homogenate from starved rats stimulated microsomal ω1‐oxidation of stearate two‐ to three‐fold whereas addition of 100000 ×g supernatant fluid of liver homogenate from untreated rats had no effect or an inhibitory effect. Evidence was obtained to indicate that the stimulatory effect of the 100000 ×g supernatant fluid from liver of starved rats was due to the presence in this fraction of liver alcohol dehydrogenase and NAD. The role of alcohol dehydrogenase might be to protect the ω1‐hydroxylase from product inhibition by oxidation of the 18‐hydroxystearic acid formed. The effect of 100000 ×g supernatant fluid from liver of untreated rats was shown to be due to an inhibition of the ω1‐hydroxylase reaction and not of the alcohol dehydrogenase reaction. The inhibitory effect of the 100000 ×g supernatant fluid was retained after boiling for 5 min but was partially destroyed after preincubation at 37°C or after repeated freezing and thawing. The inhibition was shown to be at least not mainly due to interference with formation of stearoyl‐CoA from stearic acid. Stearoyl‐CoA was ω1‐hydroxylated by the microsomal fraction or by the 20000 ×g supernatant fluid at a rate about half that of free stearic acid. The possibility is discussed that the low extent of ω1‐oxidation of long‐chain fatty acids observed under normal conditions might be partially due to the presence of the inhibitor(s) in the soluble part of the cell and that disappearance of this inhibition under conditions of starvation and diabetes might be of physiological importance.