Nonenzymatic reduction of prostaglandin H by lipoic acid.

Lipoic acid has recently been found to stimulate prostaglandin biosynthesis by sheep vesicular gland microsomes (Marnett, L. J., and Wilcox, C. L. (1977). Biochim. Biophys. Acta 487, 222). The increase in oxygenated products is predominantly in the formation of prostaglandin F and its structure has been verified by gas chromatography-mass spectrometry. Endoperoxide trapping experiments employing reduced glutathione show that the conversion of prostaglandin H to prostaglandin F is slow in lipoate containing incubation mixtures. Therefore, the net effect of the addition of lipoic acid to vesicular gland microsomes is the stimulation of prostaglandin endoperoxide biosynthesis. Further experiments reveal that the reduction of prostaglandin H to prostaglandin F by lipoate is nonenzymatic and occurs after the termination of biosynthesis in the work-up mixture. The reduction takes place preferentially in the organic phase of a Folch extract (chloroform-methanol-2% formic acid 8:4:3). Authentic prostaglandin H2 is reduced by lipoic acid to prostaglandin F 2alpha in high yield under these conditions.