Regulation of secondary metabolism in higher plants. Effect of alkaloids on a cytochrome p-450 dependent monooxygenase

An end-product indole alkaloid, catharanthine, inhibits a membranebound cytochrome P-450 dependent monooxygenase of the higher plant, Vinca rosea. Kinetic analysis revealed the alkaloid to be a reversible, linear, non-competitive inhibitor (Ki=l mM)with resp.ect to its substrates, geraniol and NADPH. Comparable inhibition of the solubilised monooxygenase by catharanthine tends to exclude a mechanism based upon disruption of membrane organization. On the basis of its inhibition of solubilized hydroxylase in the presence and absence of sodium cholate, it is also unlikely that catharanthine competes for putative phospholipid binding site(s). Two additional end-product alkaloids, vinblastine and vindoline were less inhibitory. Since the hydroxylase catalyzes one of the first committed steps in the biosynthesis of indole alkaloids, these observations suggest feedback control of the pathway by catharanthine.