The Role of Leucine in Terpenoid Metabolism: Incorporation of Leucine into Sesquiterpenoids and Phytosterols by Andrographis Tissue Cultures

Abstract

The possible involvement of the amino acid leucine in the biosynthesis of isoprenoids has long been the subject of conjecture. The catabolic pathway for leucine in mammals was established in the early 1950’s, largely by the work of M.J. Coon et al. [15, 24, 36], as outlined in Scheme 1. It was subsequently shown that the same (3S)-antipode of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) (5) lies on the catabolic pathway of leucine [20, 37] (Scheme 1, a) and on the anabolic pathway from acetate to (3R)-me-valonic acid (MVA) (6) [16, 17] (Scheme 1, b). The latter is, of course, the well-established biosynthetic route to terpenoids and steroids, but the interesting question arises whether an alternative, if less important route to (3R)-MVA (6) might start from leucine, rather than acetate and proceed via HMG-CoA, incorporating the carbon skeleton of leucine intact [but for loss of C—1 in the conversion of (1) to (2)].