Ubiquinone biosynthesis in Leishmania major promastigotes

Promastigotes of Leishmania major contain a ubiquinone which has a side chain made up of nine isoprene subunits (UQ9). Incorporation of radioactivity from [14C] acetate and [14C] mevalonate into ubiquinone as well as the identification of hydroxymethylglutaryl coenzyme A reductase (HMG CoA reductase), and mevalonate kinase indicate that the isoprenoid portion of the molecule is synthesized by the acetate-mevalonate pathway as in mammalian cells. Incorporation of [14C] tyrosine into ubiquinone is low, but [14C] parahydroxybenzoic acid is readily incorporated. Distribution of radioactivity from [14C] acetate indicates that about 60-80% is associated with the side chain and about 20% with the ring. Label from parahydroxybenzoic acid is, however, incorporated preferentially into the ring. L. major is capable of synthesizing the aromatic ring of ubiquinone from acetate, parahydroxybenzoate being an important intermediate. In this behaviour it resembles procaryotes. Ubiquinone biosynthetic pathway in L. major thus shares characteristics with mammalian and bacterial systems.