COMPOSITION OF PNEUMOCYSTIS-CARINII NEUTRAL LIPIDS AND IDENTIFICATIONOF COENZYME Q(10) AS THE MAJOR UBIQUINONE HOMOLOG

The lipids of purified preparations of Pneumocystis carinii carinii fr eshly isolated from infected rats were analyzed and compared with thos e of whole lungs from normal and methylprednisolone-immunosuppressed u ninfected rats. In this study, the neutral lipid fraction was examined in detail; the relative concentrations of individual classes making u p this fraction were quantified. Of particular interest was the nature of the organism's ubiquinone (coenzyme Q, CoQ) fraction because atova quone, a hydroxynaphthoquinone (566C80) analog of ubiquinone, is effic acious in the treatment of P. carinii pneumonia. The ubiquinone concen tration in both P. carinii and lung tissues was relatively low compare d to that present in rat heart and liver tissues. Two homologs were id entified in the organism: CoQ(10) was the predominant homolog with les ser amounts of CoQ(9) present. In contrast, the lungs of normal and im munosuppressed uninfected rats had CoQ(9) and lesser amounts of CoQ(8) , but no detectable CoQ(10). Furthermore, radiolabeled mevalonic acid was incorporated in vitro into the ubiquinone fraction of P. carinii i ndicating that the organism has the de novo branch of the isoprenoid b iosynthetic pathway leading to polyprenyl formation. Hence, it was con cluded that CoQ(10) (if not both CoQ(10) and CoQ(9)) in P. carinii was not scavenged from the host but was synthesized by the organism. Alth ough lung tissues contained substantial free fatty acids, the organism was enriched in these lipids. The high concentration of free fatty ac ids and relatively low level of triglycerides in P. carinii suggest th at fatty acids may represent major carbon sources for ATP production b y the organism.