Pneumocystis carinii f. sp. carinii synthesizes de novo four homologs of ubiquinone

Dong Geun Sul, E. S. Kaneshiro

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Ubiquinone, coenzyme Q, plays a pivotal role in electron transport and is a target for chemotherapy against a number of eukaryotic infectious agents, including Pneumocystis carinii. Coenzyme Q10 was previously identified as the major ubiquinone homolog in P. carinii isolated and purified from rat lungs; CoQ9 was also present. In contrast, CoQ9 and CoQ8 (but not CoQ10) were detected in the lungs of uninfected rat controls. These observations suggested that the pathogen synthesizes CoQ10, and perhaps CoQ9 as well. In the present study, CoQ biosynthesis in P. carinii was examined in greater detail. Radiolabeled mevalonate, a precursor of the CoQ polyprenyl chain, was incorporated in vitro into P. carinii ubiquinones. Incorporation of radiolabeled mevalonate into P. carinii CoQ was not enhanced by treating cells with lovastatin, suggesting that the cells did not transport the drug, or that a lovastatin-insensitive pathway for de novo synthesis of isoprenoids may also function in this organism. Radiolabeled precursors of the ring moiety, including shikimic acid, p-hydroxybenzoic acid, and tyrosine were also incorporated into P. carinii CoQ. Unexpectedly, it was found that not only CoQ9 and CoQ10, but also CoQ7, and CoQ8, were metabolically radiolabeled by all the precursors tested, indicating that the organism synthesizes CoQ7, CoQ8, CoQ9, and CoQ10. Metabolic radiolabeling of ubiquinones in rat lung controls was not detected in experiments using either radioactive mevalonate or p-hydroxybenzoate. Thus the incorporations measured using purified P. carinii preparations were due to the enzymes of the organism.

Original languageEnglish
Pages (from-to)182-187
Number of pages6
JournalJournal of Eukaryotic Microbiology
Volume48
Issue number2
Publication statusPublished - 2001 Jul 31
Externally publishedYes

Fingerprint

coenzyme Q10
Pneumocystis carinii
Ubiquinone
ubiquinones
Mevalonic Acid
lovastatin
Lovastatin
lungs
Lung
rats
organisms
Shikimic Acid
shikimic acid
Hydroxybenzoates
radiolabeling
4-hydroxybenzoic acid
pathogens
isoprenoids
Terpenes
Electron Transport

Keywords

  • AIDS
  • High performance liquid chromatography
  • Lovastatin
  • Mevalonic acid
  • P-hydroxybenzoic acid
  • Phosphoenolpyruvate
  • Shikimic acid
  • Tyrosine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Agricultural and Biological Sciences (miscellaneous)
  • Applied Microbiology and Biotechnology
  • Microbiology

Cite this

Pneumocystis carinii f. sp. carinii synthesizes de novo four homologs of ubiquinone. / Sul, Dong Geun; Kaneshiro, E. S.

In: Journal of Eukaryotic Microbiology, Vol. 48, No. 2, 31.07.2001, p. 182-187.

Research output: Contribution to journalArticle

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abstract = "Ubiquinone, coenzyme Q, plays a pivotal role in electron transport and is a target for chemotherapy against a number of eukaryotic infectious agents, including Pneumocystis carinii. Coenzyme Q10 was previously identified as the major ubiquinone homolog in P. carinii isolated and purified from rat lungs; CoQ9 was also present. In contrast, CoQ9 and CoQ8 (but not CoQ10) were detected in the lungs of uninfected rat controls. These observations suggested that the pathogen synthesizes CoQ10, and perhaps CoQ9 as well. In the present study, CoQ biosynthesis in P. carinii was examined in greater detail. Radiolabeled mevalonate, a precursor of the CoQ polyprenyl chain, was incorporated in vitro into P. carinii ubiquinones. Incorporation of radiolabeled mevalonate into P. carinii CoQ was not enhanced by treating cells with lovastatin, suggesting that the cells did not transport the drug, or that a lovastatin-insensitive pathway for de novo synthesis of isoprenoids may also function in this organism. Radiolabeled precursors of the ring moiety, including shikimic acid, p-hydroxybenzoic acid, and tyrosine were also incorporated into P. carinii CoQ. Unexpectedly, it was found that not only CoQ9 and CoQ10, but also CoQ7, and CoQ8, were metabolically radiolabeled by all the precursors tested, indicating that the organism synthesizes CoQ7, CoQ8, CoQ9, and CoQ10. Metabolic radiolabeling of ubiquinones in rat lung controls was not detected in experiments using either radioactive mevalonate or p-hydroxybenzoate. Thus the incorporations measured using purified P. carinii preparations were due to the enzymes of the organism.",
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