Document Detail


Pneumocystis carinii f. sp. carinii synthesizes de novo four homologs of ubiquinone.
MedLine Citation:
PMID:  12095106     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
D Sul; E S Kaneshiro
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of eukaryotic microbiology     Volume:  48     ISSN:  1066-5234     ISO Abbreviation:  J. Eukaryot. Microbiol.     Publication Date:    2001 Mar-Apr
Date Detail:
Created Date:  2002-07-03     Completed Date:  2002-07-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9306405     Medline TA:  J Eukaryot Microbiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  182-7     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, University of Cincinnati, Ohio 45221, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Coenzymes
Female
Lovastatin / pharmacology
Lung / metabolism,  microbiology
Mevalonic Acid / metabolism
Parabens
Phosphoenolpyruvate / metabolism
Pneumocystis / isolation & purification,  metabolism*
Pneumonia, Pneumocystis / microbiology
Rats
Rats, Inbred Lew
Shikimic Acid / metabolism
Tyrosine / metabolism
Ubiquinone / analogs & derivatives*,  biosynthesis*
Grant Support
ID/Acronym/Agency:
R01 AI28757/AI/NIAID NIH HHS; R01 AI29316/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Coenzymes; 0/Parabens; 1339-63-5/Ubiquinone; 138-59-0/Shikimic Acid; 150-97-0/Mevalonic Acid; 2394-68-5/ubiquinone 8; 303-95-7/ubiquinone 7; 303-97-9/ubiquinone 9; 303-98-0/coenzyme Q10; 55520-40-6/Tyrosine; 73-89-2/Phosphoenolpyruvate; 75330-75-5/Lovastatin; 99-96-7/4-hydroxybenzoic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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