Linked Life Data

17981801

Source:http://linkedlifedata.com/resource/pubmed/id/17981801

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-31
pubmed:abstractText
For the human pathogen Leishmania major, a key metabolic function is the synthesis of thymidylate, which requires 5,10-methylenetetrahydrofolate (5,10-CH(2)-THF). 5,10-CH(2)-THF can be synthesized from glycine by the mitochondrial glycine cleavage complex (GCC). Bioinformatic analysis revealed the four subunits of the GCC in the L. major genome, and the role of the GCC in parasite metabolism and virulence was assessed through studies of the P subunit (glycine decarboxylase (GCVP)). First, a tagged GCVP protein was expressed and localized to the parasite mitochondrion. Second, a gcvP(-) mutant was generated and shown to lack significant GCC activity using an indirect in vivo assay after incorporation of label from [2-(14)C]glycine into DNA. The gcvP(-) mutant grew poorly in the presence of excess glycine or minimal serine; these studies also established that L. major promastigotes require serine for optimal growth. Although gcvP(-) promastigotes and amastigotes showed normal virulence in macrophage infections in vitro, both forms of the parasite showed substantially delayed replication and lesion pathology in infections of both genetically susceptible or resistant mice. These data suggest that, as the physiology of the infection site changes during the course of infection, so do the metabolic constraints on parasite replication. This conclusion has great significance to the interpretation of metabolic requirements for virulence. Last, these studies call attention in trypanosomatid protozoa to the key metabolic intermediate 5,10-CH(2)-THF, situated at the junction of serine, glycine, and thymidylate metabolism. Notably, genome-based predictions suggest the related parasite Trypanosoma brucei is totally dependent on the GCC for 5,10-CH(2)-THF synthesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
155-65
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:17981801-Animals, pubmed-meshheading:17981801-Genome, Protozoan, pubmed-meshheading:17981801-Glycine Dehydrogenase (Decarboxylating), pubmed-meshheading:17981801-Green Fluorescent Proteins, pubmed-meshheading:17981801-Leishmania major, pubmed-meshheading:17981801-Leishmaniasis, Cutaneous, pubmed-meshheading:17981801-Macrophages, pubmed-meshheading:17981801-Methotrexate, pubmed-meshheading:17981801-Mice, pubmed-meshheading:17981801-Mice, Inbred BALB C, pubmed-meshheading:17981801-Microscopy, Fluorescence, pubmed-meshheading:17981801-Mitochondria, pubmed-meshheading:17981801-Models, Genetic, pubmed-meshheading:17981801-Mutation, pubmed-meshheading:17981801-Phenotype, pubmed-meshheading:17981801-Protozoan Proteins, pubmed-meshheading:17981801-Recombinant Fusion Proteins, pubmed-meshheading:17981801-Trypanosoma brucei brucei, pubmed-meshheading:17981801-Virulence
pubmed:year
2008
pubmed:articleTitle
The role of the mitochondrial glycine cleavage complex in the metabolism and virulence of the protozoan parasite Leishmania major.
pubmed:affiliation
Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural