Clinical effects of serine medication in non-ketotic hyperglycinaemia due to deficiency of p-protein of the glycine cleavage complex

1988 ◽  
Vol 11 (S2) ◽  
pp. 218-220 ◽  
Author(s):  
F. A. Wijburg ◽  
C. J. de Groot ◽  
R. B. H. Schutgens ◽  
P. G. Barth ◽  
K. Tada
Keyword(s):  
Clinical Effects ◽  
P Protein ◽  
Cleavage Complex ◽  
Glycine Cleavage

scholarly journals Folate metabolic pathways in Leishmania

2011 ◽  
Vol 51 ◽  
pp. 63-80 ◽  
Author(s):  
Tim J. Vickers ◽  
Stephen M. Beverley
Keyword(s):  
Protective Immunity ◽  
Mitochondrial Protein ◽  
Purine Salvage ◽  
Genetic Studies ◽  
Ts Mutant ◽  
Metabolic Reactions ◽  
Cleavage Complex ◽  
Glycine Cleavage ◽  
Antifolate Drugs ◽  
Genus Leishmania

Trypanosomatid parasitic protozoans of the genus Leishmania are autotrophic for both folate and unconjugated pteridines. Leishmania salvage these metabolites from their mammalian hosts and insect vectors through multiple transporters. Within the parasite, folates are reduced by a bifunctional DHFR (dihydrofolate reductase)-TS (thymidylate synthase) and by a novel PTR1 (pteridine reductase 1), which reduces both folates and unconjugated pteridines. PTR1 can act as a metabolic bypass of DHFR inhibition, reducing the effectiveness of existing antifolate drugs. Leishmania possess a reduced set of folate-dependent metabolic reactions and can salvage many of the key products of folate metabolism from their hosts. For example, they lack purine synthesis, which normally requires 10-formyltetrahydrofolate, and instead rely on a network of purine salvage enzymes. Leishmania elaborate at least three pathways for the synthesis of the key metabolite 5,10-methylene-tetrahydrofolate, required for the synthesis of thymidylate, and for 10-formyltetrahydrofolate, whose presumptive function is for methionyl-tRNAMet formylation required for mitochondrial protein synthesis. Genetic studies have shown that the synthesis of methionine using 5-methyltetrahydrofolate is dispensable, as is the activity of the glycine cleavage complex, probably due to redundancy with serine hydroxymethyltransferase. Although not always essential, the loss of several folate metabolic enzymes results in attenuation or loss of virulence in animal models, and a null DHFR-TS mutant has been used to induce protective immunity. The folate metabolic pathway provides numerous opportunities for targeted chemotherapy, with strong potential for ‘repurposing' of compounds developed originally for treatment of human cancers or other infectious agents.

scholarly journals Crystal structure of P-protein of the glycine cleavage system

2005 ◽  
Vol 61 (a1) ◽  
pp. c189-c190
Author(s):  
T. Nakai ◽  
N. Nakagawa ◽  
N. Maoka ◽  
R. Masui ◽  
S. Kuramitsu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Glycine Cleavage System ◽  
P Protein ◽  
Glycine Cleavage

scholarly journals The Role of the Mitochondrial Glycine Cleavage Complex in the Metabolism and Virulence of the Protozoan ParasiteLeishmania major

2007 ◽  
Vol 283 (1) ◽  
pp. 155-165 ◽  
Author(s):  
David A. Scott ◽  
Suzanne M. Hickerson ◽  
Tim J. Vickers ◽  
Stephen M. Beverley
Keyword(s):  
Cleavage Complex ◽  
Glycine Cleavage
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