Recurrent Mutations in P- and T-Proteins of the Glycine Cleavage Complex and a Novel T-Protein Mutation (N145I): A Strategy for the Molecular Investigation of Patients with Nonketotic Hyperglycinemia (NKH)

2001 ◽  
Vol 72 (4) ◽  
pp. 322-325 ◽  
Author(s):  
Jennifer R. Toone ◽  
Derek A. Applegarth ◽  
Marion B. Coulter-Mackie ◽  
Erick R. James
Keyword(s):  
Protein Mutation ◽  
Recurrent Mutations ◽  
Molecular Investigation ◽  
Cleavage Complex ◽  
Glycine Cleavage ◽  
Nonketotic Hyperglycinemia

Efficacy of Tryptophan for the Treatment of Nonketotic Hyperglycinemia: A New Therapeutic Approach for Modulating the N-Methyl-D-aspartate Receptor

PEDIATRICS ◽  
1995 ◽  
Vol 95 (1) ◽  
pp. 142-146
Author(s):  
Satoshi Matsuo ◽  
Fumio Inoue ◽  
Yoshihiro Takeuchi ◽  
Hiroshi Yoshioka ◽  
Akihiko Kinugasa ◽  
...  
Keyword(s):  
Excitatory Amino Acid ◽  
Muscular Hypotonia ◽  
Inherited Disease ◽  
Excitatory Amino Acid Receptors ◽  
Amino Acid Receptors ◽  
Aspartate Receptor ◽  
Cleavage Enzyme ◽  
Glycine Cleavage ◽  
Glycine Level ◽  
Nonketotic Hyperglycinemia

Nonketotic hyperglycinemia (NKH) is a rare inherited disease caused by a defect of the glycine cleavage enzyme.1 Especially in the neonatal type, neurological symptoms such as muscular hypotonia, seizures, respiratory distress, and lethargy develop rapidly, and the prognosis is unfavorable.1 Elevation of glycine in the cerebrospinal fluid (CSF) is thought to be responsible for these symptoms. However, management is quite difficult, because it is not well understood how elevation of glycine causes these symptoms. Lowering of the glycine level in CSF with sodium benzoate is not enough to avoid severe psychomotor and mental retardation. The N-methyl-D-aspartate (NMDA) receptor, which is one of the excitatory amino acid receptors, has a glycine binding site.2

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.

Nonketotic hyperglycinemia: Analyses of glycine cleavage system in typical and atypical cases

1987 ◽  
Vol 110 (6) ◽  
pp. 873-877 ◽  
Author(s):  
Kiyoshi Hayasaka ◽  
Keiya Tada ◽  
Noboru Fuekl ◽  
Yasuhide Nakamura ◽  
William L. Nyhan ◽  
...  
Keyword(s):  
Glycine Cleavage System ◽  
Glycine Cleavage ◽  
Nonketotic Hyperglycinemia

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

Feasibility of prenatal diagnosis of nonketotic hyperglycinemia: Existence of the glycine cleavage system in placenta

1987 ◽  
Vol 110 (1) ◽  
pp. 124-126 ◽  
Author(s):  
Kiyoshi Hayasaka ◽  
Keiya Tada ◽  
Noboru Fueki ◽  
Iku Takahashi ◽  
Akira Igarashi ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Glycine Cleavage System ◽  
Glycine Cleavage ◽  
Nonketotic Hyperglycinemia
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