VITAMIN B6 DEPENDENCE OF ONE-CARBON METABOLISM: GLYCINE CLEAVAGE ASSESSMENT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Amino acid glycine has multiple roles in human metabolism, in protein synthesis, one-carbon metabolism, purine synthesis, and component of glutathione. Through mitochondrial glycine cleavage system glycine is cleaved to CO2, NH3, and a 1C-unit in the form of 5,10-methylenetetrahydrofolate 5,10-CH2-THF. This unit from glycine is used in reactions of nucleotide synthesis, regeneration of methionine from homocysteine, and methylation of biological compounds. 1C metabolism is linked to transsulfuration pathway in which homocysteine undergoes vitamin B6 dependent catabolism leading to cysteine, whose availability governs formation of antioxidant glutathione. Nutritional or genetic conditions impairing 1C metabolism are associated with elevated plasma homocysteine concentration and increased risk of vascular disease. We will evaluate glycine metabolism using a single-labeled glycine. 6 healthy, nutritionally adequate, young adults,3 male, 3 female will undergo metabolite profiling and kinetic analysis using intravenously infused stable isotopic tracers performed after 2d of controlled, nutrient-balanced diet. We hypothesize that the rate of breath 13CO2 enrichment will be lower after infusion of [1-13C1]glycine compared to observed rate after infusion with [1,2-13C2]glycine. Results will aid assessing rate and pattern of glycine decarboxylation and metabolic products supporting investigations on relationships between glycine, vitamin B6 nutrition and disease.