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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Glycine Turnover and Decarboxylation Rate Quantified in Healthy Men and Women Using Primed, Constant Infusions of [1,2-¹³C₂]Glycine and [²H₃]Leucine^1,2

³ Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences; ⁴ Division of Endocrinology and Metabolism, Department of Medicine; and ⁵ Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611-0370

^* To whom correspondence should be addressed. E-mail: jfgy{at}ufl.edu.

Glycine plays several roles in human metabolism, e.g. as a 1-carbon donor, in purine synthesis, and as a component of glutathione. Glycine is decarboxylated via the glycine cleavage system (GCS) that yields concurrent generation of a 1-carbon unit as 5,10-methylenetetrahydrofolate (methyleneTHF). Serine hydroxymethyltransferase (SHMT) catalyzes the interconversion of glycine and serine, another 1-carbon donor. The quantitative role of glycine in human 1-carbon metabolism has received little attention. The aim of this protocol was to quantify whole body glycine flux, glycine to serine flux, and rate of glycine cleavage in humans. A primed, constant infusion with 9.26 µmol·kg^–1·h^–1 [1,2-¹³C₂]glycine and 1.87 µmol·kg^–1·h^–1 [²H₃]leucine was used to quantify the kinetic behavior of glycine in young, healthy volunteers (n = 5) in a fed state. The isotopic enrichment of infused tracers and metabolic products in plasma, as well as breath ¹³CO₂ enrichment, were determined for use in kinetic analysis. Serine synthesis by direct conversion from glycine via SHMT occurred at 193 ± 28 µmol·kg^–1·h^–1 (mean ± SEM), which comprised 41% of the 463 ± 55 µmol·kg^–1·h^–1 total glycine flux. Nearly one-half (46%) of the glycine-to-serine conversion occurred using GCS-derived methyleneTHF 1-carbon units. Based on breath ¹³CO₂ measurement, glycine decarboxylation (190 ± 41 µmol·kg^–1·h^–1) accounted for 39 ± 6% of whole body glycine flux. This study is the first to our knowledge to quantify human glycine cleavage and glycine-to-serine SHMT kinetics. GCS is responsible for a substantial proportion of whole body glycine flux and constitutes a major route for the generation of 1-carbon units.