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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Production of 1-Carbon Units from Glycine Is Extensive in Healthy Men and Women^1,2

³ Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, ⁴ General Clinical Research Center, ⁵ Division of Biostatistics, Department of Epidemiology and Health Policy Research, ⁶ Division of Endocrinology and Metabolism, Department of Medicine, and ⁷ Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611-0370

Glycine undergoes decarboxylation in the glycine cleavage system (GCS) to yield CO₂, NH₃, and a 1-carbon unit. CO₂ also can be generated from the 2-carbon of glycine by 10-formyltetrahydrofolate-dehydrogenase and, after glycine-to-serine conversion by serine hydroxymethyltransferase, from the tricarboxylic acid cycle. To evaluate the relative fates of glycine carbons in CO₂ generation in healthy volunteers (3 male, 3 female, aged 21–26 y), primed, constant infusions were conducted using 9.26 µmol·h^–1·kg^–1 of [1,2-¹³C]glycine and 1.87 µmol·h^–1·kg^–1 of [5,5,5-²H₃]leucine, followed by an infusion protocol using [1-¹³C]glycine as the glycine tracer. The time period between the infusion protocols was >6 mo. In vivo rates of whole-body glycine and leucine flux were nearly identical in protocols with [1,2-¹³C]glycine and [5,5,5-²H₃]leucine and with [1-¹³C]glycine and [5,5,5-²H₃]leucine tracers, which showed high reproducibility between the tracer protocols. Using the [1-¹³C]glycine tracer, breath CO₂ data showed a total rate of glycine decarboxylation of 96 ± 8 µmol·h^–1·kg^–1, which was 22 ± 3% of whole-body glycine flux. In contrast, infusion of [1,2-¹³C]glycine yielded a glycine-to-CO₂ flux of 146 ± 37 µmol·h^–1·kg^–1 (P = 0.026). By difference, this implies a rate of CO₂ formation from the glycine 2-carbon of 51 ± 40 µmol·h^–1·kg^–1, which accounts for 35% of the total CO₂ generated in glycine catabolism. These findings also indicate that 65% of the CO₂ generation from glycine occurs by decarboxylation, primarily from the GCS. Further, these results suggest that the GCS is responsible for the entry of 5,10-methylenetetrahydrofolate into 1-carbon metabolism at a very high rate (96 µmol·h^–1·kg^–1), which is 20 times the demand for methyl groups for homocysteine remethylation.

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

Manuscript received 12 December 2008. Initial review completed 14 January 2009. Revision accepted 31 January 2009.

Published online 25 February 2009.