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

Glycine undergoes decarboxylation in the glycine cleavage system (GCS) to yield CO2, NH3, and a 1-carbon unit. CO2 also car) 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 mu mol.h(-1).kg(-1) of [1,2-C-13]glycine and 1.87 mu mol.h(-1).kg(-1) of [5,5,5-H-2(3)]leucine, followed by an infusion protocol using [1-C-13]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-C-13]glycine and [5,5,5-H-2(3)]leucine and with [1-C-13]glycine and [5,5, 5-H-2(3)]leucine tracers, which showed high reproducibility between the tracer protocols. Using the [1-C-13]glycine tracer, breath CO2 data showed a total rate of glycine decarboxylation of 96 +/- 8 mu mol.h(-1).kg(-1), which was 22 +/- 3% of whole-body glycine flux. In contrast, infusion of [1,2-C-13]glycine yielded a glycine-to-CO2 flux of 146 +/- 37 mu mol.h(-1).kg(-1) (P=0.026). By difference, this implies a rate of CO2 formation from the glycine 2-carbon of 51 +/- 40 mu mol.h(-1).kg(-1), which accounts for similar to 35% of the total CO2 generated in glycine catabolism, These findings also indicate that similar to 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-methylenetelrahydrofolate into 1-carbon metabolism at a very high rate (similar to 96 mu mol.h(-1).kg(-1)), which is similar to 20 times the demand for methyl groups for homocysteine remethylation. J. Nutr. 139: 666-671, 2009.