title: Production of 1-carbon units from glycine is extensive in healthy men and women.
abstract: Glycine undergoes decarboxylation in the glycine cleavage system (GCS) to yield CO(2), NH(3), and a 1-carbon unit. CO(2) 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 CO(2) generation in healthy volunteers (3 male, 3 female, aged 21-26 y), primed, constant infusions were conducted using 9.26 micromol x h(-1) x kg(-1) of [1,2-(13)C]glycine and 1.87 micromol x h(-1) x kg(-1) of [5,5,5-(2)H(3)]leucine, followed by an infusion protocol using [1-(13)C]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-(13)C]glycine and [5,5,5-(2)H(3)]leucine and with [1-(13)C]glycine and [5,5,5-(2)H(3)]leucine tracers, which showed high reproducibility between the tracer protocols. Using the [1-(13)C]glycine tracer, breath CO(2) data showed a total rate of glycine decarboxylation of 96 +/- 8 micromol x h(-1) x kg(-1), which was 22 +/- 3% of whole-body glycine flux. In contrast, infusion of [1,2-(13)C]glycine yielded a glycine-to-CO(2) flux of 146 +/- 37 micromol x h(-1) x kg(-1) (P = 0.026). By difference, this implies a rate of CO(2) formation from the glycine 2-carbon of 51 +/- 40 micromol x h(-1) x kg(-1), which accounts for approximately 35% of the total CO(2) generated in glycine catabolism. These findings also indicate that approximately 65% of the CO(2) 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 ( approximately 96 micromol x h(-1) x kg(-1)), which is approximately 20 times the demand for methyl groups for homocysteine remethylation.
authors.affiliation: Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, College of Medicine, University of Florida, Gainesville, FL 32611-0370, USA.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lamers
authors.forename: Jerry
authors.initials: J
authors.lastname: Williamson
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Theriaque
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: Lesa R
authors.initials: LR
authors.lastname: Gilbert
authors.forename: Christine
authors.initials: C
authors.lastname: Keeling
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stacpoole
authors.forename: Jesse F
authors.initials: JF
authors.lastname: Gregory
mesh_terms: D000328:Adult; D001835:Body Weight; D002244:Carbon / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D005260:Female; D005998:Glycine / Q000378:metabolism; D006262:Health; D006801:Humans; D008297:Male
chemical_list: D002245:Carbon Dioxide; D002244:Carbon; D005998:Glycine