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

• Published in: The Journal of nutrition Vol. 137; no. 12; pp. 2647 - 2652
• Main Authors: Lamers, Yvonne, Williamson, Jerry, Gilbert, Lesa R, Stacpoole, Peter W, Gregory, Jesse F. III
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.12.2007; American Society for Nutritional Sciences
• Subjects: Adult; amino acid metabolism; biochemical pathways; Biological and medical sciences; Carbon Isotopes; chemical reactions; Decarboxylation; Feeding. Feeding behavior; Female; Folic Acid - blood; Fundamental and applied biological sciences. Psychology; glycine (amino acid); Glycine - administration & dosage; Glycine - blood; Glycine - metabolism; glycine flux; human nutrition; Humans; Isotope Labeling; leucine; Leucine - administration & dosage; Leucine - metabolism; Male; men; metabolic studies; nutrition physiology; Pyridoxal Phosphate - blood; reaction kinetics; serine; Tritium; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin B 12 - blood; women; young adults; Human; Nutrition; Aminoacid; Turnover; Neurotransmitter; Female; Leucine; Glycine
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/137.12.2647

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.