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ORIGINAL RESEARCH COMMUNICATION |
1 From the Departments of Nutrition (YL, SRD, JRF, AA, and AJC) and Animal Science (JGF), University of California, Davis; the Cancer Center (PDS) and Pathology Department (JWM and RG), University of California Davis Medical Center, Sacramento; the Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA (BAB and JSV); and Integrative BioInformatics Inc, Rockville, MD (RDP)
Background: A quantitative understanding of human folate metabolism is needed.
Objective: The objective was to quantify and interpret human folate metabolism as it might occur in vivo.
Design: Adults (n = 13) received 0.5 nmol [14C]pteroylmonoglutamate (100 nCi radioactivity) plus 79.5 nmol pteroylmonoglutamate in water orally. 14C was measured in plasma, erythrocytes, urine, and feces for 
40 d. Kinetic modeling was used to analyze and interpret the data.
Results: According to the data, the population was healthy and had a mean dietary folate intake of 1046 nmol/d, and the apparent dose absorption of 14C was 79%. The model predictions showed that only 0.25% of plasma folate was destined for marrow, mean bile folate flux was 5351 nmol/d, and the digestibility of the mix (1046 + 5351 nmol/d) was 92%. About 33% of visceral pteroylmonoglutamate was converted to the polyglutamate form, most of the body folate was visceral (>99%), most of the visceral folate was pteroylpolyglutamate (>98%), total body folate was 225 µmol, and pteroylpolyglutamate synthesis, recycling, and catabolism were 1985, 1429, and 556 nmol/d, respectively. Mean residence times were 0.525 d as visceral pteroylmonoglutamate, 119 d as visceral pteroylpolyglutamate, 0.0086 d as plasma folate, and 0.1 d as gastrointestinal folate.
Conclusions: Across subjects, folate absorption, bile folate flux, and body folate stores were larger than prior estimates. Marrow folate uptake and pteroylpolyglutamate synthesis, recycling, and catabolism are saturable processes. Visceral pteroylpolyglutamate was an immediate precursor of plasma p-aminobenzoylglutamate. The model is a working hypothesis with derived features that are explicitly model-dependent. It successfully quantitated folate metabolism, encouraging further rigorous testing.
Key Words: Folate • metabolism • 14C • accelerator mass spectrometry • kinetic model
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