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Unformatted text preview: Quantitation of in vivo human folate metabolism 13 Yumei Lin, Stephen R Dueker, Jennifer R Follett, James G Fadel, Ali Arjomand, Philip D Schneider, Joshua W Miller, Ralph Green, Bruce A Buchholz, John S Vogel, Robert D Phair, and Andrew J Clifford ABSTRACT Background: A quantitative understanding of human folate metab- olism 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 [ 14 C]pteroylmonoglu- tamate (100 nCi radioactivity) plus 79.5 nmol pteroylmonogluta- mate in water orally. 14 C 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 14 C 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 pteroylpoly- glutamate ( 98%), total body folate was 225 mol, and pteroyl- polyglutamate 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 pteroyl- polyglutamate, 0.0086 d as plasma folate, and 0.1 d as gastrointes- tinal 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 me- tabolism, encouraging further rigorous testing. Am J Clin Nutr 2004;80:680 91. KEY WORDS Folate, metabolism, 14 C, accelerator mass spectrometry, kinetic model INTRODUCTION A steady supply of dietary folate is needed to maintain bio- chemical reactions that include purine and pyrimidine synthesis and the metabolism of homocysteine to methionine. The com- plex interactions of genetic and dietary factors can cause irreg- ularities in the supply and metabolism of folate and lead to seri- ous health problems. Although folate has been studied extensively (15), the quan- titative aspects of folate metabolism in humans are still of con- siderable interest. Once radiolabeled folate becomes available, key aspects of folate metabolism can be quantified. Prior esti- mates indicate that 95% of an oral dose of [ 3 H]pteroylmono- glutamate is absorbed, and that the radiolabel peaks in serum 12 h after the dose (6). Furthermore, during the first 12 h after theh after the dose (6)....
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