Quantitation of in vivo human folate metabolism.
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.


METHODS
Adults (n = 13) received 0.5 nmol [(14)C]pteroylmonoglutamate (100 nCi radioactivity) plus 79.5 nmol pteroylmonoglutamate 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 pteroylpolyglutamate (>98%), total body folate was 225 micromol, 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.
Lin
Yumei
Y
Departments of Nutrition and Pathology Department, University of California-Davis, One Shields Avenue,. Davis. CA 95616-8669, USA.
Dueker
Stephen R
SR
Follett
Jennifer R
JR
Fadel
James G
JG
Arjomand
Ali
A
Schneider
Philip D
PD
Miller
Joshua W
JW
Green
Ralph
R
Buchholz
Bruce A
BA
Vogel
John S
JS
Phair
Robert D
RD
Clifford
Andrew J
AJ
D000328:Adult; D002250:Carbon Radioisotopes; D004912:Erythrocytes / Q000737:chemistry; D005243:Feces / Q000737:chemistry; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005971:Glutamates / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological
D002250:Carbon Radioisotopes; D005971:Glutamates; D005492:Folic Acid; C011398:4-aminobenzoylglutamic acid