Role of high-affinity folate-binding protein in the plasma distribution of tetrahydrofolate in pigs.
Stability and protein-binding properties of tetrahydrofolate (THF) in pig plasma were studied in vitro. THF in plasma was stable for more than 120 min when it existed in a bound form, whereas THF both in plasma ultrafiltrate and in plasma ultrafiltrate plus porcine albumin was degraded rapidly and disappeared soon after its addition. These results suggest that high-affinity folate-binding protein (HFBP) is related to the stability of THF. THF-protein binding kinetic analysis showed that porcine plasma had HFBP and low-affinity binding protein (albumin) for THF. Dissociation constant and maximal binding capacity of HFBP were calculated to be 0.4 and 70 nM, respectively, indicating that > 98% of endogenous plasma THF existed in bound form with HFBP. Porcine albumin was not essentially a protein that binds and protects endogenous THF from degradation. We conclude that most endogenous THF binds to HFBP and only the unbound form of THF is rapidly degraded in pig plasma. HFBP protects THF from degradation and allows THF to exist stably in pig plasma. In addition, HFBP may govern the species specificity of plasma folate distribution in pigs.
Sasaki
K
K
Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Japan.
Natsuhori
M
M
Shimoda
M
M
Saima
Y
Y
Kokue
E
E
D000818:Animals; D001667:Binding, Competitive; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000494:pharmacology; D007700:Kinetics; D011956:Receptors, Cell Surface; D013552:Swine / Q000097:blood*; D013763:Tetrahydrofolates / Q000097:blood* / Q000378:metabolism; D014462:Ultrafiltration
D001798:Blood Proteins; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D013763:Tetrahydrofolates; C030371:5,6,7,8-tetrahydrofolic acid; D005492:Folic Acid