title: Oral antibodies to human intestinal alkaline phosphatase reduce dietary phytate phosphate bioavailability in the presence of dietary 1α-hydroxycholecalciferol.
abstract: While it is well established that active vitamin D treatment increases dietary phytate phosphate utilization, the mechanism by which intestinal alkaline phosphatase (IAP) participates in phytate phosphate use is less clear. The ability of human IAP (hIAP) oral antibodies to prevent dietary phytate phosphate utilization in the presence of 1α-hydroxycholecalciferol (1α-(OH) D3) in a chick model was investigated. hIAP specific chicken immunoglobulin Y (IgY) antibodies were generated by inoculating laying hens with 17 synthetic peptides derived from the human IAP amino acid sequence and harvesting egg yolk. Western blot analysis showed all antibodies recognized hIAP and 6 of the 8 antibodies selected showed modest inhibition of hIAP activity in vitro (6 to 33% inhibition). In chicks where dietary phosphate was primarily in the form of phytate, 4 selected hIAP antibodies inhibited 1α-(OH) D3-induced increases in blood phosphate, one of which, generated against selected peptide (MFPMGTPD), was as effective as sevelamer hydrochloride in preventing the 1α-(OH) D3-induced increase in blood phosphate, but ineffective in preventing an increase in body weight gain and bone ash induced by 1α-(OH) D3. These studies demonstrated that orally-delivered antibodies to IAP limit dietary phytate-phosphate utilization in chicks treated with 1α-(OH) D3, and implicate IAP as an important host enzyme in increasing phytate phosphate bioavailability in 1α-(OH) D3 fed chicks.
authors.affiliation: Animal Sciences Department, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bobeck
authors.affiliation: Animal Sciences Department, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Hellestad
authors.affiliation: Cytochroma Inc., Markham, Ontario, Canada.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Helvig
authors.affiliation: Cytochroma Inc., Markham, Ontario, Canada Department of Biomedical and Molecular Sciences & Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
authors.forename: P Martin
authors.initials: PM
authors.lastname: Petkovich
authors.affiliation: Animal Sciences Department, University of Wisconsin-Madison, Madison, Wisconsin, USA mcook@wisc.edu.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cook
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D001682:Biological Availability; D002645:Chickens / Q000378:metabolism*; D004032:Diet / Q000662:veterinary*; D058851:GPI-Linked Proteins / Q000378:metabolism; D006887:Hydroxycholecalciferols / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000097:blood / Q000378:metabolism*; D010833:Phytic Acid / Q000378:metabolism
chemical_list: D000906:Antibodies; D058851:GPI-Linked Proteins; D006887:Hydroxycholecalciferols; D010710:Phosphates; D010833:Phytic Acid; C063088:ALPI protein, human; D000469:Alkaline Phosphatase; C008088:alfacalcidol
keywords: 1α-hydroxycholecalciferol; egg antibody; intestinal alkaline phosphatase; phosphate bioavailability; sevelamer hydrochloride