Tetrahydrobiopterin in intestinal lumen: its absorption and secretion in the small intestine and the elimination in the large intestine.
In treating hereditary deficiency of tetrahydrobiopterin (BH(4)), supplementation with BH(4) might be the ultimate choice of therapy. Oral administration of BH(4) has been believed to be inefficient owing to poor absorption of BH(4) in the intestine. In this study, we found a considerable amount of BH(4) as well as its oxidized pterins in the ingredients of intestinal lumen of mice when they were served food that did not contain significant amounts of biopterin. Ligation of the biliary duct led to significant decrease in luminal biopterin. Supplementation of BH(4) either by intraperitoneal administration of sepiapterin or of 6RBH(4) ((6R)-L-erythro-5,6,7,8-tetrahydrobiopterin) increased the BH(4) content in the intestinal lumen with a slight delay after the rise of blood BH(4). In these mice, biopterin appeared in the large intestine, caecum and colon, 2 h after the administration. The appearance of BH(4) in the large intestine was accompanied by a large amount of pterin (2-amino-4-hydroxypteridine). The amounts of biopterin + pterin that appeared in the large intestine after intraperitoneal administration of BH(4) were not greater than those found after oral administration at the same dose. When the mice were treated with a large dose of antibiotics prior to the BH(4) administration, the amount of biopterin increased in the caecum but the amount of pterin decreased greatly. These results suggested that a large proportion of BH(4) administered moved to the large intestine, where most biopterin was decomposed presumably by enteric bacteria. Nonetheless, most of the orally administered biopterin was taken up by the small intestine and the amount of biopterin reaching the large intestine was almost the same as that which appeared after direct injection of 6RBH(4) into the peritoneal cavity.
Sawabe
K
K
Department of Biosciences, Teikyo University of Science and Technology, Uenohara, Yamanashi, Japan.
Saeki
Y
Y
Ohashi
A
A
Mamada
K
K
Wakasugi
K O
KO
Matsuoka
H
H
Hasegawa
H
H
D000818:Animals; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D007420:Intestine, Large / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013997:Time Factors
D001708:Biopterins; C003402:sapropterin