title: First-pass metabolism limits the intestinal absorption of enteral alpha-ketoglutarate in young pigs.
abstract: Our results in a previous study indicated that the portal absorption of intragastrically fed alpha-ketoglutarate (AKG) was limited in young pigs. Our aim was to quantify the net portal absorption, first-pass metabolism, and whole-body flux of enterally infused AKG. In study 1, we quantified the net portal nutrient absorption in young pigs (n = 9) given an intraduodenal infusion of milk replacer [10 mL/(kg . h)] and either saline (control) or 930 micromol/(kg . h) AKG for 4 h. In study 2, we quantified the luminal disappearance of a duodenal AKG bolus in young pigs (n = 7). In study 3, we quantified the whole-body kinetics of (13)C-AKG metabolism when infused either enterally (n = 9) or intravenously (n = 9) in young pigs. In study 1, when compared with the control group, enteral AKG infusion increased (P < 0.01) the arterial (13.8 +/- 1.7 vs. 27.4 +/- 3.6 micromol/L) and portal (22.0 +/- 1.4 vs. 64.6 +/- 5.9 micromol/L) AKG concentrations and the net portal absorption of AKG [19.7 +/- 2.8 vs. 95.2 +/- 12.0 micromol/(kg . h)]. The mean fractional portal appearance of enterally infused AKG was 10.23 +/- 1.3%. In study 2, the luminal disappearance of AKG was 663 micromol/(kg . h), representing 63% of the intraduodenal dose. In study 3, the whole-body (13)C-AKG flux [4685 +/- 666 vs. 801 +/- 67 micromol/(kg . h)] was higher (P < 0.05) when given enterally than intravenously, but (13)CO(2) recovery was not different (37.3 +/- 1.0 vs. 36.2 +/- 0.7%dose). The first-pass splanchnic (13)C-AKG utilization was approximately 80%, of which 30% was oxidized to (13)CO(2). We conclude that the intestinal absorption of AKG is limited in young pigs largely due to substantial first-pass gastrointestinal metabolism.
authors.affiliation: U.S. Department of Agriculture/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Barry D
authors.initials: BD
authors.lastname: Lambert
authors.forename: Rafal
authors.initials: R
authors.lastname: Filip
authors.forename: Barbara
authors.initials: B
authors.lastname: Stoll
authors.forename: Peter
authors.initials: P
authors.lastname: Junghans
authors.forename: Michael
authors.initials: M
authors.lastname: Derno
authors.forename: Ulf
authors.initials: U
authors.lastname: Hennig
authors.forename: Wolfgang B
authors.initials: WB
authors.lastname: Souffrant
authors.forename: Stefan
authors.initials: S
authors.lastname: Pierzynowski
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Burrin
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D004750:Enteral Nutrition; D005260:Female; D007408:Intestinal Absorption; D007656:Ketoglutaric Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D013552:Swine
chemical_list: D002247:Carbon Isotopes; D007656:Ketoglutaric Acids; D002245:Carbon Dioxide