First-pass metabolism limits the intestinal absorption of enteral alpha-ketoglutarate in young pigs

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 mu mol/(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 C-13-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 mu mol/L) and portal (22.0 +/- 1.4 vs. 64.6 +/- 5.9 mu mol/L) AKG concentrations and the net portal absorption of AKG [19.7 +/- 2.8 vs. 95.2 +/- 12.0 mu mol/(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 mu mol/(kg . h), representing 63% of the intraduodenal dose. In study 3, the whole-body C-13-AKG flux [4685 +/- 666 vs. 801 +/- 67 mu mol/(kg . h)] was higher (P < 0.05) when given enterally than intravenously, but (CO2)-C-13 recovery was not different (37.3 +/- 1.0 vs. 36.2 +/- 0.7% dose). The first-pass splanchnic C-13-AKG utilization was similar to 80%, of which 30% was oxidized to (CO2)-C-13. We conclude that the intestinal absorption of AKG is limited in young pigs largely due to substantial first-pass gastrointestinal metabolism.