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 [micro]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 [sup.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 [+ or -] 1.7 vs. 27.4 [+ or -] 3.6 [micro]mol/L) and portal (22.0 [+ or -] 1.4 vs. 64.6 [+ or -] 5.9 [micro]mol/L) AKG concentrations and the net portal absorption of AKG [19.7 [+ or -] 2.8 vs. 95.2 [+ or -] 12.0 [micro]mol/(kg * h)]. The mean fractional portal appearance of enterally infused AKG was 10.23 [+ or -] 1.3%. In study 2, the luminal disappearance of AKG was 663 [micro]mol/(kg * h), representing 63% of the intraduodenal dose. In study 3, the wholebody [sup.13]C-AKG flux [4685 [+ or -] 666 vs. 801 [+ or -] 67 [micro]mol/(kg * h)] was higher (P < 0.05) when given enterally than intravenously, but [sup.13]C[O.sub.2] recovery was not different (37.3 [+ or -] 1.0 vs. 36.2 [+ or -] 0.7%dose). The first-pass splanchnic [sup.13]C-AKG utilization was ~80%, of which 30% was oxidized to [sup.13]C[O.sub.2]. We conclude that the intestinal absorption of AKG is limited in young pigs largely due to substantial first-pass gastrointestinal metabolism.