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

item Burrin, Douglas - Doug

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2006
Publication Date: 11/1/2006
Citation: Lambert, B.D., Filip, R., Stoll, B., Junghans, P., Derno, M., Hennig, U., Souffrant, W.B., Pierzynowski, S., Burrin, D.G. 2006. First-pass metabolism limits the intestinal absorption of enteral alpha-ketoglutarate in young pigs. Journal of Nutrition. 136:2779-2784.

Interpretive Summary: Alpha-ketoglutarate (AKG) is an intermediate formed during the metabolism of the amino acid glutamate, which is abundant in many foods and additives in the form of monosodium glutamate. Glutamate is important for human infant health since it is a major fuel for the gut or small intestine. Because AKG is formed during glutamate metabolism, we wanted to test whether dietary AKG is also extensively metabolized as a fuel for the gut. Our previous studies suggested that only a limited amount of dietary AKG is actually absorbed into the body when fed to young pigs. We further tested this question in a series of studies in young pigs where we measured the rate of AKG directly absorbed from the gut and also quantified its metabolism by giving dietary AKG in a chemical form (13C-labeled AKG), known as a stable isotope, that can be traced through the body. Our results showed that nearly all (80%) of the AKG consumed in the diet is metabolized by the gut. We also showed that most of the AKG ingested is rapidly taken up by mucosal cells that line the intestine and disappears rapidly from the lumen of the gut. A large portion (30%) of the AKG metabolized by the gut is completely converted to CO2, which implies that it is used as an important energy fuel for the intestine, similar to that of glutamate. These studies show that AKG can serve as a useful substitute or dietary supplement to provide a specific energy source for the developing gut in infants.

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