Glutamine and its derivatives e.g., alpha-ketoglutaric acid (AKG) or ornithine-alpha-ketoglutarate (OKG) are molecules with a central role (via the Krebs cycle) in systemic, intestinal and gut bacterial metabolism. Studies have shown that AKG is a precursor not only of glutamine and arginine, but also of some other keto acids e.g., alpha-ketoisocaproate which in turn is a precursor of hydroxy-methyl-butyrate, which itself is regarded as a protein catabolic protector. Recently it has been postulated that AKG is not only an important energy donor, but that it also functions as an ammonium ion scavenger via transformation to glutamate, ornithine and putrescine and finally to GABA or succinate. Several beneficial effects of AKG have been reported in human medicine e.g., improved patients' recovery following gastrointestinal surgery. On the other hand, is was reported that 100 per cent glutamate metabolism in the first pass in infant pigs' small intestine. In the current presentation we discuss the potential benefits of using glutamine derivatives in human clinical nutrition as well as their role as feed additives in the production of farm animals.KEY WORDS: feed additives, glutamine, alpha-keto-glutarate METABOLIC AND PHYSIOLOGICAL EFFECTS OF GLUTAMINE AND ITS DERIVATIVESIn certain physiological and pathological conditions associated with acute or chronic malnutrition and/or hormonal stress, the human body shows signs of increased protein degradation or decreased protein synthesis, or both (Ahlman et al.,

To study the absorption, metabolism and kinetics, the AKG (in different concentrations) was administered intravenously, intra-portally, orally and directly into the ileum or duodenum of pigs, chronically fitted with portal and jugular catheters and T-shaped cannula at the duodenum and ileum. Additionally, this study was conducted to determine the influence of low pH, Fe(2+) or/and SO on AKG gut absorption and conversely FeSO(4) and FeSO(4)/AKG on Fe(2+) gut absorption. It is concluded that AKG was significantly better absorbed from the upper small intestine than from the distal sections. Furthermore, low pH, Fe(2+) and/or SO ions enhanced AKG absorption. The AKG administered to the portal vein was rapidly eliminated from the blood (half-life less than 5 min). The short lifetime for AKG is probably dependent on quick metabolism in the enteorcyetes and liver. However, the prolonged half-life can be related to its low AKG blood concentration. The Fe(2+) concentrations in blood increased after FeSO(4) and FeSO(4)/AKG duodenal infusion. The implication of above observations is important for practical application of the AKG in animal and human nutrition as well in medicine.

Limitations in efficacy and/or tolerance of currently available urate-lowering therapies (ULTs), such as oral xanthine oxidase inhibitors, uricosurics, and intravenous uricase agents contribute to the development of refractory gout. Renal excretion is the major route of uric acid elimination, but the intestinal tract plays an increasingly recognized role in urate homeostasis, particularly in chronic kidney disease (CKD) in which the renal elimination of urate is impaired. We targeted intestinal degradation of urate in vivo with ALLN-346, an orally administered, engineered urate oxidase, optimized for proteolytic stability, and activity in the gut. We tested ALLN-346 in uricase/urate oxidase deficient mice (URKO mice) with severe hyperuricemia, hyperuricosuria, and uric acid crystalline obstructive nephropathy. A total of 55 male and female URKO mice were used in the two consecutive studies. These seminal, proof-of-concept studies aimed to explore both short- (7-day) and long-term (19-day) effects of ALLN-346 on the reduction of plasma and urine urate. In both the 7- and 19-day studies, ALLN-346 oral therapy resulted in the normalization of urine uric acid excretion and a significant reduction of hyperuricemia by 44 and 28% when therapy was given with food over 24 h or was limited for up to 6 h, respectively. Fractional excretion of uric acid (FEUA) was normalized with ALLN-346 therapy. Oral enzyme therapy with engineered urate oxidase (ALLN-346) designed to degrade urate in the intestinal tract has the potential to reduce hyperuricemia and the renal burden of filtered urate in patients with hyperuricemia and gout with and without CKD.