Functional and metabolic changes in intestinal mucosa of rats after enteral administration of ornithine alpha-ketoglutarate salt.
BACKGROUND
Ornithine alpha-ketoglutarate salt efficiently improves the nutritional status of protein-depleted patients. Our aim was to explore the effects of ornithine alpha-ketoglutarate supplementation on intestinal physiology in healthy animals.


METHODS
Rats were given a nutritive mixture supplemented with ornithine alpha-ketoglutarate (1 g.kg-1 per day) by enteral route for 7 days. Controls received the diet supplemented with casein acid hydrolysate under isoenergetic and isonitrogenous conditions.


RESULTS
An adaptive hyperplasia of the villi and an increase in the brush-border hydrolase activities were observed in rats receiving ornithine alpha-ketoglutarate. Because of the high ornithine aminotransferase activity, ornithine alpha-ketoglutarate-derived ornithine was extensively transaminated with a concomitant enhancement of ornithine decarboxylation. Surprisingly, with glutamate and putrescine, the products of ornithine transamination and decarboxylation, gamma-aminobutyric acid accumulated (10-fold to 16-fold) dramatically in the intestinal mucosa of rats treated with ornithine alpha-ketoglutarate. Because gamma-aminobutyric acid formation was completely prevented by the diamine oxidase inhibitor aminoguanidine but was not modified after inactivation of ornithine aminotransferase by 5-fluoromethylornithine, it is evident that gamma-aminobutyric acid is formed in the mucosa from ornithine via putrescine as an intermediate.


CONCLUSIONS
It is assumed that enhanced gamma-aminobutyric acid formation in the intestinal mucosa by ornithine alpha-ketoglutarate treatment might be of physiologic importance in the regulatory processes of cell growth and differentiation.
Raul
F
F
Institut de Recherche contre les Cancers del l'Appareil Digestif, Hôpitaux Universitaires de Strasbourg, France.
Gosse
F
F
Galluser
M
M
Hasselmann
M
M
Seiler
N
N
D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D000818:Animals; D004750:Enteral Nutrition / Q000592:standards*; D005971:Glutamates / Q000032:analysis / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006867:Hydrolases / Q000032:analysis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D008871:Microvilli / Q000737:chemistry / Q000201:enzymology / Q000648:ultrastructure; D009952:Ornithine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011073:Polyamines / Q000032:analysis / Q000378:metabolism; D011700:Putrescine / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D005971:Glutamates; D006146:Guanidines; D011073:Polyamines; C002118:ornithine alpha-ketoglutarate; D005680:gamma-Aminobutyric Acid; D009952:Ornithine; D006867:Hydrolases; C004479:pimagedine; D011700:Putrescine