|BUSH, JILL - BAYLOR COLLEGE OF MEDICIN
|GUOYAO, WU - TEXAS A & M UNIVERSITY
|SURYAWAN, AGUS - BAYLOR COLLEGE OF MEDICIN
|NGUYEN, HANH - BAYLOR COLLEGE OF MEDICIN
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/9/2001
Publication Date: 1/1/2002
Citation: Bush, J.A., Guoyao, W., Suryawan, A., Nguyen, H.V., Davis, T.A. 2002. Somatotropin-induced amino acid conservation in pigs involves differential regulation of liver and gut urea cycle enzyme activity. Journal of Nutrition. 132(1):59-67.
Interpretive Summary: Somatotropin (ST) is a growth hormone that, when administered to animals, improves their growth, increases protein and lean body mass, and reduces fat. ST conserves amino acids, reduces the production of urea (a urinary compound that is the end product of protein breakdown), and decreases nitrogen loss in urine. We wanted to determine the mechanism underlying this decrease in urea production, which occurs mostly in the liver but also in the gut when urea cycle enzymes convert ammonia and bicarbonate, the products of protein and amino acid degradation. We theorized that the ST-improved amino acid conservation involves a regulation of the activity levels of urea cycle enzymes in the liver and gut. We treated growing swine with ST for 7 days, infused the fed pigs with bicarbonate followed by phenylalanine, an amino acid, and took multiple samples and measurements. Our results showed that ST reduced the blood urea nitrogen as well as the oxidation of phenylalanine. The activity levels of these key enzymes were reduced in the liver, but not in the gut. We conclude the ST-induced decrease in amino acid breakdown involves a reduction in the activity of urea cycle enzymes in the liver, so less urea is produced. We also find that ST treatment effects a tissue-specific regulation of these enzymes, based on the different results in the liver and gut. These valuable findings increase researchers' understanding of hormonal actions with regard to increased nitrogen retention and preservation of protein available to stave off muscle loss and enable growth. Thus, this study in the pig, a laboratory model for the human, may someday improve the treatment of young patients who may be given growth hormone in certain cases of stunted growth or burn injuries.
Technical Abstract: Somatotropin (ST) treatment promotes animal growth and allows for the conservation of amino acids by increasing nitrogen retention and reducing ureagenesis and amino acid oxidation. To determine whether the improvement in amino acid conservation with ST treatment involves regulation of urea cycle enzyme activities in liver and intestine,growing swine were treated with either ST or saline for 7d. Fed pigs were infused intravenously for 2h with NaH**13C03 followed by an intraduodenal infusion of [1**-13C] phenylalanine. Arterial and portal venous blood and breath samples were obtained at baseline and steady-state conditions for measurement of amino acid and blood urea nitrogen (BUN) concentrations and whole-body phenylalanine oxidation. Urea cycle activities were determined in liver and jejunum. ST decreased BUN, arterial and portal venous amino acid concentrations and whole-body phenylalanine oxidation. The activities of carbamoylphosphate synthase-1,argininosuccinate synthase, argininosuccinat lyase, arginase, and glutaminase,but not of ornithine carbamoyltransferase, ornithine aminotransferase, or glutamate dehydrogenase were reduced in liver of ST-treated pigs. ST slightly increased intestinal activity of glutaminase, but did not affect that of any other enzymes. ST decreased hepatic, but increased jejunal, N-acetylglutamate and carbamoylphosphate content. These results demonstrate that the reduced amino acid catabolism with ST treatment in growing pigs involves a reduction in hepatic urea cycle enzyme activities. The effect of ST treatment on porcine urea cycle enxzymes is tissue-specific and is associated with a reduction in substrate availability for hepatic ureagenesis.