AJP - GI Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 297: G567-G575, 2009. First published July 1, 2009; doi:10.1152/ajpgi.00042.2009
0193-1857/09 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
297/3/G567    most recent
00042.2009v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Dasarathy, S.
Right arrow Articles by Kalhan, S. C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dasarathy, S.
Right arrow Articles by Kalhan, S. C.

LIVER AND BILIARY TRACT

Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion

Srinivasan Dasarathy,1,2 Takhar Kasumov,1 John M. Edmison,1,2 Lourdes L. Gruca,2 Carole Bennett,2 Clarita Duenas,2 Susan Marczewski,2 Arthur J. McCullough,1,2 Richard W. Hanson,2,3 and Satish C. Kalhan1,2

Departments of 1Gastroenterology and Hepatology, and 2Pathobiology, Cleveland Clinic, Lerner Research Institute, Cleveland; Department of 3Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio

Submitted 3 February 2009 ; accepted in final form 25 June 2009

The rates of oxidation of glycine and ureagenesis were quantified in the basal state and in response to an intravenous infusion of intralipid with heparin (IL) in healthy subjects (n = 8) and in subjects with nonalcoholic steatohepatitis (NASH) (n = 6). During fasting, no significant difference in weight-specific rate of appearance (Ra) of glycine, glycine oxidation, and urea synthesis was observed. Intralipid infusion resulted in a significant increase in plasma β-hydroxybutyrate in both groups. The correlation between free fatty acids and β-hydroxybutyrate concentration in plasma was 0.94 in NASH compared with 0.4 in controls, indicating greater hepatic fatty acid oxidation in NASH. Intralipid infusion resulted in a significant decrease in urea synthesis and glycine Ra in both groups and did not impact glycine oxidation. The fractional contribution of glycine carbon to serine was lower in subjects with NASH before and after IL infusion. In contrast, the fractional contribution of serine carbon to cystathionine was higher in NASH before and following IL infusion. These results suggest that hepatic fatty acid oxidation is higher in NASH compared with controls and that glycine oxidation and urea synthesis are not altered. An increase in oxidative stress, induced by a higher rate of fatty acid oxidation in NASH, may have caused an increase in the contribution of serine to cystathionine to meet the higher demands for glutathione.

glycine cleavage system; glutathione; fatty acid oxidation; ketones; serine; glycine; mitochondrial function; nonalcoholic fatty liver disease


Address for reprint requests and other correspondence: S. Kalhan, Dept. of Pathobiology, 9500 Euclid Ave., NE40, Cleveland, OH 44195 (e-mail: sck{at}case.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2009 by the American Physiological Society.