| Title | Glycine and urea kinetics in non-alcoholic steatohepatitis in human: effect of intralipid infusion. | | Author(s) | Dasarathy S, Kasumov T, Edmison JM, Gruca LL, Bennett C, Duenas C, Marczewski S, McCullough AJ, Hanson RW, Kalhan SC | | Institution | MetroHealth Medical Center. | | Source | Am J Physiol Gastrointest Liver Physiol 2009 Jul 1. | | Abstract | The rate 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 non-alcoholic 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 beta-hydroxybutyrate in both groups. The correlation between free fatty acids and beta-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 in order to meet the higher demands for glutathione. Key words: glycine cleavage system, urea, glutathione, ketones. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19571235 |
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