Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion.
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 (R(a)) 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 R(a) 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.
Dasarathy
Srinivasan
S
Department of Gastroenterology and Hepatology, Lerner Research Institute, Cleveland, USA.
Kasumov
Takhar
T
Edmison
John M
JM
Gruca
Lourdes L
LL
Bennett
Carole
C
Duenas
Clarita
C
Marczewski
Susan
S
McCullough
Arthur J
AJ
Hanson
Richard W
RW
Kalhan
Satish C
SC
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003540:Cystathionine / Q000097:blood; D005215:Fasting / Q000097:blood; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000097:blood; D005998:Glycine / Q000097:blood*; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019518:Postprandial Period; D012694:Serine / Q000097:blood; D014508:Urea / Q000097:blood*; D055815:Young Adult
D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D003540:Cystathionine; D012694:Serine; D014508:Urea; D005978:Glutathione; D005998:Glycine; D020155:3-Hydroxybutyric Acid