Mechanism of delayed hepatic glycogen synthesis after an oral galactose load vs. an oral glucose load in adult rats.
We have compared the effects of administration of oral galactose or glucose (1 g/kg) to 24-h fasted rats to examine the mechanism by which galactose regulates its own incorporation into liver glycogen in vivo. Liver glycogen increased to a maximum more slowly after galactose than after glucose administration (0.14 vs. 0.29 mumol.g liver-1.min-1). Glycogen accumulation after the galactose load was 70% of that after the glucose load (149 vs. 214 mumol), and the net increase in liver glycogen represented the same proportion (24 vs. 22%) of added carbohydrate after urinary loss of galactose was accounted for. Slower glycogen accumulation after galactose vs. glucose loading could not be explained by galactosuria, by differences in the active forms of synthase or phosphorylase, by end product (glycogen) inhibition of synthase phosphatase, or by different concentrations of the known allosteric effectors of synthase R plus I and phosphorylase a. Similar increases in glucose 6-phosphate were observed after both hexoses. AMP and ADP increased only transiently after galactose administration, and ATP, UTP, and Pi concentrations were unchanged. The UDP-glucose concentration decreased, whereas the UDP-galactose concentration increased two- to threefold after galactose but not glucose administration. The UDP-glucose pyrophosphorylase reaction is inhibited competitively by UDP-galactose. This could explain the decreased UDP-glucose concentration and the reduced rate of glycogen synthesis after galactose was given.
Niewoehner
C B
CB
Endocrine Metabolic Section, Veterans Affairs Medical Center, Minneapolis 55417.
Neil
B
B
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005690:Galactose / Q000493:pharmacokinetics / Q000494:pharmacology*; D005693:Galactosemias / Q000097:blood; D005947:Glucose / Q000493:pharmacokinetics / Q000494:pharmacology*; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001786:Blood Glucose; D006003:Glycogen; D006006:Glycogen Synthase; D005947:Glucose; D005690:Galactose