Relationship between the concentrations of glycolytic intermediates and expression of the L-type pyruvate kinase gene in cultured hepatocytes.
Previous studies have suggested that some glycolytic intermediates are involved in the regulation of L-type pyruvate kinase gene expression by carbohydrates such as glucose and fructose. To find such intermediates, we examined the relationship between the levels of L-type pyruvate kinase mRNA and glycolytic metabolites in hepatocytes cultured under various conditions. Of the metabolites, the levels of 3-phosphoglycerate and phosphoenol-pyruvate only increased significantly under conditions under which the expression of the L-type pyruvate kinase gene was stimulated. The level of glucose 6-phosphate, which was reported to be involved in dietary stimulation of this gene expression, was not correlated with the mRNA level since marked accumulation of deoxyglucose 6-phosphate occurring on the addition of deoxyglucose, a nonmetabolizable glucose analog, was not accompanied by an increase in the L-type pyruvate kinase mRNA level. In addition, we found that fructose at a low concentration in the presence of glucose failed to increase the mRNA and metabolite levels in contrast to other reports that the promoter activity of the L-type pyruvate kinase gene is stimulated by this treatment. Thus we propose that 3-phosphoglycerate and/or phosphoenolpyruvate are involved in the carbohydrate regulation of L-type pyruvate kinase gene expression.
Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Suita.
R
R
Kang
K
K
Yamada
T
T
Tanaka
T
T
Lu
T
T
Noguchi
D000818:Animals; D002478:Cells, Cultured; D005632:Fructose / Q000378:metabolism* / Q000494:pharmacology; D005636:Fructosephosphates / Q000032:analysis / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008099:Liver; D010728:Phosphoenolpyruvate / Q000032:analysis / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic
D005636:Fructosephosphates; D007328:Insulin; D012333:RNA, Messenger; D005632:Fructose; C027618:fructose-6-phosphate; D010728:Phosphoenolpyruvate; D011770:Pyruvate Kinase; D005947:Glucose