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Am J Physiol Endocrinol Metab 277: E352-E360, 1999;
0193-1849/99 $5.00
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Vol. 277, Issue 2, E352-E360, August 1999

Calories and aging alter gene expression for gluconeogenic, glycolytic, and nitrogen-metabolizing enzymes

Joseph M. Dhahbi1, Patricia L. Mote1, John Wingo1, John B. Tillman1, Roy L. Walford2, and Stephen R. Spindler1

1 Department of Biochemistry, University of California, Riverside 92521; and 2 Department of Pathology, School of Medicine, University of California, Los Angeles, California 90024

We characterized the effects of calorie restriction (CR) on the expression of key glycolytic, gluconeogenic, and nitrogen-metabolizing enzymes in mice. Of the gluconeogenic enzymes investigated, liver glucose-6-phosphatase mRNA increased 1.7- and 2.3-fold in young and old CR mice. Phosphoenolpyruvate carboxykinase mRNA and activity increased 2.5- and 1.7-fold in old CR mice. Of the key glycolytic enzymes, pyruvate kinase mRNA and activity decreased ~60% in CR mice. Hepatic phosphofructokinase-1 and pyruvate dehydrogenase mRNA decreased 10-20% in CR mice. Of the genes that detoxify ammonia generated from protein catabolism, hepatic glutaminase, carbamyl phosphate synthase I, and tyrosine aminotransferase mRNAs increased 2.4-, 1.8-, and 1.8-fold with CR, respectively. Muscle glutamine synthetase mRNA increased 1.3- and 2.1-fold in young and old CR mice. Hepatic glutamine synthetase mRNA and activity each decreased 38% in CR mice. These CR-induced changes are consistent with other studies suggesting that CR may decrease enzymatic capacity for glycolysis and increase the enzymatic capacity for hepatic gluconeogenesis and the disposal of byproducts of muscle protein catabolism.

calorie restriction; enzyme activity; metabolism; mice; mRNA


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