Journal of Nutrition

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Journal of Nutrition Vol. 120 No. 11 November 1990, pp. 1376-1386
Copyright © 1990 by American Society for Nutrition
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Pantothenate Kinase Activity in Livers of Genetically Diabetic Mice (db/db) and Hormonally Treated Cultured Rat Hepatocytes1, 2,

Nancy Kirschbaum, Robin Clemons, Kathleen A. Marino, Gina Sheedy, Minh Ly Nguyen and Colleen M. Smith3

Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140

Preparations from livers of fed and fasted genetically diabetic and nondiabetic mice (C57BL/KsJ db/db, db/+, or +/+) were used to determine whether changes in pantothenate kinase activity and/or properties corresponded to hormonally directed changes in liver total CoA content. Livers of fasted, nondiabetic mice had ratios of pantothenate kinase (PAK) to lactate dehydrogenase (LDH) activity 1.6 times values for fed nondiabetic controls, and they had a total CoA content per milligram of DNA that was 1.8 times control values. Livers of fed genetically diabetic mice had values for PAK/LDH and total CoA per milligram of DNA that were 1.5 and 2.8 times, respectively, those of nondiabetic controls. Liver PAK from genetically diabetic mice was inhibited by acetyl-CoA to the same extent as enzyme from nondiabetic mice and by CoASH to nearly the same extent. Rat hepatocytes in primary culture incubated with dibutyryl cAMP + theophylline + dexamethasone had PAK/LDH levels 1.5 times those of cells not treated with hormonal effectors, and PAK was inhibited to the same extent by acetyl-CoA and nearly the same extent by CoASH. The data show an increase in extractable hepatic PAK activity under conditions in which the total CoA content is elevated, and they suggest that glucocorticoids and cAMP levels contribute to the increased PAK activity.


KEY WORDS: • pantothenate • coenzyme A • glucocorticoids • diabetic • mice • rat hepatocytes

1 The authors dedicate this manuscript to the memory of Lucille S. Hurley, in gratitude for her contribution to our knowledge of pantothenate deficiency.

2 Supported by a grant from the National Institute of Arthritis, Metabolism and Digestive and Kidney Diseases (AM18045) to C. M. Smith.

3 Reprint requests should be addressed to Dr. Colleen M. Smith, Dept. of Biochemistry, Temple University School of Medicine, 3420 N. Broad St., philadelphia, PA 19140.

Manuscript received 23 January 1989. Revision accepted 1 June 1990.







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