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Regulation of Rat Liver Branched-Chain -Keto Acid Dehydrogenase Activity by Meal Frequency and Dietary Protein^1,2,

Kevin P. Block^*,3, R. Paul Aftring^*,4 and Maria G. Buse^,*,5

^* Department of Medicine Department of Medicine Biochemistry, Medical University of South Carolina, Charleston, SC 29425

Effects of feeding frequency on liver branched-chain -keto acid dehydrogenase (BCKAD) activity are unknown. In the present study, rats were trained to consume their daily allotment of food in 6 h (meal-feeding). Rats were fed diets containing 0, 9, 25 or 50% casein and after 10 d were killed before or 3 h after the meal. The enzyme in rats fed diets containing 0, 9 and 25% casein was activated three- to sixfold after meal consumption. Previous studies showed that the liver enzyme is essentially fully activated in post-absorptive rats fed an adequate protein diet ad libitum. Meal-feeding an adequate protein (25% casein) diet resulted in a marked decrease in the postabsorptive percentage of active complex compared to ad libitum feeding of the same diet (29 ± 6% vs. 93 ± 6% active). Administration of -ketoisocaproate (200 µmol/100 g body weight, an inhibitor of BCKAD kinase) reversed the meal-feeding-induced inactivation of the complex within 10 min. We conclude that the frequency of food intake, in addition to the level of dietary protein, influences the proportion of liver BCKAD in the active state. Inactivation of hepatic BCKAD in rats trained to feed once a day may be an adaptive mechanism that results in increased efficiency of branched-chain amino acid utilization between meals.

KEY WORDS: • branched-chain amino acids • meal-feeding • protein • rats

¹ Presented in part at the 1987 Federation of American Societies for Experimental Biology meeting, Washington, D.C. [BLOCK, K. P., AFTRING, R. P. & BUSE, M. G. (1987) Effect of meal frequency and dietary protein on postabsorptive and postprandial activation of liver branched chain -keto acid dehydrogenase (BCKAD). Fed. Proc. 46: 752 (abs.)].

² Supported by grant DK-02001 from the National Institute of Diabetes, Digestive and Kidney Diseases, U.S. Public Health Service (to M.G.B.), and postdoctoral fellowships from the American Liver Foundation and the Medical University of South Carolina (to K.P.B.) and a Medical Scientist Training grant from the Medical University of South Carolina (to R.P.A.).

³ Present address: Department of Medicine, Beth Israel Hospital, Boston, MA.

⁴ Present address: Department of Medicine, Massachusetts General Hospital, Boston, MA.

⁵ To whom correspondence should be addressed.

Manuscript received 23 August 1989. Revision accepted 5 February 1990.

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