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Mitochondrial Storage Forms of Acetyl CoA Carboxylase: Mobilization/Activation Accounts for Increased Activity of the Enzyme in Liver of Genetically Obese Zucker Rats^1,2,

Laboratory of Metabolic Regulation, Department of Food Science and Nutrition, Ohio State University, Columbus, OH 43210

In earlier reports, we have described a previously unrecognized mechanism which regulates the activity of acetyl CoA carboxylase in rat liver by the control of its distribution between relatively inactive mitochondrial and active cytosolic forms. In this study, the activity, total quantity and the subcellular distribution of acetyl CoA carboxylase were determined in liver of fed and fasted (48 h) homozygous obese (fa/fa) zucker rats and homozygous lean (Fa/Fa) littermates. The results indicate that neither diet nor genetic obesity affected the total quantity of acetyl CoA carboxylase per unit weight of liver. Instead, increased activity of this enzyme in the liver of the Zucker rat was primarily due to a shift in the subcellular distribution away from relatively inactive mitochondrial forms toward active cytosolic forms. Thus, the Zucker rat appears to be yet another example illustrating the physiological importance of regulating the activity of acetyl CoA carboxylase by controlling its subcellular distribution.

KEY WORDS: • acetyl CoA carboxylase • mitochondrial acetyl CoA carboxylase • Zucker rats

¹ Supported in part by grants from the Ohio affiliate of the American Heart Association and the National Institutes of Health (Grant HL35384). Salaries and research support were also provided in part by state and federal funds appropriated to the Ohio Agricultural Research and Development Center, Ohio State University, manuscript number 137-88.

² Presented in part at the 71st Annual Meeting, Federation of American Societies for Experimental Biology, April 2, 1987 [Allred, J. B., Roman-Lopez, C. R., Jurin, R. R. & McCune, S. A. (1987) Fed. Proc. 46: 1416 (abs.)].

Manuscript received 13 May 1988. Revision accepted 2 December 1988.