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Am J Physiol Gastrointest Liver Physiol 296: G1130-G1139, 2009. First published February 19, 2009; doi:10.1152/ajpgi.90545.2008
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LIVER AND BILIARY TRACT

Threonine-deficient diets induced changes in hepatic bioenergetics

Catherine M. Ross-Inta, Yi-Fan Zhang, Andrew Almendares, and Cecilia Giulivi

Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, California

Submitted 12 September 2008 ; accepted in final form 16 February 2009

Diets deficient in an indispensable amino acid are known to suppress food intake in rats. Few studies were focused at understanding how amino acid-deficient diets may elicit biochemical changes at the mitochondrial level. The goal of this study was to evaluate mitochondrial function in rats fed diets with 0.00, 0.18, 0.36, and 0.88% threonine (Thr) (set at 0, 30, 60, and 140% of Thr requirement for growth). Here, it is described for the first time that Thr-deficient diets induce a specific uncoupling of mitochondria in liver, especially with NADH-linked substrates, not observed in heart (except for Thr-devoid diet). The advantage of this situation would be to provide ATP to support growth and maintenance when high-quality protein food (or wealth of high-quality food in general) is available, whereas Thr-deficient diets (or deficient-quality protein food) promote the opposite, increasing mitochondrial uncoupling in liver. The uncoupling with NADH substrates would favor the use of nutrients as energy sources with higher FADH-to-NADH ratios, such as fat, minimizing the first irreversible NADH-dependent catabolism of many amino acids, including Thr, thus enhancing the use of the limiting amino acid for protein synthesis when a low quality protein source is available.

mitochondria; oxidative stress; oxygen consumption; oxidative phosphorylation; amino acid imbalance; amino acid deficiency



Address for reprint requests and other correspondence: C. Giulivi, Univ. of California Davis, Dept. Molecular Biosciences, 1311 Haring Hall, One Shields Ave., Davis, CA 95616 (e-mail: cgiulivi{at}ucdavis.edu)







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