Susan M. Hutson

Professor of Biochemistry
B.A., Vanderbilt University, 1970
Ph.D. (Biochemistry), University of Wisconsin-Madison, 1976
Telephone: (336) 713-7217
E-mail: shutson@wfubmc.edu

There are three main research directions in my laboratory.

1) We are elucidating the signaling pathways that are activated by leucine and the role of key metabolic enzymes, the branched chain aminotransferase BCAT isozymes and the branched chain a-keto acid dehydrogenase (BCKD) enzyme complex in regulating the leucine signal.

2) We have discovered a novel redox-active dithiol/disulfide center in the mitochondrial BCATm, and found that this enzyme forms a redox-sensitive association with the E1 decarboxylase of the BCKD complex. We are currently determining the regulatory role of this "metabolon" and identifying the other protein components using mass spectrometry. We will also address the hypothesis that the BCAT isozymes have functions in addition to their metabolic role using proteomic technology to identify proteins that interact with the BCAT.

3) In a separate project we have proposed that excitatory neurotransmitter glutamate synthesis in the central nervous system is supported by a branched chain amino acid (BCAA) shuttle between astroglia and neurons that requires both BCAT isozymes. We have developed a knockout mouse for the glia-specific BCATm isozyme and will use antisense technology to knock down expression of the neuron-specific cytosolic BCATc Using x-ray crystallography we have determined the structural basis for the specificity of the antiepileptic drug gabapentin for BCATc.

Medical Relevance: Because of the medical consequences of blocking BCAA metabolism on brain function (Maple Syrup Urine Disease), increased use of high protein diets for general weight loss, and use of BCAA as supplements by performance athletes and body builders, it is imperative that we understand the molecular basis for effects of leucine on the body. Understanding how leucine regulates muscle protein mass may lead to new dietary interventions for muscle wasting syndromes.

Recent publications:

Berkich, D.A., Xu, Y., Lanoue, K.F., Gruetter, R., Hutson, S.M. Evaluation of brain mitochondrial glutamate and alpha-ketoglutarate transport under physiologic conditions. J. Neurosci. Res., 79:106-113 (2005).

Wajih, N., Sane, D. C., Hutson, S. M., Wallin, R.: Engineering of a recombinant vitamin K-dependent -carboxylation system with enhanced -carboxyglutamic acid (Gla) forming capacity: Evidence for a functional CXXC RedOx center in the system. J. Biol. Chem., 280:10540-10547 (2005).

Wajih, N., Hutson, S. M., Owen, J., Wallin, R.: Increased production of functional recombinant human clotting factor IX by BHK cells engineered to over express VKORC1, the vitamin K 2,3-epoxide reducing enzyme of the vitamin K cycle. J. Biol. Chem., 280:31603-31607 (2005).

Goto, M., Miyahara, I., Hirotsu, K., Conway, M., Yennawar, N., Islam, M. M., Hutson, S. M.: Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin. J. Biol. Chem., 280:37246-37256 (2005).

Hutson, S. M., Sweatt, A. J., LaNoue, K. F.: Branched-chain [corrected] amino acid metabolism: implications for establishing safe intakes. J. Nutr., 135(6 Suppl):1557S-1564S (2005).

Perez-Villasenor, G., Tovar, A. R., Moranchel, A. H., Hernandez-Pando, R., Hutson, S. M., Torres, N.: Mitochondrial branched chain aminotransferase gene expression in AS-30D hepatoma rat cells and during liver degeneration after partial hepatectomy in rat. Life Sci., 78:334-339 (2005).

Lynch, C. J., Gern, B., Lloyd, C., Hutson, S. M., Eicher, R., Vary, T. C. Leucine in food mediates some of the postprandial rise in plasma leptin concentrations. Am. J. Physiol. Endocrinol. Metab., 291(3):E621-E30 (2006).

Wajih N, Hutson SM, Wallin R. siRNA Silencing of Calumenin Enhances Functional Factor IX Production. Blood, 108:3757-60 (2006).

Hutson SM. The case for regulating indispensable amino acid metabolism: the branched-chain alpha-keto acid dehydrogenase kinase-knockout mouse. Biochem J. 400:e1-3 (2006).