Susan M. Hutson, PhD
Professor, Biochemistry
Telephone: (336) 716-6055
Email: shutson@wfubmc.edu
Education:
- Vanderbilt University, BA, 1970
- University of Wisconsin (Madison), 1976, PhD: Biochemistry
Research Interests: Research in our laboratory is focused on identifying how amino acids 1) activate signaling pathways that stimulate protein synthesis and 2) regulate brain neurotransmitter synthesis.
Current Research:
There are three main research directions in my laboratory:
- We are elucidating the signaling pathways that are activated by leucine and the role of key metabolic enzymes, the branched chain aminotransferase (BCAT) (picture-BCAT) isozymes and the branched chain a-keto acid dehydrogenase (BCKD) enzyme complex (picture-BCKD) in regulating the leucine signal. (read more)
- We have discovered a novel redox-active dithiol/disulfide center in the mitochondrial BCATm (picture-CXXC), and found that this enzyme forms a redox-sensitive association with 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. (read more)
- 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 (picture-BCATc-neurons). We have developed a knockout mouse for the neuron-specific cytosolic BCATc and are using x-ray crystallography to determine the structural basis for the specificity of the antiepileptic drug gabapentin (picture-gabapentin) for BCATc. (read more)
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:
Perez-Villasenor G, Tovar AR, Moranchel AH, Hernandez-Pando R, Hutson SM, Torres N. Mitochondrial branched chain aminotransferase gene expression in AS-30D hepatoma rat cells and during liver regeneration after partial hepatectomy in rat.
Life Sci. 2005 Dec 12;78(4):334-9. Epub 2005 Sep 27.
Goto M, Miyahara I, Hirotsu K, Conway M, Yennawar N, Islam MM, Hutson SM. Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin.
J Biol Chem. 2005 Nov 4;280(44):37246-56. Epub 2005 Sep 1.
Wajih N, Hutson SM, Owen J, Wallin R. Increased production of functional recombinant human clotting factor IX by baby hamster kidney cells engineered to overexpress VKORC1, the vitamin K 2,3-epoxide-reducing enzyme of the vitamin K cycle. J Biol Chem. 2005 Sep 9;280(36):31603-7. Epub 2005 Jul 19.
Hutson SM, Sweatt AJ, Lanoue KF. Branched-chain [corrected] amino acid metabolism: implications for establishing safe intakes.
J Nutr. 2005 Jun;135(6 Suppl):1557S-64S. Review. Erratum in: J Nutr. 2005 Aug;135(8):2009.
Wajih N, Sane DC, Hutson SM, Wallin R. Engineering of a recombinant vitamin K-dependent gamma-carboxylation system with enhanced gamma-carboxyglutamic acid forming capacity: evidence for a functional CXXC redox center in the system.
J Biol Chem. 2005 Mar 18;280(11):10540-7. Epub 2005 Jan 7.
Publications:
For a listing of additional publications, refer to PubMed, a service provided by the National Library of Medicine