Biomedical Summer Undergraduate Research Experience Program
(B-SURE)
The University of Texas Health Science Center at San Antonio (UTHSCSA)
McALISTER-HENN,
Lee (Biochemistry): The fundamental aim
of research in this laboratory is to utilize the yeast molecular genetic
system to analyze controls of energy metabolism in eukaryotic cells.
We are focusing on the family of isocitrate dehydrogenase enzymes with
genetically distinct representatives in three different cellular compartments.
Major goals are focused on understanding the regulation of flux through
the tricarboxylic acid cycle controlled by mitochondrial NAD+-specific
isocitrate dehydrogenase (IDH). This complex allosteric enzyme is
composed of four each of two different types of subunits, one with primarily
regulatory function and the other with primarily catalytic function.
Current goals are to understand fundamentals of the structure of this enzyme
(using X-ray crystallography) to facilitate construction of mutant
forms of the enzyme that lack key elements of regulated catalysis.
These mutant forms of IDH will then tested in vivo to ascertain effects
on rates of energy metabolism.
Other major goals focus on the physiological contributions
of three distinct but highly homologous NADP+-specific isocitrate dehydrogenases
differentially located in mitochondria (IDP1), in the cytosol (IDP2), and
in peroxisomes (IDP3). One very important contribution under investigation
is the essential role of each isozyme in maintaining compartmental levels
of NADPH reducing equivalents needed for biosynthetic reactions and for
thiol-dependent antioxidant enzyme systems. Current efforts include
analyses of single and multiple gene disruption mutants, including assessment
of detrimental effects in each cellular compartment due to loss of the
corresponding IDP isozyme.
Lee McAlister-Henn's Web Page.