Lee McAlister-Henn, PhD

Adjunct Professor (Retired, UT Health San Antonio)


Ph.D. (1980) UT Southwestern Medical Center, Dallas
Post Doctoral: University of Connecticut, Farmington
University of California, Davis
Other Faculty Positions: Assistant/Associate Professor,
Biological Chemistry
School of Medicine
University of California, Irvine


RESEARCH EMPHASIS: molecular genetics; regulation of cellular respiratory rates; control of cellular redox levelsAllosteric Regulation of Energy Metabolism and Cellular Sources of NADPH for Antioxidant Function

Research in this laboratory uses molecular genetic approaches to analyze regulation of the intracellular redox environment. (A) A major area of investigation is the regulation of rates of oxidative metabolism at the level of allosteric regulation of mitochondrial NAD-specific isocitrate dehydrogenase (IDH), which catalyzes a rate-limiting step in the TCA cycle. We are constructing mutant forms of the enzyme in yeast to investigate the extent and importance of allosteric regulation in vivo.

We are also investigating the X-ray crystallographic structure of the enzyme (see Figure), which serves as an excellent model for the co-evolution of regulatory and catalytic ligand-binding sites and for fundamental principles involved in allostery. [This work is supported by NIH grant GM051265.] (B) In another major area, we have focused on two essential cytosolic sources of NADPH (the hexose monophosphate pathway and cytosolic NADP-specific isocitrate dehydrogenase).

Loss of both these sources results in a rapid decrease in viability of yeast cells under conditions when metabolic flux through the pathways of peroxisomal-oxidation or of mitochondrial respiration is increased. This decrease in viability is due to the accumulation of deleterious byproducts of these endogenous metabolic pathways due to inadequate production of NADPH for protective antioxidant enzyme systems. We have determined endogenous macromolecular targets of endogenous oxidative metabolic byproducts. [This work is supported by NIH grant AG017477.] (C)

In both these areas of investigation, we have developed techniques to quantify levels of various cellular metabolites and of reduced and oxidized forms of NAD(P) cofactors. These measurements have led to an understanding of dramatic and rapid changes that can occur in the cellular redox environment, and they have led to major new hypotheses related to signaling events that control rates of flux through central metabolic pathways and to the impact of changes in metabolic flux to the extension of life span.