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Artist’s rendering of isocitrate dehydrogenase is on the cover of the Journal of Biological Chemistry.
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SAN ANTONIO (April 24, 2008) — Biochemists at The University of Texas Health Science Center at San Antonio have deciphered the three-dimensional, atomic-level structure of an enzyme that acts as a ‘fuel gauge,’ sensing when cells are low in energy and signaling it is time to refuel.

X-ray crystallography helped identify the structure
The scientists worked out the 3-D contour of the enzyme, called isocitrate dehydrogenase or IDH, by coaxing it to form single crystals and subsequently bombarding the crystals with X-rays. The X-ray diffraction pattern was carefully measured and advanced software was used to interpret the resulting diffraction patterns. This technique is called X-ray crystallography and is a specialty of P. John Hart, Ph.D., in the UT Health Science Center’s Department of Biochemistry.

Artist’s rendering of organism on cover of journal
This is the first time the IDH structure has been unveiled in an organism above a bacterium, in this case yeast. A rendering of IDH is featured on the cover of the April 18 issue of the Journal of Biological Chemistry (JBC).

IDH plays major role in energy production in cells
“This is a tremendously exciting discovery because IDH is a central player in cells’ energy production,” said JBC article lead author Lee McAlister-Henn, Ph.D., professor and deputy chair of the Department of Biochemistry. She joined the Health Science Center in 1992 from the University of California, Irvine and has worked on IDH for two decades. Dr. Hart is a co-author of the JBC article.

IDH participates in production of adenosine triphosphate, the most important form of cellular energy. This energy production cycle takes place in mitochondria, which are the factories or power plants located in cells.

Lee McAlister-Henn, Ph.D., professor and deputy chair of the Department of Biochemistry, has worked on IDH for 20 years.

Goal is to eventually study IDH in humans
“IDH is a key metabolic enzyme and nobody has understood how it works as a fuel gauge,” Dr. McAlister-Henn said. “We will now make mutant forms of IDH to test examples of poor regulation, and ultimately the goal will be to extend studies to human IDH.”

IDH may play a key role in metabolic diseases such as Type 2 diabetes, but Dr. McAlister-Henn declined to speculate on what the future clinical implications of the current finding will be.

The Robert A. Welch Foundation, one of the nation's oldest and largest sources of private funding for basic chemistry research, and the National Institutes of Health’s National Institute of General Medical Sciences funded the research, along with the Health Science Center’s Office of the Vice President for Research.

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The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $576 million, the Health Science Center is the chief catalyst for the $15.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $35 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 23,000 graduates (physicians, dentists, nurses, scientists and allied health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, allied health, dentistry and many other fields. For more information, visit www.uthscsa.edu.