University of Pittsburgh researchers crack code of 3-D structure in key metabol...( PITTSBURGH March 10 Using X-ray cry...),Health

PITTSBURGH, March 10 Using X-ray crystallography, researchers at the University of Pittsburgh School of Medicine led by structural biologist Joanne I. Yeh, Ph.D., have become the first to decipher the three-dimensional structure of a membrane-bound enzyme that plays a crucial role in glycerol metabolism a discovery that could lead to important advances against obesity, diabetes and a potential host of other diseases. Their findings are reported in the March 4 issue of the Proceedings of the National Academy of Sciences.

The sugar-alcohol glycerol is an essential source of energy that is required to help drive cellular respiration. In addition to powering some of the most central reactions of the body, glycerol also provides key precursors needed to regulate fatty acid and sugar metabolism. Figuring out the complex ways that cells break down or produce glycerol and use this vital chemical could be critical to combating obesity, diabetes and other chronic disorders. Recent findings also have linked glycerol metabolism to cellular processes related to aging, infectivity in certain organisms such as Mycobacterium tuberculosis, and in other energy-related illnesses.

Everybody wants a golden bullet for obesity, and certainly we need better ways of controlling diabetes, said Dr. Yeh, the studys senior author and associate professor of structural biology at Pitt. I think that glycerol metabolism will be on the forefront of developing treatments for these diseases, and so many others, since it is a pivotal yet underappreciated link among some very important metabolic pathways.

The protein structure Dr. Yehs team solved is a large enzyme called Sn-glycerol-3-phosphate dehydrogenase known simply as GlpD found in abundance in the cell membranes of almost all organisms, including humans. GlpD is a monotopic membrane protein, which means that although it is embedded partially into the cell membrane, the protein does not span the entire membran
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