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Enzyme could provide continual fat burning

Houston--(March 29, 2001)--An enzyme discovered by Baylor College of Medicine researchers is critical to the metabolic pathway that governs the bodys ability to burn fat and could open a door into new ways to reduce obesity, diabetes and other fat-related human diseases.

In an article in the March 30 issue of the journal Science, Dr. Salih Wakil described mice, whose genes were manipulated to make them deficient in the enzyme acetyl-CoA carboxylase 2, or ACC2, as being able to eat as much as 40 percent more than normal mice and weigh 10 to 15 percent less.

ACC1 and ACC2 are involved in producing malonyl-CoA, which is key to the formation of fatty acids and to fat burning. Wakil, chairman of Baylors department of biochemistry and molecular biology, and his colleagues found that there are two pools of malonyl-CoA in the cell. The one in which ACC1 is important is critical to the formation of the long carbon chain component of fatty acids. The other pool associated with ACC2 regulates the transfer of fatty acids to the mitochondria, the cells powerhouse. Without AAC2, fat burns continuously in the mitochondria.

ACC2 was identified in Wakils laboratory in 1989 where researchers sequenced its DNA and located it on the chromosome. To determine the different effects of ACC1 and ACC2, Wakil and his colleagues created two forms of "knock-out" mice. The mice that lacked ACC1 died as embryos, demonstrating the value of fat in development.

"However, the mice genetically engineered to lack ACC2 seem very happy, live and breed well," Wakil said. The difference was that they ate more, weighed less and accumulated less fat than the normal animals.

Studies demonstrated that the ACC2-deficient mice had nearly one-half the fat of the normal mice. The fatty livers of normal mice looked pale compared to the bright red, virtually fat-free livers of the genetically engineered animals.

In one study, the researchers gave the ACC2-deficient mice insulin, whi
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Contact: Lynn Foltin
jfoltin@bcm.tmc.edu
713-798-4712
Baylor College of Medicine
28-Mar-2001


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