Hibernating animals and human infants contain brown fat deposits, so-called because of the presence of large numbers of mitochondria, the site of electron transport and oxidative phosphorylation. In brown fat, given the appropriate stimulus, oxidative phosphorylation and electron transport can be uncoupled, causing energy to be dissipated as heat. The protein responsible for the uncoupling is a brown fat inner mitochondrial membrane protein previously named UCP (for uncoupling protein), but now referred to as UCP1, since a second uncoupling protein has since been discovered. Previous experiments have shown that UCP1 protects against cold and is involved in regulation of energy expenditure. The ability of UCP1 to stimulate the consumption of calories solely for the production of heat led some investigators to postulate that UCP1 was involved in regulating body weight. Scientists have always wondered why some people seem to be able to ingest a large number of calories without gaining weight, whereas others eat moderately but are obese. If the UCP1 of brown fat were involved, scientists postulated that obese people would be efficient âburnersâ, whereas humans of moderate weight might burn calories inefficiently, releasing a greater proportion of energy as heat. But the role of UCP1 in humans has always been debated since infants contain a large amount of brown fat but mature adults do not. In order to examine the biochemical role of UCP1 more fully, the investigators in this case worked with mice referred to as knockouts. Knockout mice have been genetically engineered such that the gene coding for a particular protein is missing. By examining the characteristics of knockout mice, the biochemical and physiological roles of a particular protein can be ascertained. The investigators produced UCP1-knockout mice that are missing the gene for the UCP1 protein. They carried out experiments using these mice that are described below, studies that led to the discovery of a second uncoupling protein referred to as UCP2. The UCP2 protein may play a more significant role in obesity, since UCP2 is found in abundant amounts in white fat. References: Enerbäck, S., Jacobsson, A., Simpson, E. M., Guerra, C., Yamashita, H., Harper, M.-E., and Kozack, L.P. (1997) Nature 387, pp. 90-94. Fleury, C., Neverova, M., Collins, S., Raimbault, S., Champigny, O., Levi-Meyrueis, C., Bouillard, F., Seldin, M. F., Surwit, R. S., Ricquier, D., and Warden, C. H. (1997) Nature Genetics, 15, pp. 269-272. Lowell, B. B., S-Susulic, V., Hamann, A., Lawitts, J. A., Himms-Hagen, J., Boyer, B. B., Kozak, L. P., and Flier, J. S. (1993) Nature 366, pp. 740-742. Hirsch, J. (1997) Nature 387, pp. 27-28. 16.
Why is heat produced when UCP1 protein uncouples oxidative phosphorylation from electron transport?
