Zigging and ZAGing
Dateline: 03/25/99
The structure of a fat-depleting protein known as ZAG (Zn-a2-glycoprotein) may lead to the development of a new class of drugs for treating clinical obesity. In a recently published study, ZAG appears to accelerate fat loss in patients with severe diseases. ZAG occurs naturally in almost all body fluids, inclusive of saliva, sweat, urine and blood.
During the last year, researchers discovered that ZAG was involved in a wasting syndrome known as cachexia. Cachexia is most often associated with people who have a terminal illness such as AIDS or cancer. Cachexia leads to rapid weight loss including the loss of both muscle and fat tissue.
If ZAG is introduced into fat cells, the cells will breakdown lipids, a major part of most body fats. Likewise, when it was fed to rats, the rats lost weight even though their caloric consumption remained the same. The researchers are hopeful that if the same effect is seen in humans, a new class of drugs for treating the clinically obese will be developed.
Using X-ray crystallography, the researchers are producing a three dimensional map of the structure of the protein. It was previously known that ZAG was similar in structure to proteins known as major histocompatibility complex (MHC) proteins. These proteins are active in the body's immune system. The 3D mapping surprised researchers in that the structure of ZAG was even more similar to the MHC proteins than researchers had suspected. Interestingly enough, ZAG has no known role in the immune system.
MHC proteins have a large notch that binds a specific type of peptide. In elucidating the structure, the researchers found that ZAG also has the notch but it doesn't bind the same type of peptides as the MHC proteins. At present, the researchers are still attempting to identify the molecule that binds to the ZAG notch. The researchers believe that whatever binds to the notch may fully elucidate the mechanism of how ZAG promotes fat breakdown. They further note that once the molecule is identified, inhibiting its binding to the notch may prove to be a successful treatment to stem fat breakdown.
If scientists are successful, not only could clinical obesity be treated but those suffering from a variety of fat breakdown disorders like cachexia could be successfully treated. Breast cancer patients could also benefit, since ZAG is known to accumulate in more than 40 percent of cancerous tissue in the breast.
What do you think? Will this research lead to a new class of drugs? What are the possibilities for a drug with little to no side effects? Come over to the Biology Forum and share your thoughts, opinions, and feelings. 'Til next time...
For related information, see:
Fat-Fighting Drug
Scientists are on the verge of developing a drug that can control weight gain.
