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, including saliva, sweat, urine, and blood.
During the last year, researchers discovered that ZAG was involved in a wasting syndrome, known as cachexia, most often associated with terminal illness such as AIDS or cancer. Cachexia leads to rapid weight 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. When it was fed to rats, they lost weight even though their caloric consumption remained the same. 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, scientists are producing a three-dimensional map of the structure of the protein. It was already known that ZAG was similar in structure to proteins known as major histocompatibility complex (MHC), the proteins 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 previously 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, researchers are still attempting to identify the molecule that binds to the ZAG notch. They believe that whatever binds to the notch will clearly show how ZAG promotes fat breakdown. They further note that once the molecule is identified, inhibiting its binding to the notch may successfully stem fat breakdown.
If scientists are successful, not only could the clinically obese be treated, but also those suffering from 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 or 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.
