Apetulant, wild enzyme blamed for triggering a host of killer diseases from type 2 diabetes, arthritis, hypertension and to an extent, even cancer, and whose working has foxed international researchers may have been finally tamed at the Indian Institute of Science (IISc), Bangalore.
Type 2 diabetes is a medical condition in which the body produces too little insulin, a chemical responsible for the absorption of sugar into cells from the bloodstream. One of the lead villains responsible for this condition is an enzyme called phosphotyrosine phosphatase 1B (PTP 1B) that produces a class of substances called sulfenyl-amides, which when activated derail the insulin production process.
“That’s unusual behaviour, because PTP 1B is a protein and proteins never produce sulfenyl-amides,” said Gary Truett of the University of Tennessee and an expert on diabetes research in an email interview. Not only was such a phenomenon—discovered and reported in Nature in 2003— perplexing, nobody could figure out how it happened.
Enzymes behave like switches, and usually triggering one of them sets off other related ones. So, a typical approach to developing a drug is turning off a major offending enzyme, and in this case of diabetes type 2, turning off PTP 1B involves preventing the sulfenyl-amides from getting activated.
“Most treatment approaches for diabetes type 2 involve direct targeting of the enzyme in question,” said G. Mugesh, assistant professor, department of inorganic and physical chemistry, IISc, adding that such an approach affects other enzymes, causing side effects.
So Mugesh decided to focus on the sulfenyl-amides instead, says an article in the July issue of the peer-reviewed Journal of the American Chemical Society. Mugesh and his graduate student, Bani Kanta Sarma, “bio-mimicked” PTP 1B, meaning they prepared a compound simulating the region on an enzyme where all the chemical activity takes place and recreated the process of formation of sulfenyl-amides in the laboratory.
“This approach has implications for drug therapy,” said Mugesh. Drug makers are bound to be interested, as diabetes accounts for a large part of R&D expenditure, with researcher Medco Health Solutions estimating it at $8.4 billion (Rs33,348 crore) just in the US. India, says the World Health Organization, has 30 million diabetics, 90% of them ailing from the type 2 variant.
“It is certainly an interesting approach,” said Kanta Sharma, a nutritionist at the Sir Gangaram Hospital here. “Giventhat current diabetic medication also brings in risks of heart failure, rigid diet plans and even risks of kidney failure, a new approach mightbe popular.”