Navigation Links
Drug dials down the energy within cells, UM researchers find

A drug effective at treating animal models of human autoimmune disorders and other diseases works by dialing down the activity of a key enzyme involved in energy production, University of Michigan researchers have found.

"Many drugs block the function of enzymes, essentially turning them off," said Gary Glick, who is the Werner E. Bachmann Collegiate Professor of Chemistry at U-M. "Our compound works more like a volume control, so we're able to dial enzyme activity down to a level that maintains normal function while simultaneously allowing for initiation of a process that selectively kills or disables disease-causing cells."

Glick and collaborators published their findings in the June 16 issue of ACS Chemical Biology.

The drug, discovered by Glick and coworkers and called benzodiazepine-423 (Bz-423), is a chemical cousin of anti-anxiety medications such as Valium and Xanax. In previous work, Glick's group showed that Bz-423 reduces effects of arthritis and the autoimmune disease lupus in mice and may be useful in treating psoriasis. Unlike conventional drugs for these conditions, which can't discriminate between healthy and disease-causing cells, Bz-423 is highly selective, homing in on disease-causing cells.

In an attempt to better exploit its therapeutic properties, the researchers have been studying the details of Bz-423's activity. They learned that the compound targets an enzyme inside mitochondria, the energy factories of cells. The specific enzyme, F1F0-ATPase, is responsible for producing most of the cell's ATP. That's a critical role because ATP, often referred to as the cell's energy currency, is the molecule that captures chemical energy from food and transfers it to energy-demanding processes, such as muscle contraction and the transmission of nerve signals.

"People had proposed in the past that if you could inhibit this enzyme, there might be therapeutic potential. But the problem is, if you inhibit the enzyme in the way most powerful drugs do, turning it off, you deplete the cell of ATP, and that's fatal," Glick said. "Our new work reveals the mechanism by which Bz-423 inhibits the enzyme while still allowing it to function. This is important because it suggests principles that may be useful for targeting other bioenergetic pathways. Now we have some rules that we can apply to be able to modulate the mitochondria in new ways that could be therapeutic."

Ultimately, the findings may have applications not only for lupus, arthritis and psoriasis, but also for other conditions, Glick believes. "There are other diseases---certain cancers and a number of other immune diseases---where we think the way the cells make and utilize energy is fundamental to the disease process. Combining that knowledge with our new knowledge of how to regulate the energy of the cell could open up new avenues for treating disease and monitoring the effectiveness of treatment."


'"/>

Source:University of Michigan


Related biology news :

1. Growth in biomass could put US on road to energy independence
2. Hydrogen and methane provide raw energy for life at Lost City
3. Study of energy and health in Africa focuses spotlight on charcoal and forest management
4. UCSD study clarifies insulins role in blocking release of energy in patients with type II diabetes
5. Ethanol and biodiesel from crops not worth the energy
6. Free-energy theory borne out in large-scale protein folding
7. Odd energy mechanism in bacteria analyzed
8. Environmental metagenomics diagnosing extreme environments, tapping opportunities for clean energy
9. Lactic acid not athletes poison, but an energy source - if you know how to use it
10. Taking evolutions temperature: Researchers pinpoint the energy it takes to make a species
11. Johns hopkins researchers find link between cells energy use and genome health
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/15/2016)... 2016 Research and Markets has ... Market 2016-2020,"  report to their offering.  , ... ,The global gait biometrics market is expected to ... period 2016-2020. Gait analysis generates multiple ... used to compute factors that are not or ...
(Date:3/31/2016)... , March 31, 2016  Genomics firm Nabsys has ... CEO, Barrett Bready , M.D., who returned to ... the original technical leadership team, including Chief Technology Officer, ... Product Development, Steve Nurnberg and Vice President of Software ... the company. Dr. Bready served as CEO ...
(Date:3/22/2016)... , PROVO and ... Newborn Screening Ontario (NSO), which operates the highest sample ... molecular testing, and Tute Genomics and UNIConnect, leaders in ... respectively, today announced the launch of a project to ... (NGS) testing panel. NSO has been ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... ... 2016 , ... The Ankle Plating System 3 and Small ... fractures of the distal tibia and fibula. This system marks Acumed's continued commitment ... is composed of seven plate families that span the lateral, medial, and posterior ...
(Date:5/25/2016)... ... May 25, 2016 , ... ... (RFI) issued by the Office of the National Coordinator for Health IT (ONC) ... determines if clinically relevant data were available when and where it was needed. ...
(Date:5/25/2016)... CITY, UTAH. (PRWEB) , ... May 25, 2016 , ... ... in healthcare information exchange, today announced that Charles W. Stellar has been named by ... WEDI’s interim CEO since January 2016. As an executive leader with more than 35 ...
(Date:5/25/2016)... ... May 25, 2016 , ... ... Drug Administration (FDA) has granted the company’s orphan drug designation request covering BHV-4157 ... drug designation granted by the FDA. , Spinocerebellar ataxia is a rare, ...
Breaking Biology Technology: