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Steps to Block Key Enzyme Action in Heart Failure Mapped

by VR Sreeraman on November 13, 2008 at 5:19 PM
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 Steps to Block Key Enzyme Action in Heart Failure Mapped

In a breakthrough study, scientists at Johns Hopkins have mapped out a key chemical step involved in blocking enzyme action in heart failure.

The team showed how the enzyme, phosphodiesterase 5, or PDE5A, involved in heart failure, slows down the breakdown of another vital compound called, cyclic guanosine monophosphate (cyclic GMP), which is critical to cell growth and muscle contraction.

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They identified a sulfur- and nitrogen-containing molecule, or S-nitrosyl group that chemically alters the enzyme's amino-acid building blocks.

This so-called S-nitrosylation of amino acid cysteine 181 lead to a 25 percent reduction in PDE5A activity, pinpointing how the enzyme's action is suppressed.
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"Knowing the molecular make-up and activity of a protein is critical to understanding heart failure because these problem-specific biochemical reactions are magnified in the disease," said senior study investigator Jennifer Van Eyk, Ph.D., a professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute.

"Targeted drug therapies can now be developed and tested to work specifically on cysteine 181, to block the PDE5A enzyme, lower the breakdown of cyclic GMP, and potentially stall progression of heart failure and hypertrophy," she added.

The researchers said that their next step is to investigate how PDE5A affects where cyclic GMP is broken down or made, with the goal of determining if the enzyme also controls the known cell pooling of the compound.

The study was presented at the American Heart Association's annual Scientific Sessions in New Orleans.

Source: ANI
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