Unstable enzyme underlies inherited ALS.
In March, researchers announced they had pinpointed the faulty gene in the familial form of amyotrophic lateral sclerosis amyotrophic lateral sclerosis (ALS) (ā'mīətrōf`ik, sklĭrō`sĭs) or motor neuron disease, (ALS Als (äls), Ger. Alsen, island, 121 sq mi (313 sq km), Sønderjylland co., S Denmark, in the Lille Bælt, separated from the mainland by the narrow Alensund. ), often called Lou Gehrig's disease Lou Geh·rig's disease
See amyotrophic lateral sclerosis. (SN: 3/6/93, p. 148). Mistakes in that gene's sequence lead to alterations in an enzyme called superoxide dismutase. Typically, this enzyme becomes active when two identical "subunits" link up (as shown) to form a "dimer dimer /di·mer/ (di´mer)
1. a compound formed by combination of two identical molecules.
2. a capsomer having two structural subunits.
1. " and disarm potentially harmful oxygen free radicals by converting them to hydrogen peroxide or molecular oxygen.
Using X-ray crystallography and computer graphics techniques, John A. Tainer and his colleagues at the Scripps Research Institute in La Jolla, Calif., found that enzyme alterations (the most common in red; others, in gold) do not affect the sites (orange and blue) where this chemical conversion occurs. Instead the alterations weaken the dimer linkage, causing it to fall apart easily. Thus the enzyme scavenges fewer free radicals, says Teepu Siddique of Northwestern University Medical School in Chicago.
He and his colleagues measured the enzyme's activity in the red blood cells Red blood cells
Cells that carry hemoglobin (the molecule that transports oxygen) and help remove wastes from tissues throughout the body.
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red blood cells of 15 ALS patients from seven families inherited ALS. The enzyme worked between one-third and one-half as well as normal, they and collaborators from several institutions, including Scripps, report in the Aug. 20 SCIENCE.
"Now we know this disease is caused by free radicals," Siddique says. These results strongly suggest that therapy involving this enzyme or some surrogate compound (not simple antioxidants Antioxidants
Substances that reduce the damage of the highly reactive free radicals that are the byproducts of the cells.
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n. such as vitamins) may help slow both the inherited and noninherited forms of the illness.