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Dec 7, 2007

Researchers Identify Protein that Prevents Toxic Build-Up of Otherwise Naturally Occuring Compound

  • Scientists say that a transporter protein known as PEPT2 protects the brains of mice from a naturally occurring but potentially toxic compound.

    The research team dosed mice with 5-aminolevulinic acid (5-ALA). This compound, which occurs naturally in the body, is involved in forming a substance called heme, which is a component of hemoglobin as well as many important enzymes.

    If there is an accumulation or an overproduction of 5-ALA in the body, however, it can become toxic. High concentrations of 5-ALA are present in people who have lead poisoning or hepatic porphyrias.

    The team found that when dosed with 5-ALA, mice without PEPT2 died sooner, had neuromuscular dysfunction, and had up to 30 times higher concentrations of the toxic compound in their cerebrospinal fluid than did mice with PEPT2.

    “The findings suggest that the PEPT2 protein could work the same way in humans,” according to David Smith, coauthor of the paper and the University of Michigan professor and chair of pharmaceutical sciences. “If that is the case, then PEPT2 may have relevance as a secondary genetic modifier of conditions such as acute hepatic porphyrias and lead poisoning and in drug transport at the blood-brain barrier.

    The paper is published in the December issue of the Journal of Neurochemistry.



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