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Enkephalinase: selective inhibitors and partial characterization.

S Sullivan, H Akil, D Blacker

    Peptides
    |January 1, 1980
    PubMed
    Summary
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    Brain enzymes metabolize enkephalins. Researchers identified enkephalinase (an endopeptidase) as specific to the endogenous enkephalinergic system, with distinct inhibitors found for it and aminopeptidases.

    Area of Science:

    • Neurochemistry
    • Enzymology
    • Pharmacology

    Background:

    • Enkephalins are endogenous neuropeptides involved in pain modulation and other neurological functions.
    • Enkephalin metabolism in the brain is primarily carried out by two enzyme classes: endopeptidases and aminopeptidases.

    Purpose of the Study:

    • To characterize enzymes that metabolize enkephalins in the brain.
    • To identify specific inhibitors for different classes of enkephalin-metabolizing enzymes.
    • To investigate the properties of enkephalinase and compare it with other enzymes like angiotensin-converting enzyme.

    Main Methods:

    • Enzyme activity assays were performed to study enkephalin metabolism.
    • Selective inhibitors were synthesized and tested against endopeptidases and aminopeptidases.

    Related Experiment Videos

  • Enzyme characteristics such as buffer dependence, chloride dependence, and inhibitor susceptibility were evaluated.
  • Main Results:

    • Enkephalinase, an endopeptidase cleaving the Gly-Phe bond, was identified as specific to the endogenous enkephalinergic system.
    • Selective inhibitors were found: parachloromercuriphenylsulfonic acid and puromycin for aminopeptidases, and enkephalin fragments for enkephalinase.
    • Enkephalinase shares properties with angiotensin-converting enzyme but differs in chloride dependence, buffer activity, and inhibitor susceptibility.

    Conclusions:

    • Enkephalinase is a key enzyme in the endogenous enkephalinergic system.
    • Distinct inhibitors can selectively target different enkephalin-metabolizing enzymes.
    • Enkephalinase exhibits unique properties differentiating it from angiotensin-converting enzyme, despite some shared characteristics.