Enkephalinase

Enkephalinase

Enkephalinase is an enzyme that plays a crucial role in the metabolism of enkephalins, which are endogenous opioid peptides involved in regulating pain and emotion. Enkephalinase is also known as neutral endopeptidase (NEP) or CD10.

Function

Enkephalinase is a zinc-dependent metalloendopeptidase that cleaves peptide bonds on the amino side of hydrophobic residues. It is primarily responsible for the degradation of enkephalins, which are neurotransmitters that bind to opioid receptors in the central nervous system and peripheral nervous system. By breaking down enkephalins, enkephalinase regulates their activity and duration of action.

Structure

Enkephalinase is a membrane-bound enzyme that is anchored to the cell membrane via a single transmembrane domain. The active site of the enzyme contains a zinc ion, which is essential for its catalytic activity. The enzyme is composed of several domains, including a large extracellular domain where substrate binding and catalysis occur.

Biological Role

Enkephalinase is widely distributed in various tissues, including the brain, kidneys, and lungs. In the brain, it modulates the activity of enkephalins, thereby influencing pain perception, mood, and stress response. In the kidneys, enkephalinase is involved in the regulation of blood pressure and sodium balance.

Clinical Significance

Inhibition of enkephalinase has been explored as a therapeutic strategy for enhancing the effects of enkephalins, particularly in the management of pain and depression. Enkephalinase inhibitors, such as racecadotril, are used to treat diarrhea by reducing the breakdown of enkephalins in the gastrointestinal tract, thereby decreasing intestinal secretion.

Research and Development

Ongoing research is focused on developing selective enkephalinase inhibitors that can be used to treat various conditions, including chronic pain, hypertension, and heart failure. Understanding the structure and function of enkephalinase is crucial for the design of these inhibitors.

See Also

• Opioid receptor
• Endorphin
• Neurotransmitter
• Metalloendopeptidase