TY - JOUR
T1 - Cleavage of endorphins to des-tyr endorphins by homogeneous bovine brain aminopeptidase
AU - Hersh, Louis B.
AU - Smith, Thomas E.
AU - McKelvy, Jeffrey F.
PY - 1980
Y1 - 1980
N2 - Attention has recently focused on the possible biological roles of peptides related to β-1ipotropin (β-LPH)1,2. In particular, observations suggest that certain peptide fragments derivable from β-LPH, including γ-endorphin (β-LPH61-77) and α-endorphin (β-LPH61-76), may be involved in various modes of behavioural adaptation2,3. Structure-activity studies on behavioural actions of γ-endorphin, an opioid peptide, revealed that the omission of N-terminal tyrosine resulted in a non-opioid peptide, des-Tyr-γ-endorphin, which exhibited greater behavioural activity than γ-endorphin3. Subsequent biochemical studies provided evidence for the association with brain synaptic plasma membranes of peptidase activities which could produce γ- and α-endorphins and their des-Tyr derivatives from exogenous β -endorphin4. This and earlier observations4ndash;6 suggest that regulatory physiological events are focused on the N-terminal tyrosine residue; enzymatic reactions exerted at this residue are thus of great interest. We recently purified to homogeneity an aminopeptidase from bovine brain which catalyses the hydrolysis of Met5- or Leu5-enkephalin by sequential release of amino acids from the amino terminus of the enkephalin molecule7. The ability of this enzyme, purified from bovine7, monkey8 or rat9 brain, to use endorphins as substrates has not been previously examined. We now present quantitative studies which show that homogeneous bovine brain enkephalin aminopeptidase catalyses the hydrolysis of the N-terminal tyrosine from γ-, α- and β -endorphins with substantial turnover numbers and yields only the des-Tyr derivatives. These results suggest that this enzyme may be involved in regulating the concentrations of opioid- and opioid-derived biologically active peptides in the brain.
AB - Attention has recently focused on the possible biological roles of peptides related to β-1ipotropin (β-LPH)1,2. In particular, observations suggest that certain peptide fragments derivable from β-LPH, including γ-endorphin (β-LPH61-77) and α-endorphin (β-LPH61-76), may be involved in various modes of behavioural adaptation2,3. Structure-activity studies on behavioural actions of γ-endorphin, an opioid peptide, revealed that the omission of N-terminal tyrosine resulted in a non-opioid peptide, des-Tyr-γ-endorphin, which exhibited greater behavioural activity than γ-endorphin3. Subsequent biochemical studies provided evidence for the association with brain synaptic plasma membranes of peptidase activities which could produce γ- and α-endorphins and their des-Tyr derivatives from exogenous β -endorphin4. This and earlier observations4ndash;6 suggest that regulatory physiological events are focused on the N-terminal tyrosine residue; enzymatic reactions exerted at this residue are thus of great interest. We recently purified to homogeneity an aminopeptidase from bovine brain which catalyses the hydrolysis of Met5- or Leu5-enkephalin by sequential release of amino acids from the amino terminus of the enkephalin molecule7. The ability of this enzyme, purified from bovine7, monkey8 or rat9 brain, to use endorphins as substrates has not been previously examined. We now present quantitative studies which show that homogeneous bovine brain enkephalin aminopeptidase catalyses the hydrolysis of the N-terminal tyrosine from γ-, α- and β -endorphins with substantial turnover numbers and yields only the des-Tyr derivatives. These results suggest that this enzyme may be involved in regulating the concentrations of opioid- and opioid-derived biologically active peptides in the brain.
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U2 - 10.1038/286160a0
DO - 10.1038/286160a0
M3 - Article
C2 - 7402309
AN - SCOPUS:0019313828
SN - 0028-0836
VL - 286
SP - 160
EP - 162
JO - Nature
JF - Nature
IS - 5769
ER -