K. Miyashita et al., HISTIDYL-PROLINE DIKETOPIPERAZINE - NOVEL FORMATION THAT DOES NOT ORIGINATE FROM THYROTROPIN-RELEASING-HORMONE, The Journal of biological chemistry, 268(28), 1993, pp. 20863-20865
We asked whether cyclo(His-Pro) may arise from a substance other than
the initially found progenitor thyrotropin-releasing hormone (TRH). In
cubation of TRH-Gly (pGlu-His-Pro-Gly), a TRH precursor, with brain hy
pothalamic cytosols caused significant formation of His-Pro-Gly follow
ed by the generation of histidyl-proline diketopiperazine (cyclo(His-P
ro)), whereas TRH was not formed. The addition of purified pyroglutamy
l aminopeptidase resulted in the transformation of TRH-Gly to His-Pro-
Gly and cyclo(His-Pro) but not to TRH. Neither TRH nor cyclo(His-Pro)
was produced from TRH-Gly in the presence of alpha-amidating enzyme un
der the present conditions. Nonenzymatic conversion of His-Pro-Gly to
cyclo(His-Pro) occurred. The present results provide evidence that cyc
lo(His-Pro) can emanate from a direct predecessor form of TRH by pyrog
lutamyl aminopeptidase action, not through TRH formation.