Histidyl-proline diketopiperazine. Novel formation that does not originate from thyrotropin-releasing hormone.
We asked whether cyclo(His-Pro) may arise from a substance other than the initially found progenitor thyrotropin-releasing hormone (TRH). Incubation of TRH-Gly (pGlu-His-Pro-Gly), a TRH precursor, with brain hypothalamic cytosols caused significant formation of His-Pro-Gly followed by the generation of histidyl-proline diketopiperazine (cyclo(His-Pro)), whereas TRH was not formed. The addition of purified pyroglutamyl 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 under the present conditions. Nonenzymatic conversion of His-Pro-Gly to cyclo(His-Pro) occurred. The present results provide evidence that cyclo(His-Pro) can emanate from a direct predecessor form of TRH by pyroglutamyl aminopeptidase action, not through TRH formation.
Miyashita
K
K
First Department of Internal Medicine, Gunma University, School of Medicine, Maebashi, Japan.
Murakami
M
M
Yamada
M
M
Iriuchijima
T
T
Mori
M
M
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D010456:Peptides, Cyclic; D010879:Piperazines; D013973:Thyrotropin-Releasing Hormone; D000626:Aminopeptidases; C015924:histidyl-proline diketopiperazine