This paper is only available as a PDF. To read, Please Download here.
An extract of porcine brain acetone powder incubated with thyrotropin-releasing hormone (TRH; pGlu-His-ProNH2) produces acid TRH (pGlu-His-Pro), histidine, and prolineamide. Fractionation of the brain extract by DEAE-cellulose chromatography produces three protein fractions which metabolize TRH. The activity of these fractions was characterized using TRH with a 3H-label on the histidine or proline as well as [His-3H]His-ProNH2. Fraction I contains pyroglutamate aminopeptidase and Fraction II contains TRH deamidase. Fraction III was found to contain a previously unrecognized enzyme which cleaves His-ProNH2 to histidine and proline. The histidylprolineamide imidopeptidase has been characterized. A competition study using a variety of compounds containing histidine or proline suggests that the best substrates for the imidopeptidase contain a free alpha-amino group on histidine and a blocked carboxyl group on proline, as is found in His-ProNH2. A survey of a variety of polypeptide hormones indicates that many of them inhibit the imidopeptidase activity. A kinetic study of the inhibition of the enzyme by adrenocorticotropic hormone (1-24) shows that the inhibition by polypeptide hormones is noncompetitive. We hypothesize that pituitary hormones may stimulate the production of (cyclo)-His-Pro by inhibiting alternate routes of TRH metabolism.
REFERENCES
- Annu. Rev. Physiol. 1976; 38: 389-424
- Hormones. 1971; 2: 193-203
- Biochemistry. 1971; 10: 3621-3624
- Neuroendocrinology. 1975; 19: 277-287
- J. Biol. Chem. 1976; 251: 3229-3234
- Nature. 1977; 268: 142-144
- Biochim. Biophys. Acta. 1976; 444: 428-434
- Biochem. Biophys. Res. Commun. 1976; 73: 507-515
- Lipmann Symposium: Energy, Biosynthesis and Regulation in Molecular Biology. Walter de Gruyter, New York1974: 53-62
- Endocrinology. 1976; 99: 230-242
- Anal. Biochem. 1976; 76: 125-133
- Dawson R.M.C. Elliott D.C. Elliott W.H. Jones K.M. Data For Biochemical Research. Oxford University Press, London1959: 229
- Enzyme Kinetics. John Wiley and Sons, New York1975: 132
- Ganong W.F. Martini L. Frontiers in Neuroendocrinology. Oxford University Press, New York1973: 375-413
- J. Neurochem. 1978; 30: 321-327
- Methods Enzymol. 1970; 19: 521-534
- Clin. Endocrinol. Metab. 1977; 6: 83-100
Article info
Publication history
Published online: April 10, 1979
Identification
Copyright
© 1979 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.
User license
Creative Commons Attribution (CC BY 4.0) | How you can reuse 
Elsevier's open access license policy
Creative Commons Attribution (CC BY 4.0)
Permitted
- Read, print & download
- Redistribute or republish the final article
- Text & data mine
- Translate the article
- Reuse portions or extracts from the article in other works
- Sell or re-use for commercial purposes
Elsevier's open access license policy
