Metabolism of thyrotropin releasing hormone in brain extracts. isolation and characterization of an imidopeptidase for histidylprolineamide

Date
1979
Authors
Matsui, T.
Prasad, C.
Peterkofsky, A.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract

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.

Description
Article originally published in Journal of Biological Chemistry, 254(7), 2439–2445. English. Published Online 2021. https://doi.org/10.1016/s0021-9258(17)30242-9
Keywords
Adrenocorticotropic hormone, Polypeptide hormones, Imidopeptidase activity
Citation
This is the published version of an article that is available at https://doi.org/10.1016/s0021-9258(17)30242-9. Recommended citation: Matsui, T., Prasad, C., & Peterkofsky, A. (1979). Metabolism of thyrotropin releasing hormone in brain extracts. isolation and characterization of an imidopeptidase for histidylprolineamide. Journal of Biological Chemistry, 254(7), 2439–2445. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.