PMID: 2118634Jul 1, 1990Paper

Kinetics and pattern of degradation of thyrotropin-releasing hormone (TRH) in human plasma

Pharmaceutical Research
J Møss, H Bundgaard

Abstract

The kinetics and mechanism of degradation of the tripeptide TRH (pGlu-His-Pro-NH2) and its various primary and secondary degradation products (TRH-OH, His-Pro-NH2, and His-Pro) have been determined in human plasma at 37 degrees C. The rates of degradation of both TRH and TRH-OH (pGlu-His-Pro) showed mixed zero-order and first-order kinetics. At low substrate concentrations first-order kinetics occurred, with TRH and TRH-OH degradation half-lives of 9.4 and 27 min, respectively. The initial step in the plasma-catalyzed degradation of TRH is due to hydrolysis of the pGlu-His bond by the TRH-specific pyroglutamyl aminopeptidase serum enzyme, resulting in the exclusive formation of histidyl-proline amide (His-Pro-NH2). Using specific HPLC methods the major degradation route (67%) of this dipeptide in human plasma was hydrolysis of the peptide bond to yield His and Pro-NH2, whereas deamidation to yield His-Pro accounted for 29% of the total degradation. A minor pathway (less than or equal to 4%) was spontaneous cyclization to yield cyclo(His-Pro). Both His-Pro-NH2 and His-Pro degraded by first-order kinetics and faster than TRH, with half-lives of 5.3 and 2.2 min, respectively, in 80% plasma.

Citations

Feb 17, 2009·Nucleosides, Nucleotides & Nucleic Acids·Palaniappan SenthilkumarDharmarajan Sriram
Mar 22, 2007·Journal of Enzyme Inhibition and Medicinal Chemistry·Dhrmarajan SriramPurna Nagashree Kurre
Sep 1, 1992·The Journal of Pharmacy and Pharmacology·K YamadaS Muranishi
Nov 1, 1992·Pharmacology, Biochemistry, and Behavior·W A BanksJ B Jaspan
Aug 4, 2005·Journal of Agricultural and Food Chemistry·Koji IwaiKozo Ohtsuki

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