Pyroglutamyl peptidase: an overview of the three known enzymatic forms

Pyroglutamyl peptidase can be classified as an omega peptidase which hydrol ytically removes the amino terminal pyroglutamate (pGlu) residue from speci fic pyroglutamyl substrates. To date, three distinct forms of this enzyme h ave been identified in mammalian tissues. Type I is typically a cytosolic, cysteine peptidase displaying a broad pyroglutamyl substrate specificity an d low molecular mass. Type II has been shown to be a membrane anchored meta lloenzyme of high molecular mass with a narrow substrate specificity restri cted to the hypothalamic releasing factor, thyrotropin-releasing hormone (T RH, pGlu-His-Pro-NH2). A third pyroglutamyl peptidase activity has also bee n observed in mammalian serum which displays biochemical characteristics re markably similar to those of tissue Type II, namely a high molecular mass, sensitivity to metal chelating agents, and a narrow substrate specificity a lso restricted to TRH. This serum activity has subsequently been designated 'thyroliberinase'. This review surveys the biochemical, enzymatic, and str uctural properties of this interesting and unique class of peptidases. It a lso addresses the putative physiological roles which have been ascribed to these enzymes. Pyroglutamyl peptidase activities isolated and characterized from bacterial sources are also reviewed and compared with their mammalian counterparts. (C) 1998 Elsevier Science B.V. All rights reserved.