IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2012;4(1):10-27.

Review Article
Gastrointestinal absorption and biological activities of serine and cysteine
proteases of animal and plant origin: review on absorption of serine and cysteine
proteases

Gerhard Lorkowski

GL Pharma Consulting Research & Development (GL Pharma CR&D), Microbiology of the University of Muenster, D-82131
Gauting/Munich, Germany

Received December 19, 2011; accepted February 12, 2012; Epub February 28, 2012; Published March 15, 2012

Abstract: Research has confirmed that peptides and larger protein molecules pass through the mucosal barrier of the gastrointestinal
tract. Orally administered serine and cysteine proteases of plant and animal origin also reach blood and lymph as intact, high
molecular weight and physiologically active protein molecules. Their absorption may be supported by a self-enhanced paracellular
transport mechanism resulting in sub-nanomolar concentration of transiently free protease molecules or, in a complex with
anti-proteases, at higher concentrations. Data from pharmacokinetic investigations reveals dose linearity for maximum plasma levels
of free proteases not unusual for body proteases and a high inter-individual variability. There is no interference with each other after oral
administration of combinations and absorption follows an unusual invasion and elimination kinetic due to slow velocity of absorption
and a fast 100% protein binding to anti-proteases. Oral application of proteases leads to increased proteolytic serum activity and
increased plasma concentrations of the corresponding anti-proteases. Their biological activity is determined by their proteolytic activity
as free proteases on soluble peptides/proteins or cell surface receptors (e.g. protease activated receptors) and their activity in the
complex formed with their specific and/or unspecific anti-proteases. The anti-protease-complexes, during immune reaction and
injuries often loaded with different cytokines are cleared from body fluids and tissue by receptor mediated endocytosis on hepatocytes
and/or blood cells. Oral administration of enteric coated tablets containing proteolytic enzymes of plant and animal origin may be a safe
method to stabilize, positively influence or enhance physiological and immunological processes during disease processes or in
healthy consumers. (IJPPP1112001).

Keywords: Gastrointestinal absorption, serine and cysteine protease, proteinase, proteolytic enzyme activity, anti-protease, protease
activated receptors


Address all correspondence to:
Dr. Gerhard Lorkowski
GL Pharma Consulting Research & Development (GL Pharma CR&D)
Hubertusstr. 77a, D-82131 Gauting, Germany.
Tel: +49-89-803696; Fax: +49-89-803644
Phone: +49-171-641 99 75; E-mail: gerhard.lorkowski@gmx.de