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Kinetics of the Interaction of Human Leucocyte Elastase with Protein Substrates: Implications for Enzyme Inhibition

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Biochemistry of Pulmonary Emphysema

Part of the book series: Current Topics in Rehabilitation ((CURRENT REHAB))

Abstract

Human leucocyte elastase (EC 3.4.21.37) is possibly one of the most destructive enzymes in the body, having the ability to degrade many components of the extracellular matrix such as insoluble collagens type I and II,1 type III collagen,2 type IV collagen,3,4 proteoglycans1,5 and elastin.6,7 Other natural substrates degraded by leucocyte elastase are the four human immunoglobulin G subclasses,8 immunoglobulin M9 and the cell adhesion molecule fibronectin.10 For these reasons leucocyte elastase has been associated with pathological states characterized by an abnormal degradation of connective tissue, in particular with pulmonary emphysema,11,12 rheumatoid arthritis,13 clotting disorders and other inflammatory processes.14 An attractive approach for the treatment of emphysema15–17 and other pathological states characterized by the loss of the structural elements of the extracellular matrix is the use of low molecular mass synthetic inhibitors of endopeptidases. However, despite the existence of a large number of endopeptidase inhibitors that are very active in vitro, very few of them are able to exert beneficial effects in vivo through inhibition of proteolysis. The manifold reasons for this failure, which are essentially due to the particular nature of the enzymes and their target substrates in the extracellular matrix, such as collagen, proteoglycans and elastin, have been discussed.18

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Authors and Affiliations

  1. Department of Rheumatology, University Hospital, Zurich, Switzerland

    A. Baici

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  1. A. Baici
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Editors and Affiliations

  1. Institute of Phthisiology and Respiratory Diseases, IRCCS San Matteo, University of Pavia, Italy

    C. Grassi  & M. Luisetti  & 

  2. Department of Biochemistry, University of Georgia, Athens, GA, USA

    J. Travis

  3. Postgraduate School of Respiratory Diseases, University of Pavia, Italy

    L. Casali

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© 1992 Springer-Verlag London

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Baici, A. (1992). Kinetics of the Interaction of Human Leucocyte Elastase with Protein Substrates: Implications for Enzyme Inhibition. In: Grassi, C., Travis, J., Casali, L., Luisetti, M. (eds) Biochemistry of Pulmonary Emphysema. Current Topics in Rehabilitation. Springer, London. https://doi.org/10.1007/978-1-4471-3771-9_7

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  • DOI: https://doi.org/10.1007/978-1-4471-3771-9_7

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-3773-3

  • Online ISBN: 978-1-4471-3771-9

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