Lysyl oxidase: mechanism, regulation and relationship to liver fibrosis

Abstract

Lysyl oxidase oxidizes peptidyl lysine in collagen and elastin substrates to residues of alpha-aminoadipic-delta-semialdehyde. The peptidyl aldehydes can then undergo spontaneous condensations with unreacted epsilon-amino groups and with neighboring aldehyde functions, thus forming the covalent crosslinkages which convert elastin and collagen into insoluble fibers. The unique role of lysyl oxidase in the post-translational modification of these proteins qualifies this enzymatic reaction as a potentially pivotal site of biological and/or chemotherapeutic control of collagen fiber deposition. Recent advances in the study of the catalytic mechanism, in the development of active site inhibitors, and in the biosynthesis and regulation of this unusual catalyst are reviewed as are studies on the response of lysyl oxidase in fibrotic liver.