Lysyl oxidase catalyzes the oxidation of peptidyllysine to o-arninoadipic-d-semialdehyde, the precursor to the covalent crosslinkages that stabilize fibers of elastin and collagen. This enzyme contains both copper and a carbonyl cofactor consistent with an o-quinone. The proposed mechanism of action is derived from available kinetic and chemical data and also can account for mechanism-based inhibition of the enzyme by specific monoamines and diamines. Recent evidence for biosynthetic precursors and for the. regulation of lysyl oxidase in fibrotic and malignant diseases is discussed.

Elastin and collagen are examples of proteins whose formation and maturation are critically dependent upon post-translational modifications. Thus, collagen is post-translationally processed by several different catalysts to cleave signal peptides, hydroxylate proline and lysine residues, glycosylate hydroxylysines, cleave register peptides, and oxidize lysine residues. The latter modification, catalyzed by lysyl oxidase (EC 1.4. 3.13), generates peptidyl o-aminoadipic-e-semialdehyde in collagen as well as elastin. The aldehyde residue can spontaneously condense with neighboring aldehydes or e-amino groups to form interchain or intrachain covalent crosslinkages, two of which are shown (Figure 1). Continuous, intermolecular condensations of this kind will then convert soluble monomers of elastin or collagen into insoluble fibers in the extracellular matrix. Thus, lysyl oxidase can potentially regulate the development and repair of the matrix in lung and other connective tissues. The present review will summarize findings appearing since a previous detailed review on the properties and regulation of this catalyst (1).