Lysyl oxidase (LO) is a copper-dependent amine oxidase that plays a critical role
in the biogenesis of connective tissue matrices by crosslinking the extracellular
matrix proteins, collagen and elastin. Levels of LO increase in many fibrotic diseases,
while expression of the enzyme is decreased in certain diseases involving impaired
copper metabolism. While the three-dimensional structure of the enzyme is not yet
available, many of its physical-chemical properties, its novel carbonyl cofactor,
and its catalytic mechanism have been described. Lysyl oxidase is synthesized as a
preproprotein, secreted as a 50 kDa, N-glycosylated proenzyme and then proteolytically
cleaved to the 32 kDa, catalytically active, mature enzyme. Within the past decade,
the gene encoding LO has been cloned, facilitating investigations of the regulation
of expression of the enzyme in response to diverse stimuli and in numerous disease
states. Transforming growth factor-beta, platelet-derived growth factor, angiotensin
II, retinoic acid, fibroblast growth factor, altered serum conditions, and shear stress
are among the effectors or conditions that regulate LO expression. New, LO-like genes
have also been identified and cloned, suggesting the existence of a multigene family.
It has also become increasingly evident that LO may have other important biological
functions in addition to its role in the crosslinking of elastin and collagen in the
extracellular matrix.