1. An
enzyme system present in a rat liver lysosome-rich fraction was found to liberate soluble
hydroxyproline-containing products from insoluble
collagen, with maximum activity at pH3.45. It was concluded that a form of
cathepsin D was involved since synthetic substrates specific for
trypsin were not hydrolysed. Collagenolysis was enhanced by
thiol compounds and inhibited by Cu(2+)
ions and the anti-inflammatory drugs
phenylbutazone and
ibufenac. 2. The possibility that behaviour of
collagen and collagenolysis were modified by various substances, either by destruction of intramolecular and intermolecular bonds in
tropocollagen or by electrostatic interactions, is discussed. Insoluble
collagen was found to bind electrostatically to chondromucoprotein. This interaction was inhibited by some anti-inflammatory drugs. 3. Possible roles of the lysosomal collagenolytic
enzyme system in experimental
lathyrism in rats given
penicillamine, and in erosion of cartilage in
rheumatoid arthritis, are considered. 4. Collagenolysis in vivo, which may depend on complex interrelationships between
collagen, chondromucoprotein and
metal ions, is discussed in relation to possible effects, both harmful and beneficial, of anti-inflammatory drugs used in
rheumatoid arthritis.