Additional
regulation of MMP activity is accomplished by the presence of
endogenous MMP inhibitors, such as 2-macroglobulin and the
TIMPs. There are four human TIMPs, all of which are lowmolecular-
weight secreted proteins that bind non-covalently to
the active site of MMPs in a 1:1 ratio. MMP activity is thus
tightly regulated in normal physiological processes, but when
one or more of these regulatory controls are by-passed,
excessive degradation and tissue destruction may occur.