Structure and function of human low density lipoproteins. Studies using proteolytic cleavage by plasma kallikrein.

Kallikrein digestion of human low density lipoproteins (LDL) has recently been shown to result in the degradation of apolipoprotein B (apo-B) into four major fragments, two of them being B-26 and B-74, which have been reported to be present in the LDL of some individuals. We studied the binding of kallikrein-treated LDL to human fibroblasts; digestion did not affect binding. Digested LDL was not taken up by macrophages, showing that it behaved like normal LDL. The activation of acyl-CoA cholesterol acyltransferase by LDL in fibroblasts was also not altered by kallikrein digestion. When delipidated LDL was treated with kallikrein, apo-B was digested into very small fragments, indicating that kallikrein can cleave apo-B at sites other than those which result in the formation of B-26 and B-74. The partial delipidation of LDL with heptane also resulted in more extensive digestion of apo-B, although binding to cells was unaffected. These studies suggest that the cholesterol core maintains the proper orientation of apo-B in the LDL particle and that kallikrein may be used as a tool to elucidate the association of apo-B and lipids in the LDL particle.