Human plasma apolipoprotein (apo) A-I has been shown to be synthesized as a preproapolipoprotein. ProapoA-I undergoes post-translational proteolytic processing to mature apoA-I. In addition, apoA-I has been shown to undergo post-translational acylation with fatty acids. The biosynthesis and processing of apoA-I involves several different types of processing including proteolysis as well as modification with different prosthetic groups. The processing of apolipoproteins may play an important role in the metabolism as well as physiological function of the plasma apolipoproteins and lipoproteins. The complete covalent structure of apoC-III has been determined in normal subjects. This structure differed from that previously determined from a patient with type V hyperlipoproteinemia. These results suggests that structural variants of apolipoproteins may be present which are importnt in the pathophysiology of the human dyslipoproteinemias. Two different isoforms of apoA-I have been isolated from Tangier patients. One form of apoA-I was electrophoretically as well as kinetically similar to normal apoA-I. The other isoform had an apparent molecular weight which was 2000 daltons less than normal apoA-I, and was rapidly catabolized when injected into normal controls. These results indicate that the defect in Tangier disease is due to an abnormality in post-translational processing of apoA-leading to reduced levels of HDL. ApoB-100 has been cloned in an Lambdagt-11 expression vector. The expressed fusion protein contains a 60,000 dalton apoB-100 protein which reacted with a monoclonal antibody that is specific for the LDL receptor binding site. The cloned apoB-100 contains the LDL receptor binding domain, and will permit detailed studies on the interaction of apoB-100 and the LDL receptor.
