The broad objectives of this research plan are to establish structural bases of serum lipoprotein function. We plan to obtain biophysical and chemical information on the organization of the lipid and protein moieties in serum lipoproteins, as well as on enzymatic processes involved in their organization and degradation. The effect of enzymatic processes, particularly those involving lecithin: cholesterol acyltransferase, on lipoprotein structure will be further investigated with model substrates, containing well-defined lipid-protein mixtures. Structural and chemical factors affecting lipoprotein reactivity with enzymes (mainly lecithin: cholesterol acyltransferase) will be evaluated. The physical changes in lipoprotein organization during enzymatic alteration will be probed by methods including analytic ultracentrifugation, electron microscopy, and electron spin resonance (utilizing nitroxide-labeled lipids). Changes in lipoprotein organization during physical-chemical perturbation (including dehydration, heating and solvent exposure) will also be further investigated by these techniques. Transfers of lipoprotein components, to other lipoprotein and/or membraneous sites, resulting from enzymatic perturbation of the binding of lipoprotein lipids and proteins, will be further evaluated. Models of lipoprotein organization together with hypotheses for their role in lipoprotein function will be formulated as the research progresses.