title: The promise of enzymes in therapy of hyperlipidemia.
abstract: Treatment of hyperlipidemias must be commenced in that intestinal segment where alimentary lipoprotein aggregate generation is initiated postprandially and the aggregates are still in nascent form. This is to prevent the formation of potentially pathological units that do not equilibrate with the blood colloid. The colloid chemical state of the alimentary lipoprotein entities in the systemic circulation is decisive for maintenance of their stability and for their disposal from the blood. The causes of impaired, "unripe," lipoprotein aggregate formation include: (a) the action of human pancreatic lipase is even normally a restricted and vulnerable process, (b) inadequate ratio of protein to fat to stabilize the aggregates, (c) defective proteolysis in the small intestine, and (d) the dual behavior of the surface tension-lowering agent, the lecithin antagonist cholesterol. On the one hand, cholesterol represents physicochemically the weakest link in the lipoprotein interfaces. On the other hand, an excess of cholesterol in lipoprotein interfaces decreases the stability of the surface film. This leads to changes in the decay of the entities and the cell surface-active lipid constituents of the "unripe" plasma lipoprotein colloid complexes can easily be adsorbed to the endothelial cell surface plasma membrane: the excess aggregate-cholesterol molecules simply join, or dissolve in, the cell membrane-cholesterol which thus acts as its own receptor or solvent: cholesterol dimers occur. This causes rigidity of the endothelial cell surface membrane and leads to impaired cell metabolism. The intima recognizes the impairment as a foreign body and initiates a physiological defense reaction including phagocytosis. The event may be still more dangerous if the adrenergic receptors of the autonomous nervous system involved in lipolysis with subsequent plasma efflux are simultaneously stimulated. The therapeutic measure indicated is production of balanced alimentary lipoprotein aggregates. This can be achieved by oral administration of (a) protease, and (b) non-specific micellar lipase. The lipase functions without restriction and can perform all the activities that human pancreatic lipase cannot. The enzymes utilized are of mold origin and generally available.
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D002628:Chemoreceptor Cells / Q000502:physiology; D002784:Cholesterol / Q000502:physiology; D002914:Chylomicrons / Q000097:blood / Q000528:radiation effects; D002986:Clinical Trials as Topic; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D008049:Lipase / Q000627:therapeutic use*; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice; D010447:Peptide Hydrolases / Q000627:therapeutic use*; D014176:Protein Biosynthesis; D011941:Receptors, Adrenergic / Q000502:physiology
chemical_list: D002914:Chylomicrons; D008074:Lipoproteins; D011941:Receptors, Adrenergic; D006632:Histamine; D002784:Cholesterol; D008049:Lipase; D010447:Peptide Hydrolases