Cholesterol Ester Metabolism

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Abstract
Abundant evidence exists that free cholesterol is an essential component of cellular and subcellular membranes in all cells. Cholesterol also serves as the biosynthetic precursor for several vital compounds, including a variety of steroid hormones and bile acids, many of which act biologically as important regulatory compounds. Including, in mammals, steroid hormones and vitamins A and D. Steroids and other isoprene derivatives also play important regulatory roles in other phyla. Several insect hormones, for example, appear to be isoprenoid derivatives; one may be cholesterol itself. Since many of the floral scents of plants are terpenes, these compounds might play important roles regulating the sexual life of the plants. The molecular sites of action of these regulatory compounds are not known. In mammals many of these compounds appear to act at membranes, by affecting membrane structure or the transport of ions or molecules. Thus aldosterone affects Na+ and K+ transport across a variety of membranes; vitamin D controls Caz+ ion transportacross the intestinal mucosa; and vitamin A importantly affects the stability of lysosomal and other membranes. Similarly, bile acids are critically involved in fat transport across the intestinal mucosa. The chemical relationship between these compounds and cholesterol might be somehow involved in their effects on biological membranes, either in molecular sites of action or the evolution of such compounds. Cholesterol esters apparently serve different metabolic roles from free cholesterol, perhaps including an important structural role in plasma lipoprotein molecules. Cholesterol esters are actively metabolized and sometimes abundantly present in those tissues where cholesterol is converted to other metabolically important compounds. The organs studied most are the liver (converts cholesterol to bile acids) and the adrenal gland (synthesizes steroid hormones). In both, cholesterol esters may be the immediate precursor for the biosynthesis of the cholesterol metabolite. It is more likely that cholesterol esters partly serve as a reservoir of cholesterol molecules in these locations (particularly in the adrenals). Enzymatic activity for cholesterol ester formation and hydrolysis may be found in gonads, placenta, and other tissues that synthesize steroid hormones. The small amounts of cholesterol esters found in most other tissues may represent a small reservoir of cholesterol molecules for utilization during membrane turnover. These esters may also participate in the structure of certain particular membranes or portions of membranes.