Dietary Strategies and Novel Pharmaceutical Approaches Targeting Serum ApoA-I Metabolism: A Systematic Overview

Figure 1

Simplified scheme of the synthesis, metabolism, and clearance of apoA-I. ApoA-I is synthesized in cells of the liver and intestine as pre-pro-apoA-I. After translocation to the endoplasmic reticulum, the preprotein is cleaved of and pro-apoA-I is secreted into blood and lymph. In the circulation, the prosegment is directly cleaved of by Bone Morphogenetic Protein-1 (BMP-1) and Procollagen C-proteinase Enhancer-2 Protein (PCPE2). After this, apoA-I accepts cholesterol and phospholipids from ABCA1, forming a pre-β HDL particle. In the circulation, lecithin-cholesterol acyltransferase esterifies (LCAT) the free cholesterol in these pre-β HDL particles, forming HDL₃ and finally HDL₂, as indicated by the black arrows. After binding of HDL₂ to SR-B1 on the liver, the cholesterol esters are taken up and lipid-depleted apoA-I is returned to the circulation. These apoA-I-rich particles can again acquire cholesterol and phospholipids or can be cleared from the circulation. Clearance will take place for 70% by the kidney, where apoA-I is broken down into amino acids and ultimately excreted in the urine. 26% of the free apoA-I will be cleared by the liver, and apoA-I catabolic products will then be excreted via biliary secretion into the gut and further digested and absorbed or excreted from the body through the feces. 4% of the free apoA-I will go to other tissues and finally will end up in the urine, as indicated by the blue arrows.