Harpers

LIPID TRANSPORT & STORAGE / 209Dietary TGSMALLINTESTINELymphaticsLDL(apo B-100, E)receptorCholesterolFatty acidsNascentchylomicronAB-48TGCEApo C, Apo EAPCHDLCApoB-48A,Apo CEChylomicronB-48TGCACLIPOPROTEIN LIPASEEXTRAHEPATICTISSUESLIVERHLLRP receptorTGCEChylomicronremnantGlycerolFatty acidsFigure 25–3. Metabolic fate of chylomicrons. (A, apolipoprotein A; B-48, apolipoprotein B-48; C ,apolipoprotein C; E, apolipoprotein E; HDL, high-density lipoprotein; TG, triacylglycerol; C, cholesterol andcholesteryl ester; P, phospholipid; HL, hepatic lipase; LRP, LDL receptor-related protein.) Only the predominantlipids are shown.are believed to take part. Hepatic lipase has a dual role:(1) in acting as a ligand to the lipoprotein and (2) inhydrolyzing its triacylglycerol and phospholipid.VLDL is the precursor of IDL, which is then convertedto LDL. Only one molecule of apo B-100 ispresent in each of these lipoprotein particles, and this isconserved during the transformations. Thus, each LDLparticle is derived from only one VLDL particle (Figure25–4). Two possible fates await IDL. It can be taken upby the liver directly via the LDL (apo B-100, E) receptor,or it is converted to LDL. In humans, a relativelylarge proportion forms LDL, accounting for the increasedconcentrations of LDL in humans comparedwith many other mammals.LDL IS METABOLIZED VIATHE LDL RECEPTORThe liver and many extrahepatic tissues express theLDL (B-100, E) receptor. It is so designated because itis specific for apo B-100 but not B-48, which lacks thecarboxyl terminal domain of B-100 containing theLDL receptor ligand, and it also takes up lipoproteinsrich in apo E. This receptor is defective in familial hypercholesterolemia.Approximately 30% of LDL is degradedin extrahepatic tissues and 70% in the liver. Apositive correlation exists between the incidence ofcoronary atherosclerosis and the plasma concentrationof LDL cholesterol. For further discussion of theregulation of the LDL receptor, see Chapter 26.HDL TAKES PART IN BOTHLIPOPROTEIN TRIACYLGLYCEROL& CHOLESTEROL METABOLISMHDL is synthesized and secreted from both liver andintestine (Figure 25–5). However, apo C and apo E aresynthesized in the liver and transferred from liver HDLto intestinal HDL when the latter enters the plasma. Amajor function of HDL is to act as a repository for theapo C and apo E required in the metabolism of chylomicronsand VLDL. Nascent HDL consists of discoidphospholipid bilayers containing apo A and free cholesterol.These lipoproteins are similar to the particlesfound in the plasma of patients with a deficiency of theplasma enzyme lecithin:cholesterol acyltransferase(LCAT) and in the plasma of patients with obstructivejaundice. LCAT—and the LCAT activator apo A-I—bind to the disk, and the surface phospholipid and freecholesterol are converted into cholesteryl esters and