Harpers

•••208 / CHAPTER 25AIntestinal lumenB•••••••••••••••••••••••••••••••••••RER•• ••••••• ••••••••••••••••••••••••••••••••• ••••••••••••••••••••••••••••••••••SERG•••••••••••••• ••••••••••••••••••••••••••••••••••• • ••••••• •• •••••••• • • • • • • •RERSERNNCFenestraGVLDLBilecanaliculusSDEndothelialcellBloodcapillaryLymph vessel leadingto thoracic ductELumen of blood sinusoidFigure 25–2. The formation and secretion of (A) chylomicrons by an intestinal cell and (B) very low densitylipoproteins by a hepatic cell. (RER, rough endoplasmic reticulum; SER, smooth endoplasmic reticulum; G, Golgiapparatus; N, nucleus; C, chylomicrons; VLDL, very low density lipoproteins; E, endothelium; SD, space of Disse,containing blood plasma.) Apolipoprotein B, synthesized in the RER, is incorporated into lipoproteins in the SER,the main site of synthesis of triacylglycerol. After addition of carbohydrate residues in G, they are released fromthe cell by reverse pinocytosis. Chylomicrons pass into the lymphatic system. VLDL are secreted into the spaceof Disse and then into the hepatic sinusoids through fenestrae in the endothelial lining.and apo C-III act as inhibitors. Hydrolysis takes placewhile the lipoproteins are attached to the enzyme onthe endothelium. Triacylglycerol is hydrolyzed progressivelythrough a diacylglycerol to a monoacylglycerolthat is finally hydrolyzed to free fatty acid plus glycerol.Some of the released free fatty acids return to the circulation,attached to albumin, but the bulk is transportedinto the tissue (Figures 25–3 and 25–4). Heart lipoproteinlipase has a low K m for triacylglycerol, about onetenthof that for the enzyme in adipose tissue. This enablesthe delivery of fatty acids from triacylglycerol tobe redirected from adipose tissue to the heart in thestarved state when the plasma triacylglycerol decreases.A similar redirection to the mammary gland occursduring lactation, allowing uptake of lipoprotein triacylglycerolfatty acid for milk fat synthesis. The VLDL receptorplays an important part in the delivery of fattyacids from VLDL triacylglycerol to adipocytes by bindingVLDL and bringing it into close contact withlipoprotein lipase. In adipose tissue, insulin enhanceslipoprotein lipase synthesis in adipocytes and itstranslocation to the luminal surface of the capillary endothelium.The Action of Lipoprotein Lipase FormsRemnant LipoproteinsReaction with lipoprotein lipase results in the loss ofapproximately 90% of the triacylglycerol of chylomicronsand in the loss of apo C (which returns to HDL)but not apo E, which is retained. The resulting chylomicronremnant is about half the diameter of theparent chylomicron and is relatively enriched in cholesteroland cholesteryl esters because of the loss of triacylglycerol(Figure 25–3). Similar changes occur toVLDL, with the formation of VLDL remnants or IDL(intermediate-density lipoprotein) (Figure 25–4).The Liver Is Responsible for the Uptakeof Remnant LipoproteinsChylomicron remnants are taken up by the liver by receptor-mediatedendocytosis, and the cholesteryl estersand triacylglycerols are hydrolyzed and metabolized.Uptake is mediated by a receptor specific for apo E(Figure 25–3), and both the LDL (apo B-100, E) receptorand the LRP (LDL receptor-related protein)