Harpers

LIPID TRANSPORT & STORAGE / 211LIVERCC CE PLSR-B1HEPATICLIPASEA-1CCEPLHDL 2KidneyA-1Bile C andbile acidsSynthesisPL CA-1Preβ-HDLA-1CCE LCATPLHDL 3PLCDiscoidalHDLA-1LCATSynthesisABC-1SMALL INTESTINEPhospholipidbilayerTISSUESCFigure 25–5. Metabolism of high-density lipoprotein (HDL) in reverse cholesterol transport.(LCAT, lecithin:cholesterol acyltransferase; C, cholesterol; CE, cholesteryl ester; PL, phospholipid;A-I, apolipoprotein A-I; SR-B1, scavenger receptor B1; ABC-1, ATP binding cassette transporter 1.)Preβ-HDL, HDL 2 , HDL 3 —see Table 25–1. Surplus surface constituents from the action of lipoproteinlipase on chylomicrons and VLDL are another source of preβ-HDL. Hepatic lipase activity isincreased by androgens and decreased by estrogens, which may account for higher concentrationsof plasma HDL 2 in women.the blood of diet-induced hypercholesterolemic animals.It is rich in cholesterol, and its sole apolipoproteinis apo E. It appears that all plasma lipoproteins areinterrelated components of one or more metabolic cyclesthat together are responsible for the complexprocess of plasma lipid transport.THE LIVER PLAYS A CENTRAL ROLE INLIPID TRANSPORT & METABOLISMThe liver carries out the following major functions inlipid metabolism: (1) It facilitates the digestion and absorptionof lipids by the production of bile, which containscholesterol and bile salts synthesized within theliver de novo or from uptake of lipoprotein cholesterol(Chapter 26). (2) The liver has active enzyme systemsfor synthesizing and oxidizing fatty acids (Chapters 21and 22) and for synthesizing triacylglycerols and phospholipids(Chapter 24). (3) It converts fatty acids to ketonebodies (ketogenesis) (Chapter 22). (4) It plays anintegral part in the synthesis and metabolism of plasmalipoproteins (this chapter).Hepatic VLDL Secretion Is Relatedto Dietary & Hormonal StatusThe cellular events involved in VLDL formation andsecretion have been described above. Hepatic triacylglycerolsynthesis provides the immediate stimulus forthe formation and secretion of VLDL. The fatty acidsused are derived from two possible sources: (1) synthesiswithin the liver from acetyl-CoA derived mainlyfrom carbohydrate (perhaps not so important in humans)and (2) uptake of free fatty acids from the circulation.The first source is predominant in the well-fedcondition, when fatty acid synthesis is high and thelevel of circulating free fatty acids is low. As triacylglyceroldoes not normally accumulate in the liver underthis condition, it must be inferred that it is transportedfrom the liver in VLDL as rapidly as it is synthesizedand that the synthesis of apo B-100 is not rate-limiting.Free fatty acids from the circulation are the main sourceduring starvation, the feeding of high-fat diets, or in diabetesmellitus, when hepatic lipogenesis is inhibited.Factors that enhance both the synthesis of triacylglyceroland the secretion of VLDL by the liver include (1)