Lipid Transport, Classes of Lipoproteins, Reverse Cholesterol Transport, Effects of Sex Hormones on Hepatic Lipase and HDL I. Lipid Transport a. Lipids are transported for tissue to tissue in the blood via Lipoproteins b. Lipoproteins have a lipid core, and a singles layer of amphipathic phospholipids. i. The surface layer of a lipoprotein has 1. A phospholipid single layer 2. Cholesterol 3. Apolipoproteins (apoproteins) a. Different Apoproteins have different locations and functions i. Apoprotein A 1. Apoprotein A is found in HDL 2. Apoprotein A is an activator for the LCAT enzyme 3. Apoprotein A is the ligand of the HDL molecule 4. Apoprotein A is protective against CVD ii. Apoprotein B48 1. Apoprotein B48 is found in: a. Chylomicrons b. VLDL c. LDL 2. Apoprotein B48 is used as the ligand of Chylomicrons, LDL, and VLDL iii. Apoprotein B100 1. Apoprotein B100 is also found in the chylomicrons, LDL, and VLVL molecules 2. Apoprotein B100 is also used as the ligand for Chylomicrons VLDL and LDL iv. Apoprotein C 1. Apoprotein C is a structural protein for the lipoprotein v. Apoprotein E 1. Apoprotein E is the ligand of the lipoprotein II. Classes of Lipoproteins a. Chylomicrons i. Chylomicrons transport all dietary lipids into the circulation from the intestines ii. Chylomicrons get cleared from the blood very rapidly iii. Liver does not metabolize Native Chylomicrons 1. The liver waits for the chylomicrons to be broken down a little bit before it metabolizes the lipids. b. VLVL i. VLDLs transport lipids from the liver to other tissues ii. Lipoprotein Lipase is the enzyme on the wall of the capillaries of extrahepatic tissues that anchor the VLDL 1. Anchoring is done by heparin sulfate 2. Once anchored, lipoprotein lipase liberates some free fatty acids to go into the tissue and releases the glycerol into the blood stream 3. One the VLDL is smaller, it becomes more dense a. The VLDL become an LDL c. LDL i. LDL consists mainly of cholesterol since most of the triglycerides of the LDL were just liberated by the lipoprotein lipase. ii. The more LDL concentration in plasma, the higher the risk of atherosclerosis iii. Receptors for LDL 1. Lipoprotein B100 receptor for LDL 2. Lipoprotein E receptor for LDL 3. Receptors for LDL are found primarily in a. Fibroblasts b. Lymphocytes c. Aterial smooth muscle cells d. Liver iv. 70% of all LDL’s are degraded in the liver d. HDL i. HDL is synthesized and secreted by the liver and the intestines ii. HDLs contain 3 Apoproteins 1. HDLs contain Apoprotein A a. Intestinal HDL’s only contain Apoprotein A 2. HDL’s contain Apoprotein C 3. HDL’s contain Apoprotein E iii. HDLs are involved in Reverse Cholesterol Transport III. Reverse Cholesterol Transport a. Liver synthesized “nascent” or “discoidal” HDL b. HDL roams around from the liver to the tissues uptaking and esterifying cholesterol for the tissue i. The enzyme that allows this uptake and esterification is called Lecithin- cholesterol acyltransferase 1. Lecithin-Cholesterol AcylTransferase converts cholesterol to cholesterol esters and lysolecithin a. Cholesterol esters move to the core of the HDL b. Lysolecithin is then transferred to albumin. ii. Once the cholesterol is taken up and esterified, the HDL is now HDL3 iii. As HDL3 grows it becomes less dense and earns the name HDL2 c. When the HDL 2 comes back around to the Liver, Hepatic Lipase allows the unlading of the cholesterol and the cholesterol esters out into the liver. i. The lightened load of the HDL2 makes it smaller and more dense, back into the HDL3 d. HDL3 then reenters the circulation. IV. Effect of Sex Hormones on Hepatic Lipase and HDL a. Once hepatic lipase allows the cholesterol off the HDL, the cholesterol can reenter the blood as LDL. b. Androgens increase the activity of Hepatic Lipase i. Increased activity of Hepatic Lipase means less HDL in blood ii. Men have lower HDL blood counts c. Estrogens decrease the activity of Hepatic Lipase i. Decreased activity of Hepatic Lipase means more HDL in blood ii. Menstruating women (still with estrogen) have higher HDL blood counts d. Factors that Increase HDL i. Less calories usually means less triglycerides ii. Increase exercise 1. Increase exercise increases the activity of Lipoprotein lipase 2. The more cholesterol in the tissue iii. Pre-menopausal women have estrogen 1. Estrogen reduces the activity of hepatic lipase, and since hepatic lipase reduces HDL, less hepatic lipase activity means more HDL.
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