Lipid Transport_ Classes of Lipoproteins_ Reverse Cholesterol by linzhengnd


									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
                                                      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
                                              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
      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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