Chapter 16 _Part 1_

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Chapter 16 _Part 1_ Powered By Docstoc
					Chapter 16 (Part 1)

  Lipid Absorption and
• Transport water insoluble
  TAG, cholesterol and
  throughout circulatory
• Hydrophobic core containing
  TAG and cholesterol-esters
• Hydrophillic surface made of
  proteins (apoproteins) and
• Several different classes of lipoproteins.
• Chylomicrons deliver dietary fats to tissues
• VLDL, IDL and LDL transport endogenously
  synthesized TAG and cholesterol to tissues
• HDLs remove cholesterol from serum and
  tissues and transports it back to the liver.
• VLDL, IDL, LDL, and HDL named based on
  their density. Low density lipoproteins have
  high lipid to protein ratios. High density
  lipoproteins have low lipid to protein ratios.
• Lipases in capillaries of adipose and
  muscle tissues degrade TAG in
  VLDLs. VLDLs become IDLs.
• IDLs can then give up more lipid
  and become LDLs.
• LDLs are rich in cholesterol and
• VLDLs, IDLs, and LDLs all contain a large
  monomeric protein called ApoB-100.
• ApoB-100 forms amphipathic crust on
  lipoprotein surface.
• Chylomicrons contain analogous lipoprotein
• VLDLs and IDLs also possess a number of small
  weakly associated proteins that disassociate
  during lipoprotein degradation.
• Small apolipoproteins function to modulate the
  activity of enzymes involved in lipid mobilization
  and interactions with cell surface receptors.
            LDL Receptor
• Binds to ApoB-100.
• Found on cell surface of many cell types
• Mediates delivery of cholestrol by inducing
  endocytosis and fusion with lysosomes.
• Lysosomal lipases and proteases degrade the
  LDL. Cholesterol then incorporates into cell
  membranes or is stored as cholesterol-esters.
High LDL levels can lead to
  cardiovascular disease.
• LDL can be oxidized to form oxLDL
• oxLDL is taken up by immune cells called
• Macrophages become engorged to form
  foam cells.
• Foam cells become trapped in the walls
  of blood vessels and contribute to the
  formation of atherosclerotic plaques.
• Causes narrowing of the arteries which
  can lead to heart attacks.
Plaque Build up in Artery
   Absence of LDL Receptor Leads
     to Hypercholesteremia and
• Persons lacking the LDL receptor suffer from
  familial hypercholestermia
• Result of a mutation in a single autosomal gene
• Total plasma cholesterol and LDL levels are
• Homozygous indivdiuals have cholesterol levels
  of 680 mg/dL. Heterozygous individuals = 300
  mg/dL. Healthy person = <200 mg/dL.
• Most homozygous individuals die of
  cardiovascular disease in childhood.
     LDLs/HDLs and Cardiovascular
• LDL/HDL ratios are used as a diagnostic tool
  for signs of cardiovascular disease
• LDL = “Bad Cholesterol”
• HDL = “Good Cholesterol”
• A good LDL/HDL ratio is 3.5
• Protective role of HDL not clear.
• An esterase that breaks down oxidized lipids
  is associated with HDL. It is possible (but
  not proven) that this enzyme helps destroy
  Triacylglycerols are Highly
 Concentrated Energy Stores
• Complete oxidation of fatty acids yield 9
  kcal/gm while only 4 kcal/gm are
  generated from carbos and proteins.
• Fatty acids are more reduced than
  proteins or carbos.
• Since TAGs are non-polar and anhydrous
  (lacking hydration shell), can store more
  than 6 times as much energy per gm
  than glycogen.
Energy Reserves of a 150 lb Man

• 100,000 kcal of TAG, 25,000 kcal
  protein, 600 kcal glycogen, 40 kcal
• 24 lbs of body weight is TAG
• Would need 121lbs of glycogen to
  store the same amount of energy
Absorption and Mobilization of TAG
• Digestion of dietary lipids occurs in the small
• TAG must be broken down to fatty acids for
  absorption across intestinal epithelium.
• First TAG forms micelles with bile salts
  (amphipathic molecules drived from cholestrol)
• The micelles form to orient ester bonds of TAG
  towards the hydrophillic surface to allow water
  soluble lipases to cleave molecule.
Bile Salt
• Fatty acids and MAG enter mucosal cells where
  they are used to re-synthesize TAG
• TAG is then packaged into lipoprotein transport
  particles called chylomicrons (lipoprotein).
• Chylomicrons are mainly composed of TAG and
  apoprotein B-48. Also contain fat solubel vitamins
• Chylomicrons enter the lymph system and then the
  blood stream.
• Chylomicrons bind to membrane bound lipoprotein
  lipases at the surface of adipose and muscle cells.
            Storage of FAT
• TAG is delivered to
  adipose tissue in the
  form of chylomicrons and
• The TAG is hydrolyzed
  and enters adipose cell
  as free fatty acid and
• Fatty acids and MAG are
  re-esterified to form
• TAG coalesce in the
  cytoplasm of adipose
  cells to form large
           Mobilization of Fat
• Epinephrine,
  noepinephrine, glucgon
  hormones activate an
  adipose lipase.
• The hormones bind to
  the 7M receptor on
  outer surface of the
  adipose cell plasma
• Induces a G-protein
  mediated signal
  transduction pathway.
       Mobilization of Fat
• Free fatty acids are not soluble in blood plasma.
• Fatty acids are carried through the blood stream
  on proteins called serum albumins.
• Once fatty acids reach target cell it enters the
  cell and becomes esterified to CoA-SH and enters
  b-oxidation pathway
• Glycerol generated from fat breakdown is
  absorbed by the liver it can serve as an
  intermediate for glycolysis or gluconeogenesis.

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