lesson 4

• Lipids


  Also known as fats, composed mostly of carbon-hydrogen bonds, rich source of energy, efficient way of storing excess calories as triglycerides in adipose tissues, play an integral part of the cell membrane of human cells (bilipid layer)

  
• Calorie computation


  1 g carbohydrates = 4 calories<|>1 gram protein = 4 calories<|>1 gram fat = 9 calories<|>1 g of alcohol = 7 grams
• Fatty acids


  • Linear chain of C-H bonds (hydrocarbon) that terminate with carboxylic acid group
  • Plasma - only few exist as free (unbound) fatty acids and most are bound to albumin to interact with water (since fatty acids are hydrophobic)
  • Some are found as part of triglycerides and phospholipids

  
• Saturated fatty acids


  Fatty acids with no double bonds
• Monounsaturated fatty acids


  Fatty acids with one double bond
• Polyunsaturated fatty acids


  Fatty acids with more than one double bond
• Cis fatty acids


  Hydrogen atoms near the double bonds are on the same side of the chain, kinky chains
• Trans fatty acids


  Hydrogen atoms are on the opposite sides of the chain, straight chains
• Cis fats are beneficial and can promote good cholesterol, while trans fats are considered harmful to cardiovascular health especially those trans fats which come from unnatural resources (e.g. hydrogenated oils in processed foods)

  
• Hydrogenation


  Commercial food establishments convert cis forms of fats to trans fats

  
• Triglycerides


  Has glycerol backbone esterified with 3 fatty acids, hydrophobic, neutral lipid, good energy source, 80% of the fats in the diet
• Phospholipids


  Same structure as triglycerides except they have only two esterified fatty acids, amphipathic (hydrophobic fatty acids and hydrophilic phosphate head)

  
• Cholesterol


  Composed of 4 fused hydrophobic rings and 1 hydrophilic hydroxyl group, amphipathic, exclusively synthesized by animals, readily catabolized by cells thus does not serve as source of energy, used for bile production and steroid hormone synthesis

  
• Cholesteryl ester


  Same structure as cholesterol except that the hydroxyl group is replaced by a fatty acid, hydrophobic, good source of energy
• Types of lipids


  • Triglycerides
  • Phospholipids
  • Cholesterol
  • Cholesteryl ester

  
• Majority of lipids are hydrophobic, plasma is composed of 90% lipids, lipids bind to proteins (water soluble) to form lipoproteins

  
• Lipoproteins


  Composed of lipids and proteins (apolipoproteins), main purpose is to transport energy, size correlates with its lipid content - higher lipid content, the lighter it is

  
• Apolipoproteins


  Protein portion of lipoproteins, found on the surface of the lipoproteins, help maintain the integrity of the lipoprotein, some bind to host cell receptors, some are activators or inhibitors

  
• Lipid absorption


  Fatty acids rapidly diffuse in the intestine, triglycerides are acted upon by pancreatic lipase, cholesterol is absorbed via the NPC1-L1 receptor, cholesteryl ester is acted upon by cholesteryl esterase, phospholipids are acted upon by phospholipase, short chain fatty acids are transported by albumin in the blood

  
• Chylomicrons


  Transport diet-derived lipids, contain large amount of triglycerides, large size enables it to reflect light and account for the turbidity of the postprandial plasma, lightweight causes it to float to the top of the stored plasma and form a creamy layer, good source of energy

  
• Exogenous pathway


  Newly synthesized chylomicrons in the intestine are secreted into the lymphatic ducts and eventually enter the circulation, in the tissues chylomicrons bind to heparan sulfate and other proteoglycans which promotes interaction with lipoprotein lipase, lipoprotein lipase hydrolyzes triglycerides on the chylomicrons generating fatty acids and glycerol, excess fatty acids are stored in adipose tissues as triglycerides, chylomicron remnants are then rapidly taken by the hepatocytes of the liver and are broken down

  
• Very low density lipoprotein (VLDL)


  Transports hepatic-derived lipids, transfers triglycerides from the liver to the peripheral tissues, contains large amount of triglycerides but not as much as chylomicrons, good source of energy, excess dietary intake of carbohydrates, saturated fatty acids and trans fatty acids enhance the hepatic synthesis of triglycerides

  
• Endogenous pathway


  VLDL undergoes a lipolytic process similar to that of chylomicrons, VLDL loses core lipids in the action of Lipoprotein lipase and becomes the VLDL remnants (or intermediate density lipoprotein - IDL), half of VLDL remnants are taken up by the liver and metabolized, the other half collect cholesterol and eventually becomes the IDL and LDL

  
• Low density lipoprotein (LDL)


  Transports cholesterol to the different cells in the body, taken up by the cells by binding to LDL receptors, too much LDL will deposit in the blood vessels, once bound to the receptors, the LDL are endocytosed and transported to the lysosomes for degradation, cholesterol may be used for membrane synthesis, synthesis of steroid hormones and stored as cholesteryl esters

  
• Reverse cholesterol pathway


  High density lipoproteins (HDL) - "good cholesterol", responsible for transporting cholesterol back to the liver for elimination or formation of bile acids

  
• DL loses core lipids in the action of Lipoprotein lipase


  Becomes the VLDL remnants (or intermediate density lipoprotein - IDL)

  
• VLDL remnants


  1. ½ are taken up by the liver and are metabolized just like the chylomicrons

  2. ½ of VLDL remnants collect cholesterol and eventually becomes the IDL and LDL

  
• LOW DENSITY LIPOPROTEIN (LDL)


  Transports cholesterol to the different cells in the body<|>Taken up by the cells by binding to LDL receptors present in cells<|>"bad" cholesterol<|>Too much LDL will deposit in the blood vessels<|>Once bound to the receptors, the LDL are endocytosed<|>Transported to the lysosomes for degradation<|>TAG component is acted upon by acid lipase to produce glycerol and fatty acids - source of energy<|>Cholesterol - may be used for membrane synthesis, synthesis of steroid hormones and stored as cholesteryl esters by the enzyme acyl-CoA or cholesterol acyltransferase (ACAT)

  
• REVERSE CHOLESTEROL PATHWAY


  Ibalik ang cholesterol sa liver for elimination or formation of bile acids

  
• High density lipoproteins (HDL) - "good cholesterol"


  Responsible for disposing cholesterol<|>Makes cholesterol to cholesteryl ester<|>Smallest but the most dense lipoprotein

  
• Apo-A1


  Activator of Lecithin Cholesterol Acyltransferase (LCAT)<|>Cholesterol from non-hepatic tissues is transferred to the liver for metabolism and excretion into the bile

  
• Lipid-poor discoid HDL particles, produced in the liver or the intestine, initiate the efflux of cholesterol and phospholipids from cell membranes via interaction with adenosine triphosphate-binding cassette transporter A1 (ABCA1)


  Subsequent action of Lecithin cholesterol acyl transferase or LCAT - the enzyme that helps esterifies excess cholesterol in pre beta-HDL particles and convert them to mature alpha HDL particles

  
• MATURE HDL CAN DELIVER CHOLESTEROL TO THE LIVER EITHER DIRECTLY

  1. Via scavenger receptor type B1 (SR-B1)

  2. Indirectly by exchange of cholesteryl esters to apoB-containing particle for TAG

  3. Cholesteryl esters can be exchanged for TAG in apoB-rich particles (LDL and VLDL) by cholesteryl ester transfer protein

  4. The uptake of apoB-rich particles via hepatic LDL receptors enable the delivery of cholesterol to the liver (around 50% of RCT)

  
• TANGIER DISEASE


  An inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood<|>Mutation to chromosome 9q31 led to a defective ABC1 transporter. These mutations prevent ABCA1 protein from effectively transporting cholesterol and phospholipids out of cells for pickup by ApoA1 in the bloodstream

  
• APOLIPOPROTEINS: A1


  Produced by the liver and intestine<|>Activator of LCAT enzyme<|>Major protein component of HDL particles in plasma<|>Angel = good = HDL

  
• APOLIPOPROTEINS: B100


  Synthesized in the liver along with the synthesis of VLDL<|>Important in the assembly of VLDL and cellular uptake of LDL<|>Present in VLDL, IDL and LDL<|>b = bad = b100 = LDL and ung ldl stuffs

  
• APOLIPOPROTEINS: B48


  ApoB48 is identical to the amino-terminal 48% of ApoB100<|>Involved in the synthesis, assembly and secretion of chylomicrons

  
• APOLIPOPROTEINS: CII


  Activator of LPL<|>Present in chylomicrons, VLDL, IDL and LDL

  
• APOLIPOPROTEINS: E


  Facilitates the binding of lipoprotein remnants to the liver for elimination or metabolism<|>Present in chylomicrons and HDL<|>In remnants only

  
• Blood levels of cholesterol and triglycerides increases with age