lipid metabolism

• Triglycerides (fats and oils)


  Important dietary sources of energy
• Fat


  Major form of energy storage (9 Cal/g)
• Because it is water-insoluble, fat can be stored in larger quantities than carbohydrates
• Carbohydrate reserves are depleted after about 1 day without food, but stored fat can provide needed calories for 30-40 days
• Digestion of triglycerides


  Hydrolysis to glycerol, fatty acids, and monoglycerides

  
• Hydrolysis of phosphoglycerides


  To glycerol, fatty acids, phosphate groups, and aminoalcohols

  
• Chylomicrons


  Complexes of water-insoluble triglycerides, phosphoglycerides, and cholesterol with proteins for transport in lymph and blood

  
• Modification of chylomicrons by the liver


  Into smaller lipoprotein particles for transport in bloodstream

  
• Concentration of plasma lipids

  Increases after a meal, then returns to normal as a result of storage in fat depots and oxidation to provide energy
• Lipoproteins


  Classified by density, with increasing lipid concentration making the lipoprotein less dense

  
• Lipoproteins by density


  • Chylomicrons
  • Very-low-density lipoproteins (VLDL)
  • Low-density lipoproteins (LDL)
  • High-density lipoproteins (HDL)

  
• Cholesterol


  Involved in formation of cell membranes, insulation of nerves, synthesis of hormones, and digestion of food

  
• LDLs


  Transport cholesterol into artery walls, causing plaque formation and atherosclerosis
• HDLs


  Remove cholesterol from plaques in arteries and transport it to the liver for excretion or reuse
• Medications to lower cholesterol

  • Resin drugs (Questran, Colestid)
  • Lopid, or large doses of niacin
  • Statins (Mevacor, Zocor, Pravachol, Lipitor)

  
• Carbohydrates from dietary sources and glycogen catabolism are used preferentially for energy production by some tissues, such as the brain and active skeletal muscles
• Body stores of glycogen are depleted after only a few hours of fasting, requiring fatty acids stored in triglycerides to be used as energy sources
• Even when glycogen supplies are adequate, resting muscle and liver cells use energy from triglycerides because this conserves glycogen stores and glucose for use by brain cells and red blood cells

  
• Brain cells do not obtain nutrients from blood
• Red blood cells do not have mitochondria, and cannot do fatty acid oxidation
• Fat mobilization


  Endocrine system produces hormones like epinephrine that stimulate hydrolysis of triglycerides in adipose tissue to fatty acids and glycerol, which enter the bloodstream

  
• Transport of mobilized fatty acids

  Fatty acids form a lipoprotein with serum albumin in the blood, and glycerol dissolves in the blood

  
• Glycerol metabolism


  Glycerol is converted to dihydroxyacetone phosphate in two steps, which then enters glycolysis and can be converted to glucose through gluconeogenesis

  
• Activation of fatty acids

  Fatty acids are converted to fatty acyl CoA by reaction with coenzyme A, using ATP

  
• β-oxidation of fatty acids

  Fatty acyl CoA molecules undergo a catabolic process in the mitochondria to produce acetyl CoA, NADH, and FADH2

  
• The complete conversion of a fatty acyl CoA to acetyl CoA always produces one more molecule of acetyl CoA than of FADH2 or NADH

  
• The breakdown of 18-C stearic acid requires 8 passes through the β-oxidation spiral, and produces 9 acetyl CoA's, but only 8 FADH2 's and 8 NADH's

  
• Energy from fatty acids

  Activation of stearic acid consumes 2 ATP, but the β-oxidation produces 9 acetyl CoA's, 8 FADH2 's, and 8 NADH's, which can generate 90 ATP

  
• Fatty acid breakdown


  1. Acetyl CoA, NADH, and FADH2 produced

  2. Four-carbon chain of butyryl CoA passes through β-oxidation

  3. Produces FADH2, NADH, and two acetyl CoA's

  
• The complete conversion of a fatty acyl CoA to two carbon fragments of acetyl CoA always produces one more molecule of acetyl CoA than of FADH2 or NADH

  
• The breakdown of 18-C stearic acid requires 8 passes through the spiral, and produces 9 acetyl CoA's, but only 8 FADH2 's and 8 NADH's

  
• Activation of stearic acid

  Hydrolysis of 2 ATP's

  
• Fatty acid breakdown


  Produces 9 acetyl CoA's, 8 FADH2 's, and 8 NADH's

  
• Acetyl CoA can enter the citric acid cycle / electron transport chain and form 10 ATP's

  
• Each FADH2 yields 1.5 ATP's, and each NADH yields 2.5 ATP's
• From one 18-C stearic acid molecule, 120 molecules of ATP are formed

  
• On the basis of an equal number of carbons, lipids are nearly 25% more efficient than carbohydrates as energy-storage systems

  
• On an equal-mass basis, lipids contain more than twice the energy of carbohydrates

  
• Lipids are a more reduced form of fuel, while glucose is already partially oxidized
• Changes caused by fasting

  1. Fatty acids become the body's primary energy source

  2. Glycolysis decreases

  3. Oxaloacetate used for gluconeogenesis

  4. Citric acid cycle activity reduced

  5. Acetyl CoA builds up