Catabolism of Lipids

• Lipid Catabolism

  • Lipids play roles in energy metabolism as well as in a variety of other processes: their roles as membrane constituents, hormones, fat-soluble vitamins, thermal insulators, and signaling molecule.
• Fatty acyl CoAs are formed by esterification between an RCOOH group and coenzyme A.
• • Certain tissues, such as heart and liver, obtain as much as 80% of their energy needs from fat oxidation.
• Triacylglycerols play roles other than in energy storage

  Fat serves to cushion organs against shock, and it provides an efficient thermal insulator, particularly in marine mammals, which must maintain a body temperature far higher than that of the seawater in which they live
• Lipis Catabolism

  • Blood lipid concentration increases after a meal and returns to normal due to storage of fat in depots and undergo oxidation to provide energy
• "Good/Bad" Cholesterol

  • LDL called bad cholesterol because of link to atherosclerosis
  • HDL called good cholesterol because high HDL levels counter atherosclerosis by transporting cholesterol back to the liver from peripheral tissues
• Levels of LDL and HDL

  • Most of the cholesterol is carried by LDL.
  • Normal plasma levels are 175 mg/100 mL.
  • If there are sufficient LDL receptors on the surface of cells,
  • LDL is removed from circulation and its concentration in blood plasma drops.
  • The number of LDL receptors is controlled by a feedback mechanism.
  • When the concentration of cholesterol inside cells is high, the synthesis of LDL receptors is suppressed.
  • In the disease called famelial hypercholesterolemia, there are not enough LDL receptors and plasma levels of cholesterol may rise as high as 680 mg/100 mL.
• Levels of LDL and HDL

  • High LDL together with low HDL is a symptom of faulty cholesterol transport and a warning of possible atherosclerosis.
  • The serum cholesterol level controls cholesterol synthesis in the liver.
  • When serum cholesterol is high, its synthesis in the liver is low, and vice versa.
  • The commonly used statin drugs inhibit the synthesis of cholesterol by blocking HMG-CoA reductase.
• Levels of LDL and HDL

  • Excess LDL cholesterol accumulates in the inner arterial walls, forming fatty streaks, which attract white blood cells (macrophages).
  • If cholesterol levels are too high for its subsequent removal into the bloodstream, these macrophages become engorged with fatty deposits, which then harden into plaque; this condition, called atherosclerosis, ultimately blocks key blood vessels and causes myocardial infarctions, or heart attacks.
• Triacylglycerol Storage and Mobilization

  • LIPOLYSIS - mobilization of lipids
  • When ATP levels in the cells (eg. liver) goes down, the organism utilizes its fat reserves.
  • The mobilization of triglycerides is initiated by several hormones by activating cAMP (activate hormone sensitive lipase; HSL) which releases fatty acids and glycerol from adipocytes.
• Glycerol Catabolism

  • Taken to liver by blood -- converted to dihydroxyacetone phosphate in two steps:
  • Phosphorylation of primary hydroxyl group of the glycerol
  • Secondary alcohol group of glycerol is oxidized to ketone
  • Glycerol enters glycolysis via dihydroxyacetone phosphate
  • Via glycolysis, it is converted to pyruvate to be used for energy production.
  • Can be converted to glucose from pyruvate via gluconeogenesis
• Overview of the Fatty Acid Oxidation Pathway

  • Fatty acids are transported to the mitochondria via acyl carnitine shuttle system, and will go β-oxidation
• Knoops β-Oxidation

  • The activated fatty acyl CoA will undergo a series of reactions catalyzed by enzymes localized in the mitochondrial matrix that cleaves carbon atoms two at a time from the carboxyl end of a fatty acid.
  • The reaction is called β-oxidation (fatty acid spiral) because it involves the reactions of β-C leading to its oxidation.
  • For even numbered fatty acids, the end products are acetyl CoA, NADH and FADH2
  • For odd numbered fatty acids, propionylCoA is produced
• Activation: The fatty acid is activated in the cytosol by conversion to an acyl CoA.

  • Activation is equivalent to the hydrolysis of two high-energy phosphate anhydrides.
  • The carnitine acyltransferase system, for transport of fatty acyl-CoAs into mitochondria.
  • The resulting product is an acetyl CoA molecule and a new acyl CoA molecule that is shorter by two carbon atoms than its predecessor: FADH2 and NADH are also produced.
  • Acetyl CoA will then processed in Citric Acid Cycle
• Oxidation of Unsaturated Fatty Acids

  • For unsaturated fatty acids, the presence of double bond will eliminate one desaturation reaction.
  • Since the β-oxidation reaction for the carbons containing a double bond would bypass the elimination reaction, one FADH2 is not produced per double bond.
  • The ATP yield for unsaturated fatty acids will decrease by 2 ATP units per double bond.
• Lipid Catabolism

  • A mammal contains 5% to 25% or more of its body weight as lipid, with as much as 90% of this lipid in the form of triacylglycerols (triglycerides).
• Lipid Catabolism

  • The term fat, or neutral fat, refers to this most abundant class of lipids
• Lipid Catabolism

  • Most of this fat is stored in adipose tissue (adipocytes) and constitutes the primary energy reserve, which is burned at a later time as needed.
• Lipid Catabolism

  • Most of the energy derived from fat breakdown comes from oxidation of the constituent fatty acids.
• Lipid Catabolism

  • In plant, seeds store great quantities of fat to provide energy to the developing plant embryo.
• Lipid Catabolism

  • Because plant lipids contain mostly unsaturated fatty acids, the triacylglycerols of seeds are largely in the form of liquid oils
• Lipid Catabolism

  Concentration of plasma lipids usually begins to rise within 2 hours after a meal, reaches a peak in 4 to 6 hours, and then drops rather rapidly to a normal level