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					β-Oxidation
What Is Metabolism?
• Cell is the metabolic
  processing center
  – Nucleus
  – Cytoplasm
     • Cytosol + organelles
• ATP is the body’s energy
  currency
  – ATP = adenosine triphosphate
  – Form of energy cells use
• NAD and FAD: transport
  shuttles
  – Accept high energy electrons
    for use in ATP production
What Is Metabolism?
•Catabolism
 – Reactions that
   breakdown
   compounds
   into small units
•Anabolism
 – Reactions that
   build complex
   molecules from
   smaller ones
Energy: Fuel for Work
• Energy source
  – Chemical energy in carbohydrates, fat,
    protein
• Food energy to cellular energy
  – Stage 1: digestion, absorption,
    transport
  – Stage 2: breakdown of molecules
  – Stage 3: transfer of energy to a form
    cells can use
Fat
• Comes in many foods
• Broken down into free fatty acids which can be used
  to form ATP.
• A gram of fat yields about 9 kcal.
• Fat provides a sizable amount of energy (70,000 kcal)
  during prolonged, less intense exercise.
• Fat is stored intramuscularly or subcutaneously
• Fat is more difficult to break down and therefore it is
  less accessible for cellular metabolism.
• Low fat diets - increased risk of low intake of
  vitamins A, D, K and E.
Relation of Fatty Acids to Blood
     Sugar During Fasting
    4.5

     4

    3.5

     3

    2.5                                                   Fatty acids
     2                                                    Glucose

    1.5

     1

    0.5

     0
          4 hrs   8 hrs   12 hrs     16 hrs


                                   Stanley, et al, JIMD, 1989.
Breakdown and Release of Energy
• Extracting energy from fat
  – Split triglycerides into glycerol and fatty acids
  – Beta-oxidation
    • Breaks apart fatty acids into acetyl CoA
    • Transfers electrons to NAD and FAD
  – Citric acid cycle
    • Acetyl CoA from beta-oxidation enters cycle
  – Electron transport chain
  – End products of fat breakdown
    • ATP, H2O, CO2
Lipid Metabolism
Lipid Metabolism
Metabolic Pathways for Lipids
   a.Digestion of Triacylglycerols
   b.Oxidation of Fatty Acids
   c.ATP and Fatty Acid Oxidation
Metabolic Pathways for Lipids
                 Lipid Metabolism
      a.Digestion of Dietary Triacylglycerols
                                                      TRIACYLGLYCEROL

                                                                                         O
                                                                     O       CH2O        C    (CH2)14CH3

                                                    H3C(H2C)16       C   O   C       H

                                                                             CH2O        C    (CH2)14CH3

                                                          Pancreatic                     O

                                                           lipases               Intestinal
                                                                                  lipases
                                                                                     O

                                                                              HOC         (CH2)14CH3
• Occurs in duodenum                                                 CH2OH
                                               Glycerol         HO   C   H           + 3FA
• Facilitated by
                                                                     CH2OH
      • Bile salts (emulsification)                         O
                                                                             HOC         (CH2)14CH3
      • Alkaline medium (pancreatic juice)   H3C(H2C)16     COH
                                                                                 O
b. Oxidation of Fatty Acids
                Lipid Metabolism




carnitine
acyl
transferase I
activity is the
regulatory
rate-limiting
step in fatty
acid
catabolism
Beta Oxidation




                 R




                 R
Beta Oxidation
Beta Oxidation
Beta Oxidation
Beta Oxidation
Beta Oxidation
Beta Oxidation
Summary of steps in Beta Oxidation
I.   Fatty Acid Activation by Esterification
     with CoASH
II. Membrane Transport of Fatty Acyl CoA
     Esters
III. Carbon Backbone Reaction Sequence
     1.   Dehydrogenation
     2.   Hydration
     3.   Dehydrogenation
     4.   Carbon-Carbon Cleavage (Thiolase
          Reaction)
E.g:- Complete Beta Oxidation
of Palmitoyl CoA

CH3CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2COSCoA


                                   7 Cycles

                                                    +
            8 CH3COSCoA + 7 FADH2 + 7 NADH + 7 H
NB: Carnitine Supplemention
•   Conjugates toxic fats for excretion
•   Restores free CoA
•   Higher fat diets may increase carnitine losses
•   Will it cause accumulation of toxic fatty acids
    in the mitochondria?
Detailed Beta Oxidation of Fatty
Acids
Site:- Matrix of the mitochondria


    TRIACYLGLYCEROL
                                                                                      O
                               O
                                                                                 HOC       (CH2)14CH3
               O       CH2O    C   (CH2)14CH3                           CH2OH

  H3C(H2C)16   C   O   C   H                                       HO   C   H
                                                lipases
                       CH2O    C   (CH2)14CH3                  O        CH2OH
                                                                                HOC       (CH2)14CH3
                               O                  H3C(H2C)16   COH
                                                                                  O
 acyl CoASH synthetase
       (thiokinase)
                                             CoA

ATP + fatty acid           AMP- fatty acyl           fatty acyl CoA

                         PPi                   AMP
                                              cytosol

                                                                                            O
                     Coenzyme ASH                                             +                -
                                                                      (CH3) 3-N-CH2-CH-CH2-C-O
                                                                                                           O
                                                                                     OH                        C     O
                 O                                      O                         carnitine
                                                                                                       O       CH2
    H3C(H2C)16    COH                     H3C(H2C)16    CSCoA
                                                                                  H3C(H2C)16           C   O CH
                                                  fatty acyl CoA                                               CH2
                     2ATP     AMP + PPi                             CoASH            fatty acyl-
                                                                                                               N(CH3)3
                  acyl CoASH synthetase                                              carnitine
                        (thiokinase)                        carnitine acyl transferase I
 associated with ER and outer mito membrane                        CAT-I or CT-I
carnitine acyl transferase I
 activity is the regulatory
                                                                                        acyl carnitine/carnitine
 rate-limiting step in fatty         intermembrane space
                                                                                              transporter
      acid catabolism

                                     carnitine acyl transferase II          matrix
                                                                                       O
                                                             carnitine                     C       O
                                                                                 O         CH2
                                           O
                                                                   H3C(H2C)16    C    O CH
                             H3C(H2C)16       CSCoA
                                                                                           CH2
                                fatty acyl CoA              Coenzyme ASH                   N(CH3)3
                              acyl CoA dehydrogenase
                        O                                        O
                  
H3C(H2C)14   CH2 CH2 C        SCoA            H3C(H2C)14   CH CH C      SCoA               (crotonase)
                                                                                      -hydroxyacyl CoA
                                               trans-enoyl CoA                              hydratase
                                                                                            H    O

                                                                     H3C(H 2C)14       CH CH C       SCoA

                                                                                       OH
                                                                                   S-3-hydroxyacylCoA
                                                                                      hydroxyacyl CoA
                                                                                        dehydrogenase
                                                                                             H   O
                                               O

                 H3C(H2C)14   C   SCoA                                  H3C(H 2C)14    C     CH C        SCoA
                                           CH3 C    SCoA

                              O                                                        O

                  fatty acyl CoA(n-2)                        thiolase              3-ketoacylCoA
                              acyl CoA dehydrogenase

                        O                                        O
                  
H3C(H2C)14   CH2 CH2 C        SCoA            H3C(H2C)14   CH CH C      SCoA               (crotonase)
                                                                                      -hydroxyacyl CoA
                                  FAD FADH2    trans-enoyl CoA                              hydratase
                                                                                            H    O

                                                                     H3C(H 2C)14       CH CH C       SCoA

                                                                                       OH
                                                             NAD+                  S-3-hydroxyacylCoA

                                                            NADH +                    hydroxyacyl CoA
                                                                H+                      dehydrogenase
                                                                                             H   O
                                               O

                 H3C(H2C)14   C    SCoA                                 H3C(H 2C)14    C     CH C        SCoA
                                          CH3 C     SCoA

                              O                                                        O

                  fatty acyl CoA(n-2)                        thiolase              3-ketoacylCoA


                                               TCA
c. ATP and Fatty Acid Oxidation
Breakdown and Release of Energy
Energetics of Complete
Oxidation of Fatty Acids
                                           High Energy Phosphate
                                              Bonds Generated

  Palmitic Acid         Palmitoyl CoA            -2
                TCA Cycle
  CH3COSCoA              CO2 + H2O              108

                              Net               106

  106 High Energy Phosphate Bonds   G0’ = 3,233 KJ/Mole

				
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