Oxidation of Fatty Acids.

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Oxidation of Fatty Acids.

• Digestion of Triacylglycerols
• Beta-Oxidation of Fatty Acids
• ATP and Fatty Acid Oxidation

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The body fat is our major source of stored energy.

• Our adipose tissue is made of fat cells
  adipocytes.
• A typical 70 kg (150 lb) person has about 135000
  kcal of energy stored as fat 24000 kcal as
  protein 720 kcal as glycogen reserves and 80
  kcal as blood glucose.
• The energy available from stored fats is about 85
  of the total energy available in the body.

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Digestion of Triacylglycerols

• In the digestion of fats (triacylglycerols)
• Bile salts break fat globules into micelles in
  the small intestine.
• Pancreatic lipases hydrolyze ester bonds to form
  monoacylglycerols and fatty acids which
  recombine in the intestinal lining.
• Lipoproteins form and transport triacylglycerols
  to the cells of the heart muscle and adipose
  tissues.
• Brain and red blood cells cannot utilize fatty
  acids because fatty acids cannot diffuse across
  the blood-brain barrier and red blood cells have
  no mitochondria where fatty acids are oxidized.
  (Glucose and glycogen are the only source of
  energy for the brain and red blood cells.)

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Digestion of Triacylglycerols
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Fat Mobilization

• Fat mobilization
• Breaks down triacylglycerols in adipose tissue to
  fatty acids and glycerol.
• Occurs when hormones glucagon and epinephrine are
  secreted into the bloodstream and bind to the
  receptors on the membrane of adipose cells
  activating the enzymes within the fat cells that
  begin the hydrolysis of triacylglycerols.
• Fatty acids are hydrolyzed initially from C1 or
  C3 of the fat.
• Lipases
• Triacylglycerols 3H2OGlycerol 3Fatty acids

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Metabolism of Glycerol.

• Using two steps enzymes in the liver convert
  glycerol to dihydroxyacetone phosphate which is
  an intermediate in several metabolic pathways
  including glycolysis and gluconeogenesis.
• 1st step glycerol is phosphorylated using ATP to
  yield glycerol-3-phosphate.
• 2nd step the hydroxyl group is oxidized to yield
  dihydroxyacetone phosphate.
• The overall reaction for the metabolism of
  glycerol
• Glycerol ATP NAD Dihydroxyacetone
  phosphate ADP NADH H

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Fatty Acid Activation

• Fatty acid activation
• Allows the fatty acids in the cytosol to enter
  the mitochondria for oxidation.
• Combines a fatty acid with CoA to yield fatty
  acyl CoA that combines with carnitine.

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Fatty Acid Activation

• Fatty acyl-carnitine transports the fatty acid
  into the matrix.
• The fatty acid acyl group recombines with CoA for
  oxidation.

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Fatty Acid Activation

• Fatty acid activation is complex but it
  regulates the degradation and synthesis of fatty
  acids.

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Beta-Oxidation of Fatty Acids

• In reaction 1 oxidation
• Removes H atoms from the and carbons.
• Forms a trans CC bond.
• Reduces FAD to FADH2.

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Beta-Oxidation of Fatty Acids

• In reaction 2 hydration
• Adds water across the trans CC bond.
• Forms a hydroxyl group (OH) on the carbon.

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Beta ()-Oxidation of Fatty Acids

• In reaction 3 a second oxidation
• Oxidizes the hydroxyl group.
• Forms a keto group on the carbon.

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Beta ()-Oxidation of Fatty Acids

• In Reaction 4 acetyl CoA is cleaved
• By splitting the bond between the and
  carbons.
• To form a shortened fatty acyl CoA that repeats
  steps 1 - 4 of -oxidation.

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Beta ()-Oxidation of Myristic (C14) Acid
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Beta ()-Oxidation of Myristic (C14) Acid
(continued)
7 Acetyl CoA
6 cycles
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Cycles of -Oxidation

• The length of a fatty acid
• Determines the number of oxidations and
• The total number of acetyl CoA groups.
• Carbons in Acetyl CoA -Oxidation Cycles
• Fatty Acid (C/2) (C/2 1)
• 12 6 5
• 14 7 6
• 16 8 7
• 18 9 8

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-Oxidation and ATP

• Activation of a fatty acid requires
• 2 ATP
• One cycle of oxidation of a fatty acid produces
• 1 NADH 3 ATP
• 1 FADH2 2 ATP
• Acetyl CoA entering the citric acid cycle
  produces
• 1 Acetyl CoA 12 ATP

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ATP for Lauric Acid C12

• ATP production for lauric acid (12 carbons)
• Activation of lauric acid -2 ATP
• 6 Acetyl CoA
• 6 acetyl CoA x 12 ATP/acetyl CoA 72 ATP
• 5 Oxidation cycles
• 5 NADH x 3ATP/NADH 15 ATP
• 5 FADH2 x 2ATP/FADH2 10 ATP
• Total 95 ATP

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Oxidation of Unsaturated Fatty Acids.

• Oxidation of monounsaturated fatty acyl-CoA
  requires additional reaction performed with the
  help of the enzyme isomerase.
• Double bonds in the unsaturated fatty acids are
  in the cis configuration and cannot be acted upon
  by enoyl-CoA hydratase (the enzyme catalyzing the
  addition of water to the trans double bond
  generated during ß-oxidation.
• Enoyl-CoA isomerase repositions the double bond
  converting the cis isomer to trans isomer a
  normal intermediate in ß-oxidation.

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Oxidation of polyunsaturated fatty acids.

• Requires two additional reactions and a second
  enzyme reductase in addition to isomerase.
• NADPH-dependent 24-dienoyl-CoA reductase
  converts trans-2 cis-4-dienoyl-CoA intermediate
  into the trans-2-enoyl-CoA substrate necessary
  for ß-oxidation.

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Oxidation of odd-chain fatty acids.

• Odd-carbon fatty acids are oxidized by the same
  pathway as even-carbon acids until three-carbon
  propionyl-CoA is formed.
• After that three additional reactions are
  required involving three enzymes.
• Propionyl-CoA is carboxylated by propionyl-CoA
  carboxylase (with the cofactor biotin) to form
  the D stereoisomer of methylmalonyl-CoA (The
  formation of the carboxybiotin intermediate
  requires energy from ATP).
• D-methylmalonyl-CoA is changed into
  L-methylmalonyl-CoA by methylmalonyl-CoA
  epimerase.
• L-methylmalonyl-CoA undergoes an intramolecular
  rearrangment to form succinyl-CoA which enters
  the citric acid cycle. This rearrangment is
  catalyzed by methylmalonyl-CoA mutase which
  requires coenzyme B12 derived from vitamin B12
  (cobalamin).

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Overview of Metabolism

• In metabolism
• Catabolic pathways degrade large molecules.
• Anabolic pathway synthesize molecules.
• Branch points determine which compounds are
  degraded to acetyl CoA to meet energy needs or
  converted to glycogen for storage.

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