KREB’S CYCLE  (TRICARBOXYLIC ACID (TCA)CYCLE/CITRIC ACID CYCLE) BIOCHEMISTRY LEC WEEK 3
METABOLIC PATHWAYS A series of consecutive biochemical reactions catalyzed by enzymes that produce a specific end product. Catabolism- the breakdown of food stuffs to simple organic chemicals. Anabolism- the synthesis of biomolecules from simple organic chemicals.
METABOLIC PATHWAYS Very Few metabolites are used to synthesize a large variety of biomolecules : Acetyl-Coenzyme A (acetyl-CoA) Pyruvate Citrate acid cycle intermediates
METABOLIC PATHWAYS Three main pathways for energy production: Glycolysis Citric acid cycle Oxidative-Phosphorylation
METABOLIC PATHWAYS Certain pathways are involved in both breakdown and buildup of molecules these pathways are called  amphibolic .  The citric acid cycle is an example of this.
OVERALL GOAL/IMPORTANCE  Makes ATP Makes NADH  Makes FADH 2 A cyclical series of biochemical reactions that is fundamental to the metabolism of aerobic organisms, i.e. animals, plants, and many microorganisms
Geography Krebs in mitochondrial matrix Mitochondrion Outer membrane very permeable Space between membranes called intermembrane space  Inner membrane (cristae) Permeable to pyruvate, Impermeable to fatty acids, NAD, etc Matrix is inside inner membrane
The citric acid cycle enzymes are found in the matrix of the mitochondria
OVERVIEW Described by Hans Adolf Krebs in 1937 A feature of cell chemistry shared by all types of life. A complex series of reactions beginning and ending with the compound oxaloacetate. The cycle produces carbon dioxide and the energy-rich compound ATP.
OVERVIEW Eight successive reaction steps. The six carbon citrate is formed from two carbon acetyl-CoA and four carbon oxaloacetate. Oxidation of citrate yields CO2 and regenerates oxaloacetate. The energy released is captured in the reduced coenzymes NADH and FADH2.
Conversion of pyruvate to Acetyl CoA 2 per glucose (all of Kreb’s) Oxidative decarboxylation Makes NADH
Fates of Acetyl CoA In the presence of CHO Metabolized to CO 2 , NADH, FADH 2 ,GTP and, ultimately, ATP If energy not being used (Lots of ATP present) Made into fat If energy being used, but no CHO present Starvation Forms ketone bodies (see fat metabolism slides) Danger!
Kreb’s Cycle
1. Citrate Synthase Reaction
2. Aconitase Reaction Forms isocitrate
3. Isocitrate Dehydrogenase All dehydrogenase reactions make NADH or FADH 2
4.  α -ketoglutarate dehydrogenase Same as pyruvate dehydrogenase reaction
5. Succinyl CoA synthetase Coupled to synthesis of GTP GTP very similar to ATP and interconverted later
6. Succinate dehydrogenase Dehydrogenation Uses FAD
7. Fumarase Addition of water to a double bond
8. Malate Dehydrogenase Makes NADH Regenerates oxaloacetate for another round
Net From Kreb’s Oxidative process 3 NADH FADH 2 GTP X 2 per glucose 6 NADH 2 FADH 2 2 GTP All ultimately turned into ATP  (oxidative phosphorylation)

Kreb's cycle (1)

  • 1.
    KREB’S CYCLE (TRICARBOXYLIC ACID (TCA)CYCLE/CITRIC ACID CYCLE) BIOCHEMISTRY LEC WEEK 3
  • 2.
    METABOLIC PATHWAYS Aseries of consecutive biochemical reactions catalyzed by enzymes that produce a specific end product. Catabolism- the breakdown of food stuffs to simple organic chemicals. Anabolism- the synthesis of biomolecules from simple organic chemicals.
  • 3.
    METABOLIC PATHWAYS VeryFew metabolites are used to synthesize a large variety of biomolecules : Acetyl-Coenzyme A (acetyl-CoA) Pyruvate Citrate acid cycle intermediates
  • 4.
    METABOLIC PATHWAYS Threemain pathways for energy production: Glycolysis Citric acid cycle Oxidative-Phosphorylation
  • 5.
    METABOLIC PATHWAYS Certainpathways are involved in both breakdown and buildup of molecules these pathways are called amphibolic . The citric acid cycle is an example of this.
  • 6.
    OVERALL GOAL/IMPORTANCE Makes ATP Makes NADH Makes FADH 2 A cyclical series of biochemical reactions that is fundamental to the metabolism of aerobic organisms, i.e. animals, plants, and many microorganisms
  • 7.
    Geography Krebs inmitochondrial matrix Mitochondrion Outer membrane very permeable Space between membranes called intermembrane space Inner membrane (cristae) Permeable to pyruvate, Impermeable to fatty acids, NAD, etc Matrix is inside inner membrane
  • 8.
    The citric acidcycle enzymes are found in the matrix of the mitochondria
  • 9.
    OVERVIEW Described byHans Adolf Krebs in 1937 A feature of cell chemistry shared by all types of life. A complex series of reactions beginning and ending with the compound oxaloacetate. The cycle produces carbon dioxide and the energy-rich compound ATP.
  • 10.
    OVERVIEW Eight successivereaction steps. The six carbon citrate is formed from two carbon acetyl-CoA and four carbon oxaloacetate. Oxidation of citrate yields CO2 and regenerates oxaloacetate. The energy released is captured in the reduced coenzymes NADH and FADH2.
  • 11.
    Conversion of pyruvateto Acetyl CoA 2 per glucose (all of Kreb’s) Oxidative decarboxylation Makes NADH
  • 12.
    Fates of AcetylCoA In the presence of CHO Metabolized to CO 2 , NADH, FADH 2 ,GTP and, ultimately, ATP If energy not being used (Lots of ATP present) Made into fat If energy being used, but no CHO present Starvation Forms ketone bodies (see fat metabolism slides) Danger!
  • 13.
  • 14.
  • 15.
    2. Aconitase ReactionForms isocitrate
  • 16.
    3. Isocitrate DehydrogenaseAll dehydrogenase reactions make NADH or FADH 2
  • 17.
    4. α-ketoglutarate dehydrogenase Same as pyruvate dehydrogenase reaction
  • 18.
    5. Succinyl CoAsynthetase Coupled to synthesis of GTP GTP very similar to ATP and interconverted later
  • 19.
    6. Succinate dehydrogenaseDehydrogenation Uses FAD
  • 20.
    7. Fumarase Additionof water to a double bond
  • 21.
    8. Malate DehydrogenaseMakes NADH Regenerates oxaloacetate for another round
  • 22.
    Net From Kreb’sOxidative process 3 NADH FADH 2 GTP X 2 per glucose 6 NADH 2 FADH 2 2 GTP All ultimately turned into ATP (oxidative phosphorylation)