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The citric acid cycle and fatty acid oxidation

The citric acid cycle and fatty acid oxidation. Objectives. ,. ,. slides 12-15 later in the lecture. Refer to chapter 17, Stryer 5e. Lecture 21, Michael Schweizer. In eukaryotes acetyl CoA is produced in mitochondria from molecules derived from sugar and fats. See SELF STUDY (lecture 20).

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The citric acid cycle and fatty acid oxidation

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  1. The citric acid cycle and fatty acid oxidation • Objectives , , slides 12-15 later in the lecture. Refer to chapter 17, Stryer 5e Lecture 21, Michael Schweizer

  2. In eukaryotes acetyl CoA is produced in mitochondria from molecules derived from sugar and fats

  3. See SELF STUDY (lecture 20)

  4. Fatty acids are also oxidised to acetyl CoA

  5. EM of a lipid droplet in the cytoplasma and the structure of fats

  6. In the final stages of food molecules, NADH, FADH2 (not shown) produced by the citric acid cycle donate high energy electrons that are used to reduce oxygen gas to water

  7. See next slides

  8. Each turn of the citric acid cycle produces one molecule GTP, one molecule FADH2 and three molecules of NADH+ H+ (not shown!)

  9. Overall equation for the citric acid cycle: CH3CO-S-CoA + 2 H2O + 3 NAD+ + FAD + GDP + Pi 2 CO2 + 3 NADH + 3 H+ + FADH2 + CoA-SH + GTP DGo’ = -9,5 kcal . mol-1 7 [H] 3 [O] But needed 9 [H] 9 [H] 9 [H] 4 [O] 4 [O] PS: If you add up the hydrogen/oxygen atoms, they don’t balance on the two parts of the equation. The reason for this is the shortfall of H2O as explained in the two previous slides. 6 [H] + 2 [H] + 1 [H] 4 [O] Therefore 1 H2O

  10. substrate level phosphorylation H2O

  11. Two molecules of water have been consumed (steps 1 & 7) To account for the net production of only two moles of H2O, a third molecule of H2O must be accounted for. This is done by noting that GTP is produced from GDP and H3PO4 in step 5 of the cycle. This arises from the involvement of H3PO4 in the breakdown of succinyl CoA (step 5) The actual reaction given now can be notionally regarded for balance sheets purposes as equivalent to two reactions: GDP + Pi GTP + H2O succinyl CoA + H2O succinate + CoASH substrate level phosphorylation succinyl CoA + GDP + Pi +H2O succinate + GTP + CoASH + H2O Finally 3 moles of CO2 are produced: only the CO2 produced from the pyruvate oxidation arises directly from pyruvate. The other two have as their origin the two carboxylic acids of oxaloacetate!

  12. Glycolysis and the citric acid cycle provide the precursors needed to synthesise many important biological molecules

  13. Topping up (anaplerotic (Greek origin “fill up”) reaction) the citric acid cycle Biosynthetic roles of the citric acid cycle (see Stryer 5e, p 482) The role of biotin in the active site of enzymes catalysing carboxylation reactions (shown here for pyruvate carboxylase).

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