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BC21D: Bioenergetics & Metabolism

BC21D: Bioenergetics & Metabolism. The formation of Acetyl Coenzyme A; Krebs cycle; electron transport chains and chemiosmotic phosphorylation mechanism:. andrew.pearson@uwimona.edu.jm. FAD NAD +. FADH 2 NADH. The formation of Acetyl Coenzyme A. BC21D: Bioenergetics & Metabolism.

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BC21D: Bioenergetics & Metabolism

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  1. BC21D: Bioenergetics & Metabolism The formation of Acetyl Coenzyme A; Krebs cycle; electron transport chains and chemiosmotic phosphorylation mechanism: andrew.pearson@uwimona.edu.jm

  2. FAD NAD+ FADH2 NADH

  3. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism Pyruvate and acetyl CoA are important metabolites at the intersection of many carbon-metabolising pathways.

  4. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism Pyruvate and acetyl CoA are important metabolites at the intersection of many carbon-metabolising pathways.

  5. Metabolic relationship between carbohydrate and fat catabolism Pyruvate Carboxylase Pyruvate Dehydrogenase Complex Some amino acids

  6. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism 1. Glycolysis by either the EMP pathway, or variants such as PPP/HMP.

  7. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism Recall that PK is an important regulatory enzyme in some cells.

  8. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism 2. Aerobic oxidation of lactate, e.g. by heart or liver isoenzymes of Lactate dh.

  9. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism 3. Oxidative deamination of alanine, e.g. by liver after release from skeletal muscle during fasting.

  10. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism Lets us now look at pyruvate dehydrogenase

  11. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism

  12. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism

  13. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism

  14. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism pdh reaction mechanism E1 = Pyruvate dehydrogenase E2 = Dihydrolipoyl transacetylase E3 = Dihydrolipoyl dehydrogenase

  15. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism Pdh is regulated by reversible, inhibitory phosphorylation of E1.

  16. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism Pdh is regulated by 4 reversible, inhibitory kinases of E1. The kinases have differing tissue specificities. The kinases are activated by increasing the ratios of: [NADH]/[NAD]; [acetyl CoA]/[CoA]; [ATP]/[ADP] The kinases are inhibited by pyruvate. Insulin stimulates dephosphorylyation.

  17. Regulation of the Pyruvate Dehydrogenase Complex Pyruvate dehydrogenase phosphatase “Pyruvate dehydrogenase kinase”, actually…. Pyruvate dehydrogenase complex Pyruvate dehydrogenase kinases 1 – 4, with different tissue specificities Phosphorylation sites on Pdh subunit E1

  18. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism Apart from carbohydrates, carbons from other molecules can form acetyl CoA. CHO

  19. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism Parts of leucine isoleucine tryptophan are degraded to acetyl CoA

  20. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism Lets us now look at fatty acid degradation

  21. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism

  22. Figure 3 Modulation of CPT I activity by carbohydrates The pathway shown in red is the established pathway for the inhibition of hepatic CPT activity by carbohydrates. The other pathways shown are alternative routes that may be operative in heart Abbreviations : CPT, carnitine palmitoyl transferase ; CAT, carnitine acetyl transferase. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism

  23. The formation of Acetyl Coenzyme A BC21D: Bioenergetics & Metabolism Just to remind you where we are going with this!

  24. The major metabolic role of the Krebs cycle in most aerobes is the oxidative degradation of acetate to two molecules of CO2 and some high energy reducing equivalents.

  25. BC21D: Bioenergetics &Metabolism The Krebs cycle

  26. BC21D: Bioenergetics & Metabolism This is control point in some bacteria: the Krebs cycle is not partitioned from the cytosol. ATP is a negative modulator, raising the enzyme’s Km value for acetyl CoA Citrate synthase

  27. BC21D: Bioenergetics & Metabolism Aconitase Aconitase contains an iron-sulphur centre Aconitate is not normally released from the enzyme Aconitase

  28. BC21D: Bioenergetics & Metabolism This is one of the control points of the Krebs cycle. It is an allosteric enzyme: ADP is the positive modulator enhancing the binding of isocitrate and NAD+. NADH is a competitive inhibitor of NAD+ binding. ATP also inhibits. NAD+ Isocitrate dehydrogenase NADH + H+

  29. Another control point of the Krebs cycle BC21D: Bioenergetics & Metabolism NAD+ α-ketoglutarate dehydrogenase complex NADH + H+

  30. BC21D: Bioenergetics & Metabolism (a) animal α-KG dh is very sensitive to ADP, Pi, and Ca2+; (b) these positive effectors increase the affinity of α-KG dh to α-ketoglutarate; (c) α-KG dh is inhibited by ATP, NADH, and succinyl-CoA; (d) the ATP effect is realized mainly via opposition to ADP activation; (e) NADH, in addition to inhibiting the dihydrolipoamide dehydrogenase component of the enzyme complex (competitively versus NAD+), decreases the affinity of α-ketoglutarate dehydrogenase to its substrate; (f) bacterial and plant α-KG dh are activated by AMP instead of ADP. These main effects form the basis of short term regulation of α-KG dh.

  31. BC21D: Bioenergetics & Metabolism Succinate thiokinase GTP GDP + Pi

  32. BC21D: Bioenergetics & Metabolism Succinate dehydrogenase complex FADH2

  33. BC21D: Bioenergetics & Metabolism NADH + H+ Malate dehydrogenase

  34. BC21D: Bioenergetics & Metabolism Amino acids can feed their carbons into the Krebs cycle for gluconeogenesis. Recall when and in which cells this occurs.

  35. Amino acids with direct linkages to the Krebs cycle are especially important. BC21D: Bioenergetics &Metabolism

  36. BC21D: Bioenergetics &Metabolism Possible metabolic outputs from the Krebs cycle From Nelson & Cox

  37. BC21D: Bioenergetics & Metabolism From Stryer

  38. BC21D: Bioenergetics &Metabolism Anaerobes lacking α-KG dh therefore have an incomplete Krebs cycle.

  39. BC21D: Bioenergetics &Metabolism Some plants, invertebrates and fungi have the glyoxylate cycle for converting two acetates into succinate, thus are able to use fatty acids for gluconeogenesis.

  40. BC21D: Bioenergetics &Metabolism

  41. BC21D: Bioenergetics & Metabolism electron transport & bioenergetics

  42. BC21D: Bioenergetics & Metabolism electron transport & bioenergetics

  43. BC21D: Bioenergetics & Metabolism electron transport & bioenergetics Collecting light energy from the solar (or an artificial) source is a major alternative to carbon catabolism.

  44. BC21D: Bioenergetics & Metabolism electron transport & bioenergetics Recall this image from last year. It highlights the similarities between different energy metabolisms.

  45. BC21D: Bioenergetics & Metabolism electron transport & bioenergetics

  46. BC21D: Bioenergetics & Metabolism electron transport & bioenergetics

  47. BC21D: Bioenergetics & Metabolism electron transport & bioenergetics

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