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Integration of Metabolism

Integration of Metabolism. Biosynthetic and degradative pathways are almost always distinct. * NADPH is major electron donor in reductive biosynthesis. * ATP is the universal currency of energy. * Biomolecules are constructed from a small set of building blocks. Glycolysis

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Integration of Metabolism

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  1. Integration of Metabolism

  2. Biosynthetic and degradative pathways are almost always distinct. * NADPH is major electron donor in reductive biosynthesis * ATP is the universal currency of energy * Biomolecules are constructed from a small set of building blocks

  3. Glycolysis Pentose phosphate pathway Fatty acids synthesis TCA cycle, Oxidative phosphorylation b-oxidation of Fatty acids Ketone body formation Gluconeogenesis Urea synthesis Compartmentalization of the Major Pathway of Metabolism Communications between different compartments are achieved by a number of carriers to carry metabolic intermediates across membranes. Synthesis and degradation pathways almost always separated Compartmentalization

  4. Interrelationship of macromolecules metabolism

  5. Our bodies are an integrated system not only in case of metabolism pathways but also of organs, each with its own requirements for nourishment and energy utilization. • In spite of this, our tissues share a common circulation system.

  6. Glycolysis, an overall equation • Glycolysis is a 10-step pathway which converts glucose to 2 pyruvate molecules. The overall Glycolysis step can be written as a net equation:Glucose + 2xADP + 2xNAD+ -> 2xPyruvate + 2xATP + 2xNADH

  7. Stage 1 Stage 2

  8. Glycolysis consists from two main phases. • First phase, energy investment. During this step 2xATP are converted to 2xADP molecules. • Second phase, energy generation. During this step 4xADP are converted to 2xATP molecules and 2xNAD+ are converted to 2xNADH molecules.

  9. Glycolysis step 2:Isomerization of glucose-6-phosphate catalysed by Phosphoglucoisomerase:α-D-Glucose-6-phosphate <=> D-Fructose-6-phosphateδGo = +1.7 kJ/mol. Glycolysis step 3:Second phosphorylation catalysed by Phosphofructokinase:D-Fructose-6-phosphate + ATP -> D-Fructose-1,6-bisphosphate + ADP + H+δGo = -18.5 kJ/mol. Glycolysis step 3:Second phosphorylation catalysed by Phosphofructokinase:D-Fructose-6-phosphate + ATP -> D-Fructose-1,6-bisphosphate + ADP + H+δGo = -18.5 kJ/mol

  10. Glycolysis step 4:Cleavage to two Triose phosphates catalysed by Aldolase:D-Fructose-1,6-bisphosphate <=> Dihydroxyacetone phosphate + D-glyceroaldehyde-3-phosphateδGo = +28 kJ/mol Glycolysis step 5:Isomerization of dihydroxyacetone phosphate catalysed by Triose phosphate isomerase:Dihydroxyacetone phosphate <=> D-glyceroaldehyde-3-phosphateδGo = +7.6 kJ/mol

  11. Glycolysis: Energy generation phase Glycolysis step 6:Generation of 1,3-Bisphosphoglycerate catalysed by Glyceraldehyde-3-phosphate dehydrogenase:D-glyceroaldehyde-3-phosphate + NAD+ +Pi <=> 1,3-Bisphosphoglycerate + NADH + H+δGo = +6.3 kJ/mol Glycolysis step 7:Substrate-level phosphorylation, 3-Phosphoglycerate catalysed by Phosphoglycerate kinase:1,3-Bisphosphoglycerate + ADP <=> 3-Phosphoglycerate + ATPδGo = -18.8 kJ/mol

  12. Glycolysis step 8:Phosphate transfer to 2-Phosphoglycerate catalysed by Phosphoglycerate mutase:3-Phosphoglycerate <=> 2-PhosphoglycerateδGo = +4.4 kJ/mol Glycolysis step 9:Synthesis of Phosphoenolpyruvate catalysed by Enolase:2-Phosphoglycerate <=> Phosphoenolpyruvate + H2OδGo = +1.7 kJ/mol Glycolysis step 10:Substrate-level phosphorylation. Pyruvate synthesis catalysed by Pyruvate kinase:Phosphoenolpyruvate + H+ + ADP -> Pyruvate + ATPδGo = -31.4 kJ/mol

  13. e.g: Energy of palmitoyl ~Co A oxidation • Number of cycles= n/2 -1 = 7 cycles • Number of acetyl ~Co A = n/2 =8 So, 7 NADH, each provide 3 ATP when oxidized in the ETC 7X3=21 ATP 7 FADH2 each provide 2 ATP when oxidized in the ETC 7x 2=14 ATP 8 acetyl ~Co A , each provides 12 ATP when converted to CO2& H2O by the TCA cycle 8x12= 96 ATP So total energy yield of oxidation of palmitoyl ~Co A =131 ATP

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