Integration of Metabolism

* Biomolecules are constructed from a small set of building blocks

* NADPH is major electron donor in reductive biosynthesis

* ATP is the universal currency of energy

Biosynthetic and degradative pathways are almost always distinct.

GlycolysisPentose phosphate pathwayFatty acids synthesis

TCA cycle, Oxidative phosphorylation-oxidation of Fatty acidsKetone body formation

GluconeogenesisUrea synthesis

Communications betweendifferent compartmentsare achieved by a number of carriers to carry metabolic intermediates across membranes.

Compartmentalization of the Major Pathway of Metabolism

Synthesis and degradation pathways almost always separated Compartmentalization

Interrelationship of macromolecules metabolism

• 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.

 

• 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

Stage 1

Stage 2

• Glycolysis consists from two main phases.

• First phaseFirst phase, energy investment. During this step 2xATP are converted to 2xADP molecules.

• Second phaseSecond phase, energy generation. During this step 4xADP are converted to 2xATP molecules and 2xNAD+ are converted to 2xNADH molecules.

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

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

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

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

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