Glycolysis (in depth Biochem) PDF

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Monday, 25 November 2019

Metabolism Glycolysis! The glycoyic pathway is common to nearly all cells, in both prokaryotic cells and eukaryotic cells. The pathway is basically split into two steps, the first is the preparation of the glucose molecule, and hence requires energy investment, but then the second part is the energy payoff phase. ! Glucose will enter the cell via specialised glucose transporters, two good examples of this are GLUT1 and GLUT3. These are present in nearly all mammalian cells and are responsible for the basal glucose uptake.! The process starts with the Glucose being trapped in the cell by Hexokinase, this is carried out due to the fact that Hexokinase converts Glucose into Glucose-6-phosphate. The negatively charged phosphate group ensures that the glucose molecule will not be able to leave the cell. This is due to the fact it is not a substrate the transporters are able to transport. The addition of the phosphate group also helps to destabilise the glucose molecule. ! This helps to facilitate its later metabolism. The carbons are then shuffled round form G-6P by phosphoglucose isomerase, this converts the molecule into fructose 6phosphate. This occurs as the aldose sugar glucose is converted into a ketose sugar. The enzyme has to open the six membered ring and then promote the formation of the fructose sugar. ! Once this is completed a second phosphorylation phase takes place, this is done to make the energy required to split up the glucose molecule as low as possible, the electrostatic repulsions from the two phosphate groups helps this. The phosphofructokinase enzyme is used a large amount in the regulation of blood glucose in the body. This leads to the formation of fructose 1,6-bisphosphate!

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Monday, 25 November 2019 The next stage involves the cleavage of the molecule to form 2 three carbon fragments that both will lead to the formation of 2 pyruvate for use in further metabolic reactions. However, this leads to the formation of 2 differing molecules, GAP and DHAP, however the DHAP is later converted into GAP by triose phosphate isomerase. ! Whilst the reaction is reversible and 96% at equilibrium will be DHAP all the GAP is is removed so quickly by the further stages of glycolysis this does not lead to complications metabolically. ! Now begins the energy payback stage. This begins with another phosphorylation, however this time the source is not ATP but instead an inorganic phosphate. This step is the conversion of GAP to 1,3-bisphosphateglycerate (1,3-BPG).! 1,3-BPG is a acyl phosphate which is a mixed anhydride of phosphoric acid and a carboxylic acid. This class of compounds have very high phosphoryl-transfer potential and hence the next stage occurs easier. The reaction utilises the use of an intermediate as whilst the first part of the reaction is very feasible ΔG -50 kJmol-1 the second part is of the same magnitude of delta G but in the opposite order of magnitude. Therefore the intermediate means the energy profile is as seen adjacent. ! The overall reaction pathway is shown here, this is where one of the ATP molecules we put in is recuperated. ADP is converted here to ATP. The phosphorly-transfer potential is higher than ATP and hence it is used to synthesise it. ! The remains steps of glycolysis are more simple, The first step catalysed by phosphoglycerate mutase is a simple rearrangement where 3phopshoglycerate is converted into 2-phosphoglycerate. The next step is a dehydration catalysed by enolase which converts 2-phosphoglycerate into 2phosphenolpyruvate. Finally the last payoff stage as well as the final step within glycolysis 2-phosphophenolpyruvate is converted into pyruvate by pyruvate kinase. The reason that this can happen is that the Phosphorly form of pyruvate keeps it as an enol, and when the Phosphate is lost it can form its stable ketone form

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