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General features of Glycolysis
1. Anaerobic degradation of hexose sugar
2. Conversion of a 6-carbon molecule (glucose, fructose) to a 3-carbon molecule ( dihydroxyacetone phosphate, glyceraldehyde 3-phosphate; pyruvate
3. One 6-carbon molecule will give two 3-carbon molecules
4. All the intermediates are phosphorylated; -vely charged at pH 7
5. Pi bonded by either an ester or anhydride bond
6. 2 phases: activation phase and energy production phase
1. 10 steps in glycolysis2. First 5 steps is the preparation or activation of glucose3. Uses 2 molecules of ATP4. 6-carbon degraded to 2 3-carbon molecules
1. Step 1: Phosphorylation. Glucose converted to glucose 6 phosphate
1. Coupling reaction Glucose Glucose 6-P G°’ = 13.8kJ/mol (3.3kcal/mol) ATP + H2O ADP + Pi G°’ = -30.5kJ/mol (-7.3kcal/mol)
Glucose + ATP Glucose 6-P +ADP G°’ = -16.7kJ/mol (-4.0kcal/mol)
2. Reaction catalysed by hexokinase (remember kinase – ATP dependent enzyme
3. Substrate can be any hexose sugar (fructose, mannose, glucose)
4. Glucose 6-P inhibits hexokinase
5. Keq for this reaction is high (2000) rxn is reversible but this does not happen in the cell b’coz: a. Hexokinase affinity for glucose and ATP is higher than for ADP and G 6-P. hexokinase tends
to be saturated with glucose and ATP b. Hexokinase is inhibited by G 6-P
Liver glucokinase requires a higher glucose concentration to achieve saturation
Glucokinase: lowers blood glucose
Glucokinase Hexokinase
High activity in the liver
Low activity in the liver
Not found in muscle Found in the muscle
Specific for glucose Hexoses are substrates
Km(glucose) = 10mM Km(glucose) = 0.1
Step 2: Isomerization. Glucose 6 phosphate to fructose 6-phosphate
Glucose 6-P Fructose 6-P G°’ = 1.67kJ/mol (0.4kcal/mol)
1. The enzyme that catalyses the reaction is glucose phosphate isomerase2. Acid-base catalysis: Lys and His in the active site: Lys acts as the acid and His as the
base
(-3.4 kcal/mol)1. Endergonic reaction of phosphorylation of fructose 6-P is coupled with the
hydrolysis of ATP. 2nd ATP; 2nd activation step
2. This is the step which commits glucose to glycolysis (G 6-P and F 6-P involved in other pathways. The only way for F 1,6 bisP to be metabolised is via glycolysis
3. Highly exergonic & irreversible
4. PFK – key regulatory enzyme in glycolysis; ALLOSTERIC ENZYME
5. ATP: negative modulator
Step 3: Phosphorylation of fructose 6-phosphate to Fructose 1,6bisphosphate
(5.7 kcal/mol)
1. The last of the activations step
2. Cleavage takes place between carbon-3 and carbon-4
3. Rxn moves towards triose sugar formation although ΔG°’ is positive
Step 4: Cleavage of Fructose 1,6bisphosphate to glyceraldehyde 3-P & dihydroxyacetone phosphate
1. Amino acids participating in the active site: Lys, Cys (thiol grp acts as a base) and His
2. Aldol cleavage
( 1.8kcal/mol)
1. 2nd glyceraldehyde 3-phosphate formed from this rxn
2. ΔG under physiological conditions is slightly positive: 2.41kJ/mol or 0.58kcal/mol
3. Reaction favours formation of glyeraldehyde 3-phosphate because G for subsequent reactions in glycolysis are very negative and drives the rxn forward. (Overall ΔG for glycolysis is negative)
Step 5: Isomerization of Dihydroxyacetone phosphate to glyceraldehyde 3-P
courses.cm.utexas.edu/.../Lecture-Ch14-1.html
glucose C1 and C6 becomes glyceraldehyde 3-phosphate C3
glucose C2 and C5 becomes glyceraldehyde 3-phosphate C2
glucose C3 and C4 becomes glyceraldehyde 3-phosphate C1
(1.5kcal/mol)
1. Involves 2 sets of reactions: i) Electron transfer rxn, from Glyceraldehyde 3-P to NAD+
ii) The addition of a phosphate
2. G 3-P to 3-Phosphoglycerate ΔG°’= -43.1kJ/mol (-10.3kcal/mol) (oxdn) 3-PG to 1,3 bisPG ΔG°’ = 49.3kJ/mol ( 11.8kcal/mol) (phosln) Overall ΔG°’= 6.2kJ/mol (1.5kcal/mol)
Step 6: Oxidation of Glyceraldehyde 3-P to 1,3 bisphosphoglycerate
Oxidation of glyceraldehyde 3-phosphate to a carboxylic acid
EXERGONIC
1
2
3
Electron transfer from G3-P to NAD+
3-phophoglycerate
ENDERGONIC
Step 7: Conversion of 1,3 bisphosphoglycerate to 3-phosphoglycerate
(-4.5kcal/mol)
1. A phosphate grp is transferred frm 1,3bPG to ADP
2. First ATP formed in glycolysis
3. Substrate-level phosphorylation
Question:If the ΔG°’for the hydrolysisof 1,3bPG = -49.3kJ/mol and the ΔG°’the hydrolysis of ATP is – 30.5kJ/mol, what is the ΔG°’for the formation of 3-phosphoglycerate and ATP?
Step 8: Conversion of 3-PG to 2-PG
(1.1 kcal/mol)
Step 9: Dehydration of 2-PG to phosphoenolpyruvate (PEP)
(0.4 kcal/mol)
Step 10: Transfer of phosphate grp. from phosphoenolpyruvate (PEP) to ADP
(-7.5 kcal/mol)
1. PEP high energy compd. with high phosphate-grp transfer potential
2. Another example of substrate level phosphorylation
3. Pyruvate kinase is an allosteric enzyme
4. Pyruvate kinase is inhibited by high levels of ATP
Conversion of pyruvate to lactate in the muscle
1. Rxn is catalysed by lactate dehydrogenase
2. NAD+ is the co-factor
3. Rxn highly exergonic: ΔG°’=25.1kJ/mol (6kcal/mol)
4. Lactate can be recycled in the liver to form pyruvate and glucose by gluconeogenesis
www.nd.edu/~aseriann/glyreg.html
Regulation of glycolysis
1. Hexokinase
2. Phosphofructokinase
3. Pyruvate kinase
Substrate To ATP
Glucose Glucose 6-phosphate -1
Fructose 6-phosphate Fructose 1,6 bisphosphate -1
2 x 1,3 phophoglycerate 2 x 3-phosphoglycerate +2
2 x PEP 2 x pyruvate +2
Net 2
ATP production and Efficiency of Glycolysis
Glucose + 2 ADP + 2Pi 2 Lactate + 2 ATP G’ = -184.5kJ/mol(-44.1 kcal/mol)
But in glycolysis only 2 ATPs are formed when glucose is oxidised to lactate. To form the ATP molecules would require : 161.1kJ/mol(-14.6 kcal/mol)
2ADP + 2Pi 2ATP ΔG°’= 61.1kJ/mol(-14.6 kcal/mol)
% of energy conserved is 61.1/184.5 x 100 = 33.1%
Conversion of pyruvate to lactate in the muscle
1. Rxn is catalysed by lactate dehydrogenase
2. NAD+ is the co-factor
3. Rxn highly exergonic: ΔG°’=25.1kJ/mol (6kcal/mol)
4. Lactate can be recycled in the liver to form pyruvate and glucose by gluconeogenesis
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