prof. roshada hashim roshadahashim@gmail
DESCRIPTION
Prof. Roshada Hashim [email protected]. GLYCOLYSIS. General features of Glycolysis Anaerobic degradation of hexose sugar Conversion of a 6-carbon molecule (glucose, fructose) to a 3-carbon molecule ( dihydroxyacetone phosphate, glyceraldehyde 3-phosphate; pyruvate - PowerPoint PPT PresentationTRANSCRIPT
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Prof. Roshada [email protected]
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GLYCOLYSIS
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www.lowcarbluxury.com/newsletter/lclnewsvol03...
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
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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
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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
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Hexokinase is an allosteric enzyme:
Activator: ADPInhibitor: ATP and Glucose 6-Phosphate
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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
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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
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(-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
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www.rpi.edu/.../MBWeb/mb1/part2/gluconeo.htm
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(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 G’ is positive
Step 4: Cleavage of Fructose 1,6bisphosphate to glyceraldehyde 3-P & dihydroxyacetone phosphate
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1. Amino acids participating in the active site: Lys, Cys (thiol grp acts as a base) and His
2. Aldol cleavage
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( 1.8kcal/mol)
1. 2nd glyceraldehyde 3-phosphate formed from this rxn
2. G 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 G for glycolysis is negative)
Step 5: Isomerization of Dihydroxyacetone phosphate to glyceraldehyde 3-P
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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
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2nd phase of glycolysis: production of energy
1. Involves 5 steps
2. Production of ATP
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(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 G’ = -43.1kJ/mol (-10.3kcal/mol) (oxdn) 3-PG to 1,3 bisPG G’ = 49.3kJ/mol ( 11.8kcal/mol) (phosln) Overall G’ = 6.2kJ/mol (1.5kcal/mol)
Step 6: Oxidation of Glyceraldehyde 3-P to 1,3 bisphosphoglycerate
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Oxidation of glyceraldehyde 3-phosphate to a carboxylic acid
EXERGONIC
1
2
3
Electron transfer from G3-P to NAD+
3-phophoglycerate
ENDERGONIC
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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 G’ for the hydrolysisof 1,3bPG = -49.3kJ/mol and the G’ the hydrolysis of ATP is – 30.5kJ/mol, what is the G’ for the formation of 3-phosphoglycerate and ATP?
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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)
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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
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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: G’ =25.1kJ/mol (6kcal/mol)
4. Lactate can be recycled in the liver to form pyruvate and glucose by gluconeogenesis
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www.biologie.uni-hamburg.de/b-online/e19/19d.htm
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Overall conversion of glucose to 2 moles of pyruvate:
G’ = -73.3 kJ/mol (-17.5kcal/mol)
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www.nd.edu/~aseriann/glyreg.html
Regulation of glycolysis
1. Hexokinase
2. Phosphofructokinase
3. Pyruvate kinase
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www-medlib.med.utah.edu/NetBiochem/tabletit.htm
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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
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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 G’ = 61.1kJ/mol(-14.6 kcal/mol)
% of energy conserved is 61.1/184.5 x 100 = 33.1%