GLYCOLYSIS
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Transcript of GLYCOLYSIS
GLYCOLYSIS
Glycolysis: oxidative breakdown of glucose to pyruvate with capture of some energy as ATP, NADH (first step in respiration) Themes:
• sequenti , al simple enzymatic reactions • investm ent of energy; then recapture • control of pathway at key step :s <G <0 • production of useful intermediates
Glycolysis Subsequent reactions glucose pyruvate lactate (or) CO2+ethanol (or)
malate
CO2 + H2O --
Compare respiration to combustion: C6H12O6 + 6 O2 6 CO2 + 6 H2O
G ’o = -2840 k /J mol In respiratio ,n including glycolysis, som e G ’o
(~ 35%) is retained in formation of ATP
O2 absent
O2 present
Glycolysis can be divided into two phases: priming and payoff
Phase 1: five priming reactions
1. glucose + ATP G-6-P + ADP
2. G-6-P F-6-P
3. F-6-P + ATP F-1,6-bisP + ADP
4. F-1,6,bisP DHAP + G-3-P
5. DHAP G-3-P
Glycolysis can be divided into two phases: priming and payoff
Phase 2: five payoff reactions
6. G-3-P + PI + NAD+ 1,3-bisPGA + NADH
7. 1,3-bisPGA + ADP 3-PGA + ATP
8. 3-PGA 2-PGA
9. 2-PGA PEP
10. PEP + ADP pyruvate + ATP
Reaction 1 • kinase: adds Pi using ATP
as donor • Note the need for Mg2+
with ATP (comm )on • G ’o =+13.8 /kJmol = -30.5 -16.7 ’ =G G ’o + RT [ ]/[ ]ln P R = -33 .9 • Reactions with <<0G can
be regulat :ed • Hexokinase is allosterically
inhibited b yG-6- , P Km ~ 0.1 m M ([gluco ]se in bl ~ood 4 mM)
• Glucokinase in liver not allostericall y inhibited: Km ~ 10 mM
• Phosphorylat ion of glucose traps it in the cell
Reaction 2 • isomera : se catalyzes the
structural rearrangement of isomers (aldose
ketose)
• Go’ =+1.67 kJ/mol G’ = -2.92 kJ/mol
• Near equilibrium:
not regulated
Reaction 3 • G ’o =+16.3 /kJmol = -30.5 -14.2
’ = G -18.89 • Regulated • ATP is an alloster ic inhibitor
AMP reverses AT P inhibition (ATP down 8% resu lts in
AMP up 4-fo )ld
Reaction 4 Equilibrium:
Go’ =+23.8 kJ/mol G’ = -0.23 kJ/mol
Reaction 5 Equilibrium:
Go’ =+7.56 kJ/mol G’ = +2.41 kJ/mol
Another isomerase: ketose aldose
Reaction 6
Go’ =+6.3 kJ/mol G’ = -1.29 kJ/mol
Near equilibrium:not regulated
Note that the C in-C-O-PO3 has beenoxidized (from aldehydeto acid)
The coupling of acyl-phosphate formation to oxidation avoidsan energy hump that would drastically slow the reaction.
Reaction 7
Go’ =-18.9 kJ/mol G’ = +0.1 kJ/mol
Near equilibrium: not regulated Note “substrate level phosphorylation” of ADP (but enzyme named for the back reaction)
Reaction 8 mutase: an enzyme that catalyzes the shifting of a functional group from one position to another within the same molecule
Go’ =+4.4 kJ/mol G’ = +0.83 kJ/mol
Near equilibrium: not regulated
Reaction 9
Go’ =+1.8 kJ/mol G’ = +1.1 kJ/mol
Near equilibrium: not regulated
Reaction 10
Go’ =-31.4 kJ/mol G’ = -23.0 kJ/mol
Not near equilibrium, so controllable: activated by AMP, fructose-1,6-bisP; inhibited by ATP (product of this reaction), acetyl-CoA (product of a following reaction and substrate of citric acid cycle), alanine (trans- amination analog of pyruvate)
Summary of glycolysis: glucose + 2 ADP + 2 Pi + 2 NAD+ 2 pyruvate + 2 ATP + 2 H2O + 2 NADH + 2 H+
What happens next? It depends on the environment: aerobic or anaerobic. Regeneration of NAD+ is essential to keep the process going.
including oxidationof NADH
In fungi and plants in the absence of O2, pyruvate is decarboxylated to acetaldehyde; acetaldehyde is reduced to ethanol; NADH is oxidized to NAD+.
The NAD+ is recycled to oxidize more glyceraldehyde-3-P.
In animals and some bacteria, pyruvate is reduced to lactate asNADH is oxidized to NAD+.
Energy efficiency glucose 2 lactate Go’ = -196 kJ/mol 2 ADP 2 ATP Go’ = + 61 (31%) glucose 2 ethanol + 2 CO2 Go’ = -235 kJ/mol 2 ADP 2 ATP Go’ = + 61 (26%)
Control: activity of glycolysis depends on allosteric enzymes andresponds to energy requirement.
In muscle:
Control: activity of glycolysis depends on allosteric enzymes andresponds to energy requirement.
In liver, fructose-2,6-bisP is a important stimulator of PFK:
enhances substrate activation relieves allosteric inhibition
Cancer cells produce most of their ATP by glycolysis (Warburg effect) Why do proliferating cells switch to a less efficient metabolism? Probable answer: growth requires more C-compounds and reduction power (NADPH), than ATP energy. (see Science 324:1029 May 22, 2009)
Summary
•Glucose is metabolized to pyruvate in a series of 10 reactions.
•Glycolysis provides the cell (cytoplasm) with 2 mol ATP/glucose.
•Glycolysis also provides cytoplasm with 2 mol NADH/glucose.
•In the absence of O2, NADH is oxidized by reduction of pyruvate.
•In the presence of O2, NADH is oxidized in the mitochondria.
•Rate of glycolysis is controlled at 3 key allosteric enzymes.