Download Lecture 17 Glycolysis (continued) Recap Phases: priming: glucose

Lecture 17
Glycolysis (continued)
Recap Phases:
priming:
glucose → G-6-P → F-6-P → F-1,6-bisP → DHAP + G-3-P
ATP → ADP
ATP → ADP
DHAP → G-3-P
payoff: 5 reactions (note 2 G-3-P substrates per glucose)
NAD+ → NADH
G-3-P + Pi → 1,3-bisPGA → 3-PGA →
ADP → ATP
Payoff reactions:
2-PGA → PEP →
ADP →
Pyruvate
ATP
Reaction 6
ΔGo’ =+6.3 kJ/mol
ΔG’ = -1.29 kJ/mol
Near equilibrium:
not regulated
Note that the acid C
is oxidized (from aldehyde
to acid)
Reaction 7
ΔGo’ =-18.9 kJ/mol
ΔG’ = +0.1 kJ/mol
Near equilibrium:
not regulated
Note “substrate level
phosphorylation” of ADP
Reaction 8
ΔGo’ =+4.4 kJ/mol
ΔG’ = +0.83 kJ/mol
Near equilibrium:
not regulated
Reaction 9
ΔGo’ =+1.8 kJ/mol
ΔG’ = +1.1 kJ/mol
Near equilibrium:
not regulated
Reaction 10
ΔGo’ =-31.4 kJ/mol
ΔG’ = -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,
substrate of citric acid cycle), alanine (transamination analog of pyruvate)
Summary:
glucose + 2 ADP + 2 Pi + 2 NAD+ → 2 pyruvate + 2 ATP + 2 H2O + 2 NADH + 2 H+
Anaerobic reactions
Without O2, it is essential to reoxidize NADH with products of the glycolysis pathway
In animals, pyruvate + NADH + H+ → lactate + NAD+
In plants and fungi, pyruvate → CO2 +
Also, in plants, pyruvate + CO2 →
acetaldehyde →
ethanol
NADH + H+ → NAD+
OAA
→ malate
NADH + H+ → NAD+
Energy efficiency
glucose → 2 lactate
2 ADP → 2 ATP
ΔGo’ = -196 kJ/mol
ΔGo’ = + 61 (31%)
glucose → 2 ethanol + 2 CO2
2 ADP → 2 ATP
ΔGo’ =-235 kJ/mol
ΔGo’ = + 61 (26%)
But relative to complete oxidation of glucose:
glucose + 6 O2 → 6 CO2 + 6 H2O ΔGo’ = -2840 kJ/mol
glucose → 2 ethanol + 2 CO2 is 61/2840 = 2.1%
glucose → 2 lactate: lactate from muscles recycled in the liver
Control of the rate of glycolysis
Note ATP inhibition, glycogen storage at rest; AMP, FBP stimulation at need
Cancer cells produce most ATP by glycolysis (Warburg effect)
“Why do proliferating cells switch to a less efficient metabolism?” (see Science 324:1029
May 22, 2009)
probable answer: growth requires more C-compounds and reduction power (NADPH),
intermediates of respiration, than ATP energy
Also see:
“Understanding the Warburg effect: the metabolic requirements of cell proliferation.”
(Science 324:1029, 22 May 2009)
“Evidence for an alternative glycolytic pathway in rapidly proliferating cells.” (Science
329:1492, 17 Sept 2010)
“Warburg effect and redox balance”. (Science 334:1219, 2 Dec 2011)
Other compounds enter glycolysis
Galactose → gal-1-P → UDP-gal → UDP-glucose → glucose-1-P → glucose-6-P
Mannose → mannose-6-P → fructose-6-P
fructose → fructose-1-P → DHAP + glyceraldehyde;
glyceraldehyde + ATP → G-3-P + ADP
glycerol + ATP → glycerol-3-P
glycerol-3-P + NAD+ → DHAP
Summary
Glucose is metabolized in a series of 10 reactions to pyruvate
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