Download BIOENERGETICS AND HIGH

BIOENERGETICS AND
HIGH - ENERGY COMPOUNDS
Tomáš Kučera
[email protected]
Department of Medical Chemistry and Clinical Biochemistry
2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital
2016
BIOENERGETICS
how organisms
gain,
convert,
store
and utilize
energy
GIBBS
FREE ENERGY
G = H − TS ⇒ ∆G = ∆H − T∆S = Qp − T∆S
G decrease in a biological process represents its
maximum recoverable work.
equilibrium: ∆G = 0
spontaneous (exergonic) process: ∆G < 0 (it can do work)
endergonic process: ∆G > 0
GIBBS
FREE ENERGY
one of the thermodynamic potentials
no rate information – it is given by the mechanism
a process’ (non-)possibility given only by the initial and final
states
a catalyst (enzyme) can only accelerate equilibrium
attainment, not change its state
⇒ coupling is possible
depends on temperature: equilibrium: T =
∆H
∆S
∆G = ∆H − T∆S
−
+
−
−
+
+
+
−
Both enthalpically favored (exothermic) and entropically favored. Spontaneous (exergonic) at all temperatures.
Enthalpically favored but entropically opposed. Spontaneous
only at temperatures below T = ∆H
.
∆S
Enthalpically opposed (endothermic) but entropically favored. Spontaneous only at temperatures above T = ∆H
.
∆S
Both
enthalpically
and
entropically
opposed.
Unspontaneous (endergonic) at all temperatures.
∆H
∆S
CHEMICAL
EQUILIBRIA
THE REACTION
aA + bB
cC + dD
∆G = ∆G0 + RT ln
[C]c [D]d
[A]a [B]b
(∆G0 = standard G change of the reaction)
constant term — depends only on the reaction
variable term — depends on temperature and
concentrations of reactants and products
EQUILIBRIUM
∆G = 0
⇓
∆G0 = −RT ln Keq
Keq =
[C]c [D]d
[A]a [B]b
∆G0 and Keq directly related
10 -fold change in Keq changes ∆G0 by 5.7 kJ mol−1
=e
−∆G0
RT
ENERGY CHANGES
X
∆G0f (products) −
X
∆G0f (reactants)
∆G0f = ∆G0 of formation
zdroj
∆G0 =
zdroj
FREE
FREE
ENERGY CHANGES
standard state
activity 1 mol l−1
25 ◦C
1 bar
biochemical standard state
water activity = 1
pH = 7
substances undergoing acidobasic dissociation:
c = total c of all species at pH = 7
COUPLED
REACTIONS
A + B
D + E
A + B + E
GLUCOSE
C + D
F + G
C + F + G
∆G1
∆G2
∆G3 = ∆G1 + ∆G2
PHOSPHORYLATION
endergonic reaction:
glucose + P
glucose-6- P + H2 O
∆G00 = 13.8 kJ mol−1
exergonic reaction:
ATP + H2 O
ADP + P
∆G00 = −30.5 kJ mol−1
coupled reaction:
glucose + ATP
glucose-6- P + ADP ∆G00 = −16.7 kJ mol−1
REDOX
POTENTIAL
also oxidation-reduction (reduction) potential
expresses the substance’s readiness to accept electrons
ox + n · e−
(half-cell)
red
n+
n+
Aox + Bred
Ared + Box
NERNST
EQUATION
∆G = ∆G0 + RT ln
[Ared ][Bn+
ox ]
[An+
ox ][Bred ]
∆G = −nF ∆E
0
E=E −
RT
nF
· ln
[red]
[ox]
0
⇒ ∆E = ∆E −
RT
nF
· ln
[Ared ][Bn+
ox ]
[An+
ox ][Bred ]
REDOX
POTENTIAL
ΔG0´
E0´(V)
-0,60 – values higher
-0,42 (reductant)
isocitrate
glutathione-SH
NADH + H+
glyceraldehyde-3-phosphate + H3PO4
FADH2
lactate
malate
cytochrome b (Fe2+)
succinate
dihydroubiquinone
cytochrome c (Fe2+)
H2O2
H2O
2-oxoglutarate + CO2
glutathione-SS
NAD+
1,3-bisphosphoglycerate
FAD
pyruvate
oxalacetate
cytochrome b (Fe3+)
fumarate
ubiquinone
cytochrome c (Fe3+)
O2
½ O2
-0,38
-0,34
-0,32
-0,28
-0,20
-0,19
+ne– –ne–
-0,17
0,00
+0,03
+0,10
+0,26
+0,29 + values
+0,82 (oxidant) lower
zdroj
Oxidized form
acetate
2H+
exergonic reaction
Reduced form
acetaldehyde
H2
endergonic reaction
E as an energy scale
REDOX
POTENTIAL
E0 = 0 V for standard hydrogen half-reaction (electrode)
H+ at pH 0, 25 ◦C, 1 bar in equilibrium with Pt-black
electrode saturated with H2
pH = 7 ⇒ E00 = −0.421V
HIGH-ENERGY
COMPOUNDS
hydrolyzed to drive endergonic reactions
contain “high-energy bond”
zdroj
ATP
a central role (universal “energy currency” of the cell)
3 phosphoryl groups bound by one phosphoester and
two phosphoanhydride bonds
ATP
R1 O
P + R2 OH
R1 OH + R2 O
P
phosphoryl transfer reaction – enormous metabolic
significance
ATP + H2 O
ATP + H2 O
P P + H2 O
ADP + P
AMP + P
2P
∆G0 = −30.5 kJ mol−1
P ∆G0 = −45.6 kJ mol−1
∆G0 = −19 kJ mol−1
kinetic stability,
thermodynamic instability
(high −∆G0 )
cell energy charge (usually 0.8–0.95)
[ATP] + 12 [ADP]
[ATP] + [ADP] + [AMP]
adenylate kinase: ATP + AMP
2 ADP
ATP is formed using more exergonic reactions
COUPLED
A
REACTIONS
∆G00 = 4 kcal mol−1
B
[B]
[A]
= Keq = e
A + ATP + H2 O
Keq =
−∆G0
1,36
= 1.15 · 10−3
B + ADP + P + H+
∆G00 = −3.3 kcal mol−1
[B]
[A]
·
[ADP][ P ]
[ATP]
= 2.67 · 102
at equilibrium:
[B]
[ATP]
= Keq
= 2.67 · 102 · 500 = 1.34 · 105
[A]
[ADP][ P ]
the equilibrium B/A ratio is 108 times higher!
n ATP molecules hydrolyzed ⇒ the ratio is 108n times
higher!
ATP
CONSUMPTION
“low-energy” phosphorylated compounds
NTP interconversions
formation of CTP, GTP, UTP, dATP, dCTP, dGTP, dTTP
nucleoside diphosphate kinase
ATP + NDP
ADP + NTP
processes based on protein conformational changes
protein folding
active transport
movements
ATP
ATP FORMATION
substrate-level phosphorylation
oxidative phosphorylation (photophosphorylation)
adenylate kinase reaction
phosphagens
ATP TURNOVER
average adult resting person
about 3 mol h−1 (1.5 kg h−1 ), i.e. about 40 kg d−1
strenuous activity – up to 0.5 kg min−1
“HIGH-ENERGY
BONDS ”
no high-energy bond exists!
phosphoanhydrides
other anhydrides
phosphosulphates, acylphosphates
carbamoylphosphate
phosphoguanidines (phosphagens – phosphocreatine,
phosphoarginine)
enol phosphates
thioesters
zdroj
zdroj
resonance stabilization
higher solvation energy of the hydrolysis products
electrostatic repulsion
HIGH-ENERGY
COMPOUNDS
zdroj
there are no high-energy compounds as well!
ENERGY
METABOLISM SCHEME
amino acids
fatty acids
alternative
pathways
sugars
glycolysis
β-oxidation
NADH
NAD+
lactate
NADH
NAD+
fermentative
NAD+
regeneration
pyruvate
ethanol
propionate
butyrate
butanol
formate
H2
CO2
acetate
2,3-butandiol
succinate
oxidative
decarboxylation
Calvin cycle
citric acid
cycle
Ac~S–CoA
CO2
ADP
ATP
respiratory
chain
oxidative
phosphorylation
O2
H 2O
NADPH
photosynthetic
electron transport
chain
photophosphorylation
NADP+
hν
ADP
ATP
zdroj
NAD+
NADH
THE END
KONEC
–
THE END
Thank you for your attention!
⇒ coupling is possible
GIBBS
FREE ENERGY
depends on temperature: equilibrium: T =
∆H
∆S
∆G = ∆H − T∆S
−
+
−
−
+
+
+
−
Both enthalpically favored (exothermic) and entropically favored. Spontaneous (exergonic) at all temperatures.
Enthalpically favored but entropically opposed. Spontaneous
only at temperatures below T = ∆H
.
∆S
Enthalpically opposed (endothermic) but entropically favored. Spontaneous only at temperatures above T = ∆H
.
∆S
Both
enthalpically
and
entropically
opposed.
Unspontaneous (endergonic) at all temperatures.
∆
ΔG0´
E0´(V)
-0,60 – values higher
-0,42 (reductant)
isocitrate
2-oxoglutarate + CO2
-0,38
glutathione-SH
NADH + H+
glyceraldehyde-3-phosphate + H3PO4
FADH2
lactate
malate
cytochrome b (Fe2+)
succinate
dihydroubiquinone
cytochrome c (Fe2+)
H2O2
H 2O
glutathione-SS
NAD+
1,3-bisphosphoglycerate
FAD
pyruvate
oxalacetate
cytochrome b (Fe3+)
fumarate
ubiquinone
cytochrome c (Fe3+)
O2
½ O2
-0,34
-0,32
-0,28
-0,20
-0,19
+ne– –ne–
-0,17
0,00
+0,03
+0,10
+0,26
+0,29 + values
+0,82 (oxidant) lower
exergonic reaction
Oxidized form
acetate
2H+
endergonic reaction
Reduced form
acetaldehyde
H2
amino acids
fatty acids
alternative
pathways
sugars
glycolysis
β-oxidation
NADH
NAD+
lactate
NADH
NAD+
fermentative
NAD+
regeneration
pyruvate
ethanol
propionate
butyrate
butanol
formate
H2
CO2
acetate
2,3-butandiol
succinate
oxidative
decarboxylation
Calvin cycle
citric acid
cycle
Ac~S–CoA
CO2
NAD+
NADH
ADP
ATP
respiratory
chain
oxidative
phosphorylation
O2
H 2O
NADPH
photosynthetic
electron transport
chain
photophosphorylation
NADP+
hν
ADP
ATP