Bioenergetics and Glycolysis Getting the E out of C.
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Transcript of Bioenergetics and Glycolysis Getting the E out of C.
Bioenergetics and Glycolysis
Getting the E out of C
Overall Chemical Reaction
• For all of Cellular Respiration
C6H12O6 + 6 O2 --- 6 CO2 + 6 H2O
Overall free energy = 687 kcal/mol or 3.8 kcal/g
Not really that efficient
(Stay tuned for the actual)
Energy Transfer follows thermodynamic laws
• Gibbs helmholtz
ΔG = ΔH – TΔS• Enthalpy• Entropy
– Remember ΔSuniverse > 0 is a spontaneous process
• Overall if ΔG < 0 the process is spontaneous• ΔG = -RTlnK
– Relates ΔG to equilibrium• ΔG are additive
• State function• Overall ΔG has to be – for a process to be spontaneous
Le Chatelier’s Principle and ΔG
• Remember Le Chatelier and affect on equilibrium– If one reaction has a positive ΔG, but the next
reaction, which is in equilibrium has a negative ΔG , the first reaction can be pulled through
– Many examples of this in glycolysis
ATP (Adenosine Tri-Phosphate)
OH P O
O
O
P OO
O
P O
O
O
N
O
N
N
OH
OH
N
NH2
Hydrolysis of ATP
OH P O
O
O
P OO
O
P O
O
O
N
O
N
N
OH
OH
N
NH2
OH P OO
O
P O
O
O
N
O
N
N
OH
OH
N
NH2
O P O
O
O
+
ATP ------ ADP + Pi + 7.3 kcal
Energy from ATP hydrolysis
• 7.3 kcal /mol (30.5 kJ/mol for you SI nuts)
• Energy from:– Separation of negative charges– Increased entropy
• Phosphate now free…2 things instead of one
– Resonance stabilization of phosphate
Other Energy sources
• Hydrolysis of thioester– Resonance
stabilization of carboxylate
– Energy released from group transfer, not simply hydrolysis
– Coenzyme A (CoA) is an important thiol that forms thioesters
R S
O
R'R
O
O SHR
+
Coenzyme A
OP O
O
OO P O
O
O
P O
O
O
N
O
N
N
OH
N
NH2
CC
CH3
CH3H
OH
CN
O
H
CH2CH2C
O
NCH2CH2
H
SH
from pantothenic acid(Vitamin B5)
from beta alanine
Redox
• Review:– Electron transfer reactions– Energy from electron transfer– Electrons typically transferred to a carrier
• NAD+ + 2 e- + 2H+ - NADH + H+
• FAD + 2 e- + 2H+ - FADH2
• Electrons transferred later for ATP generation
NAD (Nicotinamide Adenine Dinucleotide)
O
P
O
O
O
P
O
O
O
N
O
N
N
OH
OH
N
NH2
N+
OHOH
O
H
NH2
O
Reduction of NAD+ on Nicotinamide Ring
N+
H
NH2
O
R
2 H+2 e -
N
H
NH2
OH
R
H+
NADHNAD
+ ++
FAD (Flavin Adenine Dinucleotide)
CH2
OHOH
OH
N
N
N
NCH3
CH3
O
O
H
CH2
O
OP O
O
ON
O
N
N
OH
OH
N
NH2O P O
Reduction of Flavin Ring on FAD
N
N
N
NCH3
CH3
O
O
H
R
2 H+2 e-
N
N
N
NCH3
CH3
O
O
H
H
H
R
FADFADH2
+ +
Glycolysis
• In Cytosol
• Anaerobic
• Breakdown of glucose to two pyruvate molecules
– Glucose + 2 ADP + 2 Pi + 2 NAD+ - 2 pyruvate + 2 ATP + 2 NADH + 2 H+
– C6H12O6 + 2 ADP + 2 Pi + 2 NAD+ - 2 C3H3O3- + 2 ATP + 2 NADH + 2 H+
GlycolysisO
OHOH
OH
OH
CH2OH
glucose
ATP ADP
O
OHOH
OH
OH
CH2OP
Glucose-6-phosphate
hexokinasehexose phosphate isomerase
O
CH2OPCH2OH
OH
OH
OH
fructose-6-phosphate
ATP
ADP
O
CH2OP CH2OP
OH
OH
OHfructose-1,6-bisphosphate
phosphofructokinase
aldolase
CH2OH
C
CH2OP
Odihydroxy acetone phosphate
CC
CH2OP
OHH
HO
glyceraldehyde-3-phosphate
NAD+NADHPi
CC
CH2OP
OHH
OPO
1,3-diphosphoglycerate
glyceraldehyde - phosphate dehydrogenase
ADPATP
CC
CH2OP
OHH
OO
phosphoglycerate kinase
3-phosphoglycerate
CC
CH2OH
OPH
OO
phosphoglycerate mutase
2-phosphoglycerate
OH2
phosphoenolpyruvateenolase
CC
CH2
OP
OO ADP ATP
C
C
CH3
O
OO
pyruvate kinase
pyruvate
triose phosphate isomerase
Hexokinase reaction
O
OHOH
OH
OH
CH2OH
glucose
ATP ADP
O
OHOH
OH
OH
CH2OP
Glucose-6-phosphate
hexokinase
• Irreversible• Kinase (phosphate transfer)• -16.7kJ
Hexose phosphate isomerase reaction
O
OHOH
OH
OH
CH2OP
Glucose-6-phosphate
hexose phosphate isomerase
O
CH2OPCH2OH
OH
OH
OH
fructose-6-phosphate
• Keto-aldol isomerization – Glucose to fructose
• 1.7 kJ
Phosphofructokinase reaction
O
CH2OPCH2OH
OH
OH
OH
ATPADP
O
CH2OP CH2OP
OH
OH
OHfructose-1,6-bisphosphatephosphofructokinase
• Same as hexokinase reaction• -14.2kJ• Major point of regulation
– Committed step– Stimulated by ADP and AMP– Inhibited by ATP and fatty acids
Aldolase Reaction
O
CH2OP CH2OP
OH
OH
OHfructose-1,6-bisphosphate
aldolase
CH2OH
C
CH2OP
O
dihydroxy acetone phosphate
CC
CH2OP
OHH
HO
glyceraldehyde-3-phosphate
+
• Reverse aldol condensation• 23.8kJ• Makes 2 3-Carbon molecules
Triose phosphate isomerase
CH2OH
C
CH2OP
O
dihydroxy acetone phosphate
CC
CH2OP
OHH
HO
glyceraldehyde-3-phosphate
triose phosphate isomerase
• Keto-enol isomerization (like hexose phosphate isomerase reaction)
• 7.5kJ• Net is 2 glyceraldehyde – 3 – phosphate• From now on each reaction times 2
Glyceraldehyde -3-phosphate dehydrogenase
CC
CH2OP
OHH
HO
glyceraldehyde-3-phosphate
NADH
CC
CH2OP
OHH
OPO
1,3-diphosphoglycerate
glyceraldehyde - phosphate dehydrogenase
NADPi
• Oxidation coupled to phosphorylation• Makes NADH• 6.3kJ• (remember X 2)
Phosphoglycerate Kinase
CC
CH2OP
OHH
OPO
1,3-diphosphoglycerate
ADP ATPCC
CH2OP
OHH
OO
phosphoglycerate kinase3-phosphoglycerate
• Phosphate transfer– Substrate level phosphorylation
• Driven by stabilization of carboxylate• -18.5kJ• Pulls previous reactions through
Phosphoglycerate mutase
CC
CH2OP
OHH
OO
3-phosphoglycerate
CC
CH2OH
OPH
OO
phosphoglycerate mutase
2-phosphoglycerate
• Moves from 3 - 2• 2 steps
– Makes 2,3– Removes 3
• 4.4kJ
enolase
CC
CH2OH
OPH
OO
2-phosphoglycerate
OH2
phosphoenolpyruvateenolase
CC
CH2
OP
OO
• Makes unstable enol intermediate• 7.5 kJ
Pyruvate kinase
phosphoenolpyruvate
CC
CH2
OP
OO ADP ATP
C
C
CH3
O
OO
pyruvate kinase
pyruvate
• Last reaction….woohoo• Substrate level phosphorylation• Stabilization of enol - keto• -31.4kJ
Net products from Glycolysis (per glucose)
• 2 pyruvate
• 2 NADH
• 2 ATP
• Total energy = -61.3 kJ– Sum of energies
Fates of pyruvate
CH3
O
O
O
CH3 OH CH3
OH
O
O
ethanolpyruvate
lactate
NAD+NAD+
NADH NADHCO2
CO2
HSCoA
CH3 SCoA
O
acetyl CoA
lactate dehydrogenase (LDH)pyruvate decarboxylase
pyruvate dehydrogenase
NADH
NAD+
Fates of Pyruvate
• Depend on organism and conditions• Yeast
– Anaerobic• Pyruvate decarboxylase• Makes alcohol
– Aerobic• Makes acetyl CoA --- energy or fat
• Others– Anaerobic
• LDH• Makes lactate• Sore muscles
– Aerobic• Acetyl Co A --- energy or fat
Glycogen
O
OOH
OH
OH
CH2OH
O
OH
OH
CH2OH
O
CH2
O
OOH
OHO
CH2OH
O
OHOH
OH
CH2OH
O
OH
OH
O
O
OH
OH
OH
CH2OH
Glycogenolysis
Glycogen breakdown
• Glycogen phosphorylase breaks down alpha 1,4 linkages– Makes glucose-1-phosphate– Enzyme changes to glucose-6-phosphate and enters
glycolysis there
• Can’t break 1,6 linkages– Debranching enzyme breaks 1,6 (when 4 sugars
away from branch) and adds to end– Glycogen phosphorylase takes over and breaks down
the rest
Other sugars
• Fructose– Comes in at fructose-6-p and immediately
phosphorylated• Lipogenic…after branch to glycogen…makes
acetyl CoA
• Lactose– Glucose and galactose
• Galactose– Epimerase turns into glucose-6-P and enters there
gluconeogenesis
• Making glucose from pyruvate– In liver– Uses same enzymes as glycolysis except
where nonequilibrium reactions– Uses NADPH instead of NADH
