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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
CHAPTER 7LECTURE
SLIDES
Prepared by
Brenda LeadyUniversity of Toledo
2
Cellular respiration
Process by which living cells obtain energy from organic molecules and release waste products
Primary aim to make ATP and NADH Nutrients are broken down and re-arranged into
high energy molecules.
Metabolism: all the chemical processes of the body (cell)
When we breath we take in the oxygen needed for cellular respiration)
Cellular respiration
Anaerobic respiration Without oxygen consumption.
Aerobic respiration uses oxygenO2 consumed and CO2 released
Focus on glucose but other organic molecules also used.
4
Glucose metabolism
C6H12O6 + 6O2 → 6CO2 + 6H2O
ATP, NADH, FADH2
4 metabolic pathways
1. Glycolysis
2. Breakdown of pyruvate to an acetyl group
3. Citric acid cycle
4. Oxidative phosphorylation
5
1
2 pyruvate
2 pyruvate
C C C C C C
C C C2
2
2 acetyl
C C C2
C C2
2 pyruvate
2 CO2
2 CO2
2 CO2
3
4 CO2
C C2
2 acetyl
Cytosol
2 NADH
2 NADH
+2 ATP
Via chemiosmosis
6 NADH 2 FADH2
Glycolysis:Glucose
Outer mitochondrialmembrane
Breakdown ofpyruvate:
2CO2 + 2acetyl
Citric acidcycle:
Via substrate-levelphosphorylation
Via substrate-levelphosphorylation
Mitochondrialmatrix
Inner mitochondrial membrane
+2 ATP +30–34 ATP
4 Oxidativephosphorylation:The oxidation of NADHand FADH2 via theelectron transportchain provides energyto make more ATPvia the ATP synthase.O2 is consumed.
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6
Stage 1: Glycolysis
Glycolysis can occur with or without oxygen.
Steps in glycolysis nearly identical in all living species
10 steps in 3 phases1. Energy investment (2 ATP)2. Cleavage3. Energy liberation
7
3 phases of glycolysis1. Energy investment
Steps 1-3 2 ATP hydrolyzed to create fructose-1,6 bisphosphate
2. Cleavage Steps 4-5 6 carbon molecule broken into two 3 carbon molecules of
glyceraldehyde-3-phosphate3. Energy liberation
Steps 6-10 Two glyceraldehyde-3-phosphate molecules broken down into
two pyruvate molecules producing 2 NADH and 4 ATP Net yield in ATP of 2
Glycolysis occurs in the cytosol
9
C C C C C C
Glucose
OHH
HOHH
OH
O HH
HO
CH2OH
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10
ATP ATP
C C C C C C C C C C C C
Energy investment phase
Step 2 Step 3Step 1
GlucoseFructose-1,6-bisphosphate
OHH
HOHH
OH
O HH
HO
CH2OH
HHO
OH
OH
H
H
OCH2 PP O CH2O
Phase 1
2 ATP are hydrolyzed and the P- from the ATP is attached to the glucose
This phase raises the free energy level of the glucose which allows later Rxns to be exergonic.
11
C CCATP
C C C C C C C C C C C C
C CC
Cleavage phase
Energy investment phase Step 4 Step 5
Step 2 Step 3Step 1
Glucose Fructose-1,6-bisphosphate
OHH
HOHH
OH
O HH
HO
CH2OH
ATPH
HO
OH
OH
H
H
OCH2 PP O CH2O
P
CHOH
C
H
O
CH2O
P
CHOH
H
OC
CH2O
Two molecules ofglyceraldehyde-3-phosphate
The cleavage phase (steps 4-5) breaks the six carbon molecule into 2 three carbon molecules
(glyceraldehyde-3-phsphate)
12
C CC
Pi
ATP ATP
NADH ATP ATP
NADH ATP ATP
C C C C C C C C C C C C
C CC C CC
C CC
C O
C O
O–
CH3
C O
C O
O–
CH3
Cleavage phaseEnergy investment phase
Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Step 10
Energy liberation phaseSteps 6-10Liberates energy to produce energy intermediates
Step 2 Step 3Step 1
Glucose Fructose-1,6-bisphosphate
OHH
HOHH
OH
O HH
HO
CH2OH
HHO
OH
OH
H
H
OCH2 PP O CH2O
P
CHOH
C
H
O
CH2O
Pi
Two moleculesof pyruvate
P
CHOH
H
OC
CH2O
Two molecules ofglyceraldehyde-3-phosphate
Step 6, glyceraldehyde-3-phosphate is oxidized to yield NADH. (x2)Steps 7 and 10, 4 ATP are made by substrate level phosphorolation.
Glycolysis Net yield is 2 ATP and 2 NADH and
2 pyruvate molecules.
13
ATP
OHH
HOHH
OH
O HH
HO
Glucose
CH2OH
Glycolysis
14
ATP ADP
OHH
HOHH
OH
O HH
HO
OCH2P
Hexokinase
OHH
HOHH
OH
O HH
HO
Glucose
CH2OH
Glucose-6-phosphate
1. Glucose is phosphorylated by ATP.
15
ATP ADPATP
Hexokinase
GlucoseOHH
HOHH
OH
O HH
HO
CH2OH
Glucose-6-phosphate
Phosphogluco–isomerase
Fructose-6-phosphateOHH
HOHH
OH
O HH
HO
OCH2P
HO
OH
OH
H
HH
OCH2P
CH2OHO
2. Glucose-6-phosphate is rearranged into fructose-6-phosphate
16
ATP ADPATP ADP
Hexokinase Aldolase
- -OHH
HOHH
OH
O HH
HO
Glucose
CH2OH
Glucose-6-phosphate
Phosphogluco–isomerase
Fructose-6-phosphate
Phosphofructo–kinase
Fructose-1,6-bisphosphateOHH
HOHH
OH
O HH
HO
OCH2P
OH H
HOOH
HH
OCH2P
CH2OHO
HO
OH
OH
H
HH
OCH2P PCH2OO
3. Fructose-6-phosphate is phosphorylated to make fructose-1,6-bisphosphate (ATP is used)
17
ATP ADPATP ADP
OHH
HOHH
OH
O HH
HO
OCH2P
Hexokinase Aldolase
- -
Isomerase
OHH
HOHH
OH
O HH
HO
Glucose
CH2OH
Glucose-6-phosphate
Phosphogluco–isomerase
Fructose-6-phosphate
Phosphofructo–kinase
Fructose-1,6-bisphosphate
P
CHOH
H
C O
CH2O
Glyceraldehyde-3-phosphate (X2)
Dihydroxyacetonephosphate
C O
OCH2P
CH2OH
HO
OH
OH
H
HH
OCH2P
CH2OHO
HO
OH
OH
H
HH
OCH2P PCH2OO
4. Fructose-1,6-bisphosphate is cleaved into Dihydroxyacetone and
Glyceraldehyde-3-phosphate
Dihydroxyacetone is isomerized into another glyceraldehyde-3-phosphate the result is 2 glyceraldehyde-3-phosphate
18
Isomerase
P
CHOH
H
C O
CH2O
Glyceraldehyde-3-phosphate
Dihydroxyacetonephosphate
C O
OCH2P
CH2OH
5. The Dihydroxyacetone phosphateis Isomerized into Glyceraldehyde-3-phosphate.
(X2)
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2 NADH
2 NADH
6 NADH
GlucoseGlycolysis:
2
2
+2 ATP
2 pyruvate 2
2 FADH2
Break-down ofpyruvate
+2 ATP
Citric acidcycle
+30–34 ATP
Oxidativephosphorylation
ATP ADPATP ADP
OHH
HOHH
OH
O HH
HO
OCH2P
CO2
CO2
Hexokinase Aldolase
- -
Isomerase
OHH
HOHH
OH
O HH
HO
Glucose
CH2OH
Glucose-6-phosphate
Phosphogluco–isomerase
Fructose-6-phosphate
Phosphofructo–kinase
Fructose-1,6-bisphosphate
P
CHOH
H
C O
CH2O
Glyceraldehyde-3-phosphate (× 2)
Dihydroxyacetonephosphate
C O
OCH2P
CH2OH
CO2
HO
OH
OH
H
HH
OCH2P
CH2OHO
HO
OH
OH
H
HH
OCH2P PCH2OO
19
20
Isomerase
P
CHOH
H
C O
CH2O
Glyceraldehyde-3-phosphate (× 2)
Dihydroxyacetonephosphate
C O
OCH2P
CH2OH
2 Pi
2 NAD+ +2 H+
2 NADH
Unstable phosphate bond
Glyceraldehyde-3-phosphatedehydrogenase
~
P
CHOH
OOCP
CH2O
1, 3 -bisphosphoglycerate( × 2 )
6. Glyceraldehyde-3-phosphate is oxidized to 1,3-
bisphosphoglycerate with the production of NADH
The phosphate group is destabilized making it ready for exergonic reaction
21
2 ATP
Isomerase
P
CHOH
H
C O
CH2O
Glyceraldehyde-3-phosphate (× 2)
Dihydroxyacetonephosphate
C O
OCH2P
CH2OH
2 ADP
2 Pi
2 NAD+ +2 H+
2 NADH
Unstable phosphate bond
Glyceraldehyde-3-phosphatedehydrogenase
~
P
CHOH
OOCP
CH2O
1, 3 -bisphosphoglycerate( × 2 )
Phosphoglycero–kinase
P
CHOH
OC
O
CH2O
3-phosphoglycerate( × 2 )
7. A phosphate is removed from 1,3-bisphosphoglycerate to produce 3-phosphoglycerate.
The phosphate is transferred to ADP to make ATP. (x2, yield 2 ATP)
22
2 ATP
Isomerase
P
CHOH
H
C O
CH2O
Glyceraldehyde-3-phosphate (× 2)
Dihydroxyacetonephosphate
C O
OCH2P
CH2OH
2 ADP
2 Pi
2 NAD+ +2 H+
PHCO
OC
O–
CH 2OH
2 NADH
Phosphoglycero–mutase
Unstable phosphate bond
Glyceraldehyde-3-phosphatedehydrogenase
~
P
CHOH
OOCP
CH2O
1, 3 -bisphosphoglycerate( × 2 )
Phosphoglycero–kinase
P
CHOH
OC
O
CH2O
3-phosphoglycerate( × 2 )
2-phosphoglycerate( × 2 )
8. The phosphate group is moved in 3-phosphoglycerate to form 2-phosphoglycerate
23
2 ATP
Isomerase
P
CHOH
H
C O
CH2O
Glyceraldehyde-3-phosphate (× 2)
Dihydroxyacetonephosphate
C O
OCH2P
CH2OH
2 ADP
2 Pi
2 NAD+ +2 H+
PHCO
OC
O–
CH 2OH
~PCO
OC
O–
CH2
2 NADH
Phosphoglycero–mutase
Enolase
Unstable phosphate bondUnstable phosphate bond
Glyceraldehyde-3-phosphatedehydrogenase
~
P
CHOH
OOCP
CH2O
1, 3 -bisphosphoglycerate( × 2 )
Phosphoglycero–kinase
P
CHOH
OC
O
CH2O
3-phosphoglycerate( × 2 )
2-phosphoglycerate( × 2 )
2 H2O
Phosphoenolpyruvate( × 2 )
9. A water molecule is removed from 2-phosphoglycerate to form Phosphoenolpyruvate.
The phosphate group is destabilized in the process.
24
2 ATP2 ATP
Isomerase
P
CHOH
H
C O
CH2O
Glyceraldehyde-3-phosphate (× 2)
Dihydroxyacetonephosphate
C O
OCH2P
CH2OH
2 ADP 2 ADP
2 Pi
2 NAD+ +2 H+
PHCO
OC
O–
CH 2OH
~PCO
OC
O–
CH2
OC
O–
CH3
OC
2 NADH
Phosphoglycero–mutase
Enolase Pyruvate kinase
Unstable phosphate bondUnstable phosphate bond
Glyceraldehyde-3-phosphatedehydrogenase
~
P
CHOH
OOCP
CH2O
1, 3 -bisphosphoglycerate( × 2 )
Phosphoglycero–kinase
P
CHOH
OC
O
CH2O
3-phosphoglycerate( × 2 )
2-phosphoglycerate( × 2 )
2 H2O
Phosphoenolpyruvate( × 2 )
Pyruvate( × 2 )
10. A phosphate is removed from Phosphoenolpyruvate to form Pyruvate.
The phosphate is transferred to ADP.
The end products of glycolysis is 2 pyruvate, 2 H+, 2 NADH, 2 ATP and 2 H2O
2 H2O
Control of glycolyis Feedback inhibition occurs when ATP
concentrations in the cell are high.
ATP binds to the allosteric site in fructokinase preventing the action of this enzyme (step 3).
This prevents the further breakdown of glucose inhibiting the overproduction of ATP.
26
Stage 2: Breakdown of pyruvate to an acetyl group In eukaryotes, pyruvate is transported to the
mitochondrial matrix Broken down by pyruvate dehydrogenase Molecule of CO2 removed from each pyruvate Remaining acetyl group attached to CoA to
make acetyl CoA 1 NADH is made for each pyruvate
27
H+
OC
O–
CH3
OC
NADH+
NAD++ +CoA SH
CO2
Acetyl CoA
Outermembranechannel
H+/pyruvatesymporter
Pyruvatedehydrogenase
O
CoA
C
S
CH3
+
OC
O–
CH3
OC
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Pyruvate travels through a channel in the outer membrane and through an H+/pyruvate Symporter in the inner membrane to reach the matrix
28
H+
OC
O–
CH3
OC
NADH+
NAD++ +CoA SH
CO2
Acetyl CoA
Outermembranechannel
H+/pyruvatesymporter
Pyruvatedehydrogenase
O
CoA
C
S
CH3
+
OC
O–
CH3
OC
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Pyruvate is oxidized to an acetyl group (CO2 and NADH is made).The acetyl group is transferred to a coenzyme-A Acetyl CoA
29
Stage 3: Citric acid cycle(Acetyl CoA)
Metabolic cycleParticular molecules enter while others leave,
involving a series of organic molecules regenerated with each cycle
Acetyl is removed from Acetyl CoA and attached to oxaloacetate to form citrate or citric acid
Series of steps releases 2CO2, 1ATP, 3NADH, and 1 FADH2
Oxaloacetate is regenerated to start the cycle again
30
Citric acid cycle
GTP
ATP
5
NADH
CO2
CO2
3
4
CCCCC
1
2
CCCC
NADH
8
CCCC7
CCCC
FADH2
6
CCCC
+2 ATP
2 CO2
2 NADH
2 NADH
6 NADH 2 FADH2
2 CO2
2 CO2
+2 ATP
2 pyruvate
CCCC
+30–34 ATP
CCCCCCCCCCCC
NADH
Acetyl CoA
Oxaloacetate
Citrate
Glycolysis:Glucose
Break-down ofpyruvate
Oxidativephosphorylation
O
C S CoAH2C
Citricacidcycle
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The citric acid cycle is “cyclic” because it involves a series of organic moleculesthat are regenerated after the turn of the cycle.
31
Acetyl CoA
CoA—SH
C C
C C C C C C
COO–
CH2
C
CH2
COO–
COO–HO
CoA
C
S
O
CH+
Citrate
1
H2O
Citratesynthetase
2A
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1. An acetyl group from acetyl CoA is attached to oxaloacetate to form citrate
32
Acetyl CoA
CoA—SH
C C
C C C C C C
C C C C C C
COO–
CH2
C
CH2
COO–
COO–HO
COO–
CH2
HC
CHHO
COO–
COO–
CoA
C
S
O
CH+
Citrate
Isocitrate
Aconitase
1
2B
H2O
Citratesynthetase
2A
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
2. Citrate is rearranged to an isomer called isocitrate
33
Acetyl CoA
CoA—SH
NAD+
NADH
C C
C C C C C C
C C C C C C C C C C C
CO2
COO–
CH2
C
CH2
COO–
COO–HO
COO–
CH2
HC
CHHO
COO–
COO–
COO–
CH2
CH2
C
COO–
O
+
CoA
C
S
O
CH+
Citrate
Isocitrate α-Ketoglutarate
Aconitase
1
2B
3
H2O
Citratesynthetase
2A
Isocitratedehydro-genase
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3. Isocitrate is oxidized to a-ketogluterate.(CO2 is released and NADH is formed)
34
Acetyl CoA
CoA—SH
NAD+
NAD+
NADH
NADH
CoA—SH
C C
C C C C C C
C C C C C C C C C C C CO2
CO2
C C C C
COO–
CH2
C
CH2
COO–
COO–HO
COO–
CH2
HC
CHHO
COO–
COO–
COO–
CH2
CH2
C
COO–
O
+
COO–
CH2
CH2
C
S
O
CoA
+
CoA
C
S
O
CH+
Citrate
Isocitrate α-Ketoglutarate
Succinyl-CoA
Aconitase
1
2B
34
H2O
Citratesynthetase
2A
Isocitratedehydro-genase
α-Ketoglutaratedehydrogenase
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
4. A-ketogluterate is oxidized as it combines with CoA to form succinyl CoA. (CO2 is released and NADH is formed)
35
C C C C
ATPAcetyl CoA
CoA—SH
GTP
ADP
GDP + Pi
CoA—SH
NAD+
NAD+
NADH
NADH
CoA—SH
C C
C C C C C C
C C C C C C C C C C C CO2
CO2
C C C C
COO–
CH2
C
CH2
COO–
COO–HO
COO–
CH2
HC
CHHO
COO–
COO–
COO–
CH2
CH2
C
COO–
O
+
COO–
CH2
CH2
C
S
O
CoA
+
CoA
C
S
O
CH+
Citrate
Isocitrate α-Ketoglutarate
Succinyl-CoA
Aconitase
1
2B
34
H2O
Citratesynthetase
Succinyl-CoAsynthetase
2A
Isocitratedehydro-genase
α-Ketoglutaratedehydrogenase
COO–
COO–
CH2
CH2
Succinate
5
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5. Succinyl CoA is broken down to CoA and succinate.This drives the formation of GTP from GDP and P.(GTP can donate a phosphate to ADP to form ATP)
36
ATPAcetyl CoA
CoA—SH
GTP
ADP
GDP + Pi
CoA—SH
NAD+
NAD+
NADH
NADH
CoA—SH
C C
C C C C C C
C C C C C C C C C C C CO2
CO2
C C C C
C C C C
COO–
CH2
C
CH2
COO–
COO–HO
COO–
CH2
HC
CHHO
COO–
COO–
COO–
CH2
CH2
C
COO–
O
+
COO–
CH2
CH2
C
S
O
CoA
+
COO–
COO–
CH
HC
CoA
C
S
O
CH+
Citrate
Isocitrate α-Ketoglutarate
Succinyl-CoA
Aconitase
Fumarase
Fumarate
1
2B
34
7
H2O
Citratesynthetase
Succinyl-CoAsynthetase
2A
Isocitratedehydro-genase
α-Ketoglutaratedehydrogenase
FADFADH2
C C C CCOO–
COO–
CH2
CH2
Succinate
Succinatedehydrogenase
6
5
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6. Succinate is oxidized to fumerate.(FADH2 is made)
37
C C C C
ATPAcetyl CoA
CoA—SH
GTP
ADP
GDP + Pi
CoA—SH
NAD+
NAD+
NADH
NADH
CoA—SH
C C
C C C C C C
C C C C C C C C C C C CO2
CO2
C C C C
C C C CC C C C
COO–
CH2
C
CH2
COO–
COO–HO
COO–
CH2
HC
CHHO
COO–
COO–
COO–
CH2
CH2
C
COO–
O
+
COO–
CH2
CH2
C
S
O
CoA
+
COO–
COO–
CH
HC
COO–
COO–
CHHO
CH2
CoA
C
S
O
CH+
Citrate
Isocitrate α-Ketoglutarate
Succinyl-CoA
Aconitase
Fumarase
FumarateMalate
1
2B
34
78
H2O
Citratesynthetase
Succinyl-CoAsynthetase
H2O
2A
Isocitratedehydro-genase
α-Ketoglutaratedehydrogenase
FADFADH2
COO–
COO–
CH2
CH2
Succinate
Succinatedehydrogenase
6
5
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7. Fumerate combines with water to form malate.
38
ATPAcetyl CoA
CoA—SH
GTP
ADP
GDP + Pi
CoA—SH
Citric acid cycle
NAD+
NADH
NAD+
NAD+
NADH
NADH
CoA—SH
C C
C C C C C C
C C C C C C C C C C C CO2
CO2
C C C C
C C C CC C C C
C C C C
COO–
CH2
C
CH2
COO–
COO–HO
COO–
CH2
HC
CHHO
COO–
COO–
COO–
CH2
CH2
C
COO–
O
+
COO–
CH2
CH2
C
S
O
CoA
+
COO–
COO–
CH
HC
COO–
COO–
CHHO
CH2
COO–
COO–
CO
CH2
CoA
C
S
O
CH+
Citrate
Isocitrate α-Ketoglutarate
Succinyl-CoA
Aconitase
Fumarase
FumarateMalate
Oxaloacetate
1
2B
34
78
H2O
Citratesynthetase
Succinyl-CoAsynthetase
H2O
2A
Isocitratedehydro-genase
α-Ketoglutaratedehydrogenase
Malatedehydro-genase
FADFADH2
C C C CCOO–
COO–
CH2
CH2
Succinate
Succinatedehydrogenase
6
5
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Malate is oxidized to Oxaloacetate.(the cycle can begin again)
Control of the citric acid cycle Competitive inhibition
Oxaloacitate is a competitive inhibitor of succinate dehydrogenase (catalizes step 6)
When the oxaloacitate level becomes too high, succinate dehydrogenase is inhibited and the citric acid cycle slows down.
On to the oxidative phosphorylation
Up to this point we have yielded 6 molecules of CO2, 4 molecules of ATP, 10 molecules of NADH and 2 molecules of FADH2
41
Stage 4: Oxidative phosphorylation
High energy electrons are removed from NADH and FADH2 to make ATP
Typically requires oxygen Oxidative process involves electron
transport chain Phosphorylation occurs by ATP synthase
42
Oxidation: ETC
Electron transport chains (ETC) Is a Group of protein and small organic molecules
embedded in the inner mitochondrial membrane
These proteins and molecules can accept and donate electrons in a linear manner in a series of redox reactions.
Electrons are transferred to components with increasing electronegativity.
The end of the line is Oxygen which is the most electronegative. (final electron acceptor)
Movement of these electrons generates a H+ (proton) electrochemical gradient/ proton-motive force The transfer of the electrons is highly exergonic
and free energy can be harnessed to pump H+ across the inner mitochondrial membrane creating a proton electrochemical gradient.
The hydrogens (protons) flow through an enzyme (ATP Synthase) down its concentration gradient.
ATP Synthase harnesses free energy from the flow of protons to attach phosphates to ADP generating ATP.
Kinetic energy of the H+ gradient is converted to chemical bond energy of ATP
This process is called chemiosmosis.
45
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NAD+
c
I
III
II
IV
H2O
Q
Matrix
+
NADH dehydrogenase
Ubiquinone
Cytochrome b-c1
Cytochrome c
Cytochrome oxidase
ATP synthase
Succinatereductase
Inner mitochondrialmembrane
ATPsynthesis
Electrontransportchain
Intermembranespace
movement
e– movement
KEYH+
NADH
FAD + 2
H+
H+H+
H+
H+
H+
H+
H+
H+
H+
H+H+
H+
H+
H+
H+
H+
H- -
FADH2
ADP + Pi
H+
2 H+ + ½ O2
ATP
MatrixIntermembranespaceMembrane proteins
and components accept and Transfer e- in a highly Exergonic Rxn. Which is used to drive H+ against its Concentration gradient.
The flow of H+ through theATP synthase enzyme provides free energy for the phosphorolation of ADP to ATP.
Phosphorylation by ATP synthase
Lipid bilayer of inner mitochondrial membrane relatively impermeable to H+
H+ can only pass through ATP synthase Harnesses the free energy release to
synthesize ATP from ADP Chemiosmosis - chemical synthesis of ATP
as a result of pushing H + across a membrane
46
47
NADH oxidation and ATP synthesis Oxidation of NADH and FADH results in
electrochemical gradient used to synthesize ATP (FADH donates H+ to the succinate reductase enzyme)
30-34 ATP molecules per glucose molecule broken down into CO2 and H2O
Rarely achieve maximal amountNADH used in anabolic pathwaysH+ gradient used for other purposes
48
ATP synthase
Enzyme Energy conversion- H+ electrochemical
gradient or proton motive force converted to chemical bond energy in ATP
Racker and Stoeckenius confirmed ATP uses an H+ electrochemical gradient
YIELDS
Glycolyis: 2 ATP
Citric Acid Cycle: 2 ATP
Oxidative Phosphorylation: 30-34 ATP
ATP synthase
A Rotary machine that makes ATP as it spins
51
ATP synthase
Vesicle
Bacteriorhodopsin(light-driven H+ pump)
ADPPi
No H+ gradient
Light rays
H+ gradient
ATP
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52
H+
a
b
cc
c
H+
Matrix
Intermembranespace
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
ATPADP + PiH+ passes through the c unitCausing the Y unit to rotateClockwise. Each 120 deg. turnCauses a conformational changeThat attaches P to ADP.
Conf. 1: ADP and P bindConf. 2: ADP and P are bondedConf 3: ATP is released
Chemicals can inhibit e- flow along ETC
Cyanide: inhibits cytochrome oxidase
This shuts down the ETC preventing cells from making enough ATP for survival
Yoshida and Kinosita deomonstrate that the γ subunit of the ATP synthase spins
Masasuke Yoshida, Kazuhiko Kinosita, and colleagues set out to experimentally visualize the rotary nature of the ATP synthase
Released membrane embedded portion and adhered it to a slide
Visualize γ subunit using fluorescence Added ATP to make reaction run backward Rotated counterclockwise to hydrolyze ATP
Rotate clockwise to synthesize ATP
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Experimental level Conceptual level
No ATP added
ATP Rotation
ATP added
No rotation observed.
Rotation was observed as shown below. This is a time-lapse view of the rotation in action.
Control:
Linker proteins
33 complex
Slide
+ ATP: counterclockwiserotation
Fluorescencemicroscope
Fluorescentactinfilament
ATPATP
Add linker proteinsand fluorescentactin filaments.
Add purifiedcomplex.
Cancer cells usually favor glycolysis Many disease associated with alterations in
carbohydrate metabolism Warburg effect- cancer cells preferentially use
glycolysis while decreasing oxidative phosphorylation Used to diagnose cancers in PET scans Glycolytic enzymes overexpressed in 80% of all types
of cancers Caused by genetic and environmental factors-
mutations and low oxygen
58
Other organic molecules
Focus on glucose but other carbohydrates, proteins and fats also used for energy
Enter into glycolysis or citric acid cycle at different points
Utilizing the same pathways for breakdown increases efficiency
Metabolism can also be used to make other molecules (anabolism)
Amino Acids and Fats
Can enter the later stages of glycolysis, the citric acid cycle or at different points along the pathway after being modified.
Amino Acids and Fats
Some breakdown products of proteins enter into the later stages of glycolysis or enter the citric acid cycle.
Ex. Acetyl groups from some amino acids can be removed and attached to CoA to become Acetyl CoA which enters the citric acid cycle.
Amino Acids and Fats
Fats can be broken down to glycerol and 2 fatty acids (acyls).
Glycerol can be modified into glyceraldehyde-3-phosphate and enter glycolysis at step 5.
The 2 fatty acetyl tails can be removed and combined with CoA Acetyl-CoA then enter the citric acid cycle
Amino Acids and Fats
After modification proteins and fats use the same enzymes and pathways.
By using the same pathways and enzymes cellular metabolism is more efficient
63
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Proteins Carbohydrates Fats
Sugars
Pyruvate
Acetyl CoA
Aminoacids
Glycolysis:Glucose
Glyceraldehyde-3-phosphate
Citricacidcycle
Oxidativephosphorylation
Glycerol Fattyacids
© The McGraw-Hill Companies, Inc./Ernie Friedlander/Cole Group/Getty Images
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7.3 Anaerobic metabolism
For environments that lack oxygen or during oxygen deficits
2 strategies
1. Use substance other than O2 as final electron acceptor in electron transport chain
2. Produce ATP only via substrate-level phosphorylation
Other acceptors
E. coli uses nitrate (NO3
-) under anaerobic conditions
Makes ATP via chemiosmosis even under anaerobic conditions
Nitrate is the final acceptor instead of O2
65
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NADH
NAD+ +
Ubiquinone
Cytochrome b
Nitrate reductase
ATP
ATP synthase
Cytoplasm
NADH dehydrogenase
H+
Extracellularfluid
+ PiADP
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
NO2– + H2O
NO3– + 2 H+
H+ movement
KE Y
e– movement
Fermentation : Breakdown of organic molecules to produce energy without oxygen.
Many organisms can only use O2 as final electron acceptor
Make ATP via glycolysis only:
The problem: Glycolysis needs NAD (to continue) and generates NADH NADH produces free radicals in high concentrations We need to reduce the NADH to NAD
66
The solution
Muscle cells produce lactate (lactic acid) The pyruvate is converted to lactate.
The electrons to reduce pyruvate to lactate are derived from oxidation of NADH which produces NAD.
Once oxygen is restored the lactate is converted back to pyruvate for energy or may be converted to glucose by the liver.
Yeast cells make ethanol
The pyruvate is broken down to CO2 and acetaldhyde.
The acetaldehyde is reduced to ethanol by oxidation of NADH to NAD
Fermentation produces far less ATP (2 ATP per
glucose molecule) than oxidative phosphorylation (34-38 ATP).
69
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(a) Production of lactic acid (b) Production of ethanol
2 lactate (secreted from the cell)
2 H1
2 NAD+ + 2 H+ 2 NADH
2 ATP
2 ethanol (secreted from the cell) 2 acetaldehyde
2 H+
2 pyruvate
2 NAD+ + 2 H+ 2 NADH
GlycolysisGlucose
2 pyruvate
2 ATP
GlycolysisGlucose
O
OC
O—
C
CH3
O
H OHC
C
O—
CH3
+ 2 Pi2 ADP
O
OC
O—
C
CH3
2 CO2
H OHC
H
CH3
OC
H
CH3
(weights): © Bill Aron/Photo Edit; (wine barrels): © Jeff Greenberg/The Image Works
+ 2 Pi2 ADP
END HERE
SKIP SECTION 7.3
71
Secondary Metabolism
Primary metabolism- essential for cell structure and function
Secondary metabolism- synthesis of secondary metabolites that are not necessary for cell structure and growth
Secondary metabolites unique to a species or group
Roles in defense, attraction, protection, competition
72
4 categories
Phenolics Antioxidants with intense flavors and smells
Alkaloids Bitter-tasting molecules for defense
Terpenoids Intense smells and colors
Polyketides Chemical weapons
73
74
75
76
1. Identify the 4 steps of glucose metabolism. 2. What is the purpose for changing
glucose into fructose1,6 bisphosphate? 3. Where do the Phosphates come from
for the above reaction?
4. The citric acid cycle is controlled by
____________. 5. The equation, C6H12O6+ 6O2 6CO2+ 6H2O (ATP + Heat), describes which
of the following processes? A. photosynthesis B. cell respiration C. cell fermentation D. glycolysis E. anaerobic metabolism
6.What is produced from pyruvate in muscle cells under anaerobic conditions?
Which of the following processes will occur in the presence or absence of oxygen? A. glycolysis B. electron transport chain C. oxidative phosphorylation D. cellular respiration E. citric acid cycle