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metabolic pathways
respiration
chapter 13-14
• metabolism
• metabolic pathways
• usually in specific location
• convert substrates to end products via intermediates
• anabolic
• catabolic
redox reactions
mitochondria
• oxidation-reduction reactions
• reducing agent - electron donor
• oxidizing agent - electron acceptor
• shape
• highly variable
• can fuse or split
• structure
• outer membrane
• inner membrane
• cristae
• intermembrane space
• mitochondrial matrix
• free ribosomes
• respiratory enzymes
mitochondria
cellular respiration
• reproduction
• can fuse or split
• DRP1 • interacts with ER tubules
• oligomerizes at constriction point
• combustion
H + 1/ O
2
2
+
2H
2
1/
2
O
1/
2
O
2
(from food via NADH)
Controlled
release of
energy for
synthesis of
ATP
2 H+ + 2 e−
Free energy, G
rt
spo
tran
tron ain
ch
DRP1
Explosive
release of
heat and light
energy
ATP
Elec
Free energy, G
becomes oxidized
ATP
becomes reduced
ATP
2 e−
ER tubule
2 H+
HO
HO
2
2
(a) Uncontrolled reaction
(b) Cellular respiration
oxidizing agents
cellular respiration
• NADH - (nicotinamide adenine dinucleotide)
• glycolysis
• pyruvate oxidation - citric acid cycle
• oxidative phosphorylation
NAD+
2
NADH
Dehydrogenase
Electrons
carried
via NADH
Reduction of NAD+
(from food)
Nicotinamide
(oxidized form)
Oxidation of NADH
Nicotinamide
(reduced form)
Glycolysis
Glucose
Pyruvate
Electrons carried
via NADH and
FADH
2
Pyruvate
oxidation
Acetyl CoA
Citric
acid
cycle
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
MITOCHONDRION
CYTOSOL
ATP
Substrate-level
phosphorylation
ATP
Substrate-level
phosphorylation
ATP
Oxidative phosphorylation
glycolysis
glycolysis
• glycolysis -
• glycolysis -
Glycolysis: Energy Investment Phase
splitting of sugar
• energy
investment
• energy payoff
ATP
Glucose Glucose 6-phosphate
ADP
Hexokinase
1
ATP
Fructose 1,6-bisphosphate
ADP
Fructose 6-phosphate
Phosphogluco-
isomerase
Phospho-
fructokinase
2
Aldolase
3
Dihydroxyacetone
phosphate
4
Glyceraldehyde
3-phosphate
Isomerase
5
To
step 6
splitting of
sugar
• energy
investment
• energy payoff
Glycolysis: Energy Investment Phase
ATP
Glucose Glucose 6-phosphate
ADP
ATP
Fructose 1,6-bisphosphate
ADP
Fructose 6-phosphate
Phosphogluco-
isomerase
Hexokinase
1
Phospho-
fructokinase
2
Aldolase
3
Dihydroxyacetone
phosphate
4
Glyceraldehyde
3-phosphate
Isomerase
To
step 6
5
Glycolysis: Energy Payoff Phase
2 ATP
2 NADH
2 NAD+
+ 2 H+
Triose
phosphate
dehydrogenase2
6
P
2
2
Phospho-
glycerokinase
i
2 ATP
2H O
2 ADP
2
2 ADP
1,3-Bisphospho-
glycerate
7
2
Phospho-
glyceromutase
3-Phospho-
glycerate
8
Enolase
9
2-Phospho-
glycerate
Pyruvate
kinase
Phosphoenol-
10
pyruvate (PEP)
oxidation of pyruvate
sources of Acetyl CoA
• preparation of pyruvate for citric acid cycle
• pyruvate dehydrogenase complex
• 3 reactions
MITOCHONDRION
• Acetyl CoA • used to fuel the citric acid cycle
• catabolic sources
• pyruvate - from glucose
• fatty acid cycle (spiral)
• digestion of amino acids
CYTOSOL
CO Coenzyme A
2
3
1
Proteins
Amino
acids
Carbohydrates
Sugars
Glycolysis
Glucose
Glyceraldehyde 3- P
2
Pyruvate
NAD+
NADH
NH
3
+
H+
Acetyl CoA
Pyruvate
Acetyl CoA
Transport protein
Citric
acid
cycle
Oxidative
phosphorylation
Pyruvate
Fats
Glycerol
Fatty
acids
fatty acid spiral
citric acid cycle
• fatty acid activated
• Fatty acyl-CoA synthetase
• 2 carbons trimmed per turn
• steps
• activation
• oxidation
• hydration
• oxidation
• thiolysis
thiolysis
• other names
• TCA cycle, Krebs cycle
Pyruvate
CO
NAD+
2
CoA
NADH
+ H+
Acetyl CoA
CoA
CoA
Citric
acid
cycle
oxidation
2 CO
FADH
2
hydration
2
3 NAD+
3 NADH
FAD
+ 3 H+
ADP + P
oxidation
citric acid cycle
electron transport
• stepwise cycle
• oxaloacetate + acetyl CoA
• Reduced coenzymes
• NADH and FADH2
• used to produce ATP• account for most of the energy produced
oxidative
phosphorylation
•
• energy from redox reactions used to produce ATP
--> (6 carbon)
• citrate decomposed back
to oxaloacetate
i
ATP
Acetyl CoA
CoA-SH
NADH
HO
1
+ H+
2
NAD+
Oxaloacetate
8
2
Malate
Citrate
Isocitrate
NAD+
Citric
acid
cycle
7
HO
2
NADH
3
H+
+ H+
H+
CO
2
H+
Fumarate
CoA-SH
α-Ketoglutarate
6
4
CoA-SH
5
FADH
2
NAD+
FAD
i
GTP
GDP
Succinyl
CoA
IV
Q
2
III
I
+ H+
II
FADH
ADP
ATP
H+
Cyt c
CO
NADH
P
Succinate
Protein
complex
of electron
carriers
FAD
2 H+ + 1/ O
2
ATP
synth-
ase
HO
2
2
2
NADH
NAD+
ADP + P
(carrying electrons
from food)
ATP
i
H+
1
Electron transport chain
Oxidative phosphorylation
2
Chemiosmosis
NAD+
FADH
2
2 e−
40
I
FMN
Fe•S
Fe•S
Multiprotein
complexes
FAD
II
Q
III
Cyt b
Fe•S
30
Cyt c
IV
1
Cyt c
Cyt a
Cyt a
3
20
2 e−
10
(originally from NADH or FADH )
• types of electron carriers
• flavoproteins
• cytochromes
• three copper atoms
• ubiquinone
• iron sulfur proteins
NADH
50
2 e−
NAD+
FADH
2
2 e−
40
FMN
Fe•S
II
Fe•S
Q
III
Cyt b
Fe•S
30
Cyt c
2 H+ + 1/ O
2
IV
1
Cyt c
Cyt a
Cyt a
3
20
2 e−
10
(originally from NADH or FADH )
2
0
Multiprotein
complexes
FAD
I
2
2
e−
2
electrons
• each time, electrons lose
free energy
• H+ pumped out
• chemiosmosis
• potential energy stored in
H+ gradient used to
synthesize ATP
NADH
50
Free energy (G) relative to O (kcal/mol)
• electron tranport chain
• multiprotein complexes
• accept and donate
electron transport
Free energy (G) relative to O (kcal/mol)
electron transport
2
2 H+ + 1/ O
0
2
2
HO
HO
2
electron transport
INTERMEMBRANE SPACE
NADH
2
e−
NAD+
FADH
2
2 e−
40
I
FMN
Fe•S
Fe•S
2
Multiprotein
complexes
FAD
II
Q
III
Cyt b
30
Fe•S
Cyt c
IV
1
Cyt c
Cyt a
20
10
2
proton motive force
50
Free energy (G) relative to O (kcal/mol)
• complex I
• NADH dehydrogenase
• flavin mononucleotide
• iron-sulfur protein
complex
II
•
• succinate dehydrogenase
• FADH2 - lower energy
• complex III
• cytochrome bc1
• complex IV
• cytocrome c oxidase
Cyt a
• ATP-synthase
• exergonic flow of H+ used to power ATP production
• F0
• 10-14 subunits
• rotor turns
F0
F
• 1
• catalytic portion
H+
Stator
Rotor
3
Internal
rod
F1
2 e−
(originally from NADH or FADH )
Catalytic
knob
2
ADP
0
2
2 H+ + 1/ O
2
+
2
P
i
MITOCHONDRIAL MATRIX
HO
2
ATP
proton motive force
binding change mech.
INTERMEMBRANE SPACE
• molecular mill
• F0
• H+ flows into half channel
• binds with rotor subunits
• rotor turns
• F1
• internal rod spins
• catalytic portion fixed
H+
Stator
Rotor
• catalysis of ATP
• three binding sites
• three conformations (active site)
• loose
•
binds with ADP and P
• tight
•
•
Internal
rod
•
Catalytic
knob
ATP formed
open
ATP released
ADP
+
P
ATP
i
MITOCHONDRIAL MATRIX
energy accounting
anaerobic
• about 32 ATP molecules produced from glucose
• fermentation
• glycolysis
• pyruvate
• pyruvate
• reduced to lactate
• no release of CO2
Electron shuttles
span membrane
MITOCHONDRION
2 NADH
or
2 FADH
2
2 NADH
Glycolysis
Glucose
2 Pyruvate
2 NADH
Pyruvate oxidation
2 Acetyl CoA
+ 2 ATP
Citric
acid
cycle
+ 2 ATP
Maximum per glucose:
CYTOSOL
6 NADH
About
30 or 32 ATP
2 FADH
2
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
+ about 26 or 28 ATP
2 ADP + 2 P
Glucose
2 ATP
i
Glycolysis
2 NAD
+
2 NADH
+2 H +
Lactate dehydrogenase
2 Lactate
2 Pyruvate
anaerobic
related organelles
• eukaryotes
• if O2 not available • pyruvate undergoes fermentation
• peroxisomes
• similar to mitochondria in some ways
• form from pre-existing organelles
• import pre-formed proteins
• oxidative metabolism
related organelles
• glyoxysomes
• specialized peroxisome in plants
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