Krebs cycle
Jan 12, 2016
Krebs cycle
Krebs Cycle (Citric acid cycle)
Series of 8 sequential reactions
Matrix of the mitorchondria
Synthesis of 2 ATP Generation of 8
energetic electrons
4 CO2 molecules
Krebs Cycle
Reaction 1: Condensation 2-carbon acetyl group from acetyl-
CoA Joins with oxaloacetate a four-
carbon molecule Forms a six-carbon molecule,
citrate.
Reaction 2: Isomerization Hydroxyl (-OH) group of citrate is
repositioned A water molecule is removed from one
carbon Water is added to another carbon on
the same citrate molecule. As a result, an –H group & an –OH group
change positions. Product is isocitrate-an isomer of
citrate
Reaction 3: The First Oxidation First energy yielding step of cycle Isocitrate undergoes an oxidative
decarboxylation reaction. First: isocitrate is oxidized Yielding a pair of electrons Associated with a proton as a
hydrogen atom Reduces NAD+ to NADH.
Reaction 3: The First Oxidation
Second: oxidized intermediate is decarboxylated
Central carbon atom splits off to form CO2
Yields a five-carbon molecule α-ketoglutarate
Reaction 4: The Second Oxidation α-ketoglutarate is decarboxylated Looses a CO2
CoEnzyme A is attached Forms succinyl-CoA Two electrons are extracted Associated with a proton as a hydrogen
atom Reduce another molecule of NAD+ to
NADH.
Reaction 5: Substrate-Level Phosphorylation Linkage between the four-carbon
succinyl group & CoA is a high-energy bond.
Bond is cleaved Energy released drives phosphorylation
of GDP, forming GTP. GTP is readily converted into ATP, Succinate 4-carbon fragment that
remains
Reaction 6: Third Oxidation
Succinate is oxidized to fumarate FAD+ is electron acceptor. FAD+ remains in a part of the inner
mitochondria membrane FADH2 (reduced) is used in
electron transport chain in the membrane
Reactions 7 & 8: Regeneration of Oxaloacetate. A water molecule is added to fumarate, Forms malate Malate is then oxidized Yields oxaloacetate a four-carbon
molecule Two electrons Associated with a proton as a hydrogen Reduce a molecule of NAD+ to NADH.
Reactions 7 & 8 : Regeneration of Oxaloacetate.
Oxaloacetate Molecule that began the cycle Combines with another two-carbon
acetyl group from acetyl-CoA Reinitiate the cycle.
Fig. 9-12-1
Acetyl CoA
Oxaloacetate
CoA—SH
1
Citrate
Citricacidcycle
Fig. 9-12-2
Acetyl CoA
Oxaloacetate
Citrate
CoA—SH
Citricacidcycle
1
2
H2O
Isocitrate
Fig. 9-12-3
Acetyl CoA
CoA—SH
Oxaloacetate
Citrate
H2O
Citricacidcycle
Isocitrate
1
2
3
NAD+
NADH
+ H+
-Keto-glutarate
CO2
Fig. 9-12-4
Acetyl CoA
CoA—SH
Oxaloacetate
Citrate
H2O
IsocitrateNAD+
NADH
+ H+
Citricacidcycle
-Keto-glutarate
CoA—SH
1
2
3
4
NAD+
NADH
+ H+SuccinylCoA
CO2
CO2
Fig. 9-12-5
Acetyl CoA
CoA—SH
Oxaloacetate
Citrate
H2O
IsocitrateNAD+
NADH
+ H+
CO2
Citricacidcycle
CoA—SH -Keto-
glutarate
CO2NAD+
NADH
+ H+SuccinylCoA
1
2
3
4
5
CoA—SH
GTP GDP
ADP
P iSuccinate
ATP
Fig. 9-12-6
Acetyl CoA
CoA—SH
Oxaloacetate
H2O
CitrateIsocitrate
NAD+
NADH
+ H+
CO2
Citricacidcycle
CoA—SH -Keto-
glutarate
CO2NAD+
NADH
+ H+
CoA—SH
P
SuccinylCoA
i
GTP GDP
ADP
ATP
Succinate
FAD
FADH2
Fumarate
1
2
3
4
5
6
Fig. 9-12-7
Acetyl CoA
CoA—SH
Oxaloacetate
Citrate
H2O
IsocitrateNAD+
NADH
+ H+
CO2
-Keto-glutarate
CoA—SH
NAD+
NADH
SuccinylCoA
CoA—SH
PP
GDPGTP
ADP
ATP
Succinate
FAD
FADH2
Fumarate
CitricacidcycleH2O
Malate
1
2
5
6
7
i
CO2
+ H+
3
4
Fig. 9-12-8
Acetyl CoA
CoA—SH
Citrate
H2O
IsocitrateNAD+
NADH
+ H+
CO2
-Keto-glutarate
CoA—SH
CO2NAD+
NADH
+ H+SuccinylCoA
CoA—SH
P i
GTP GDP
ADP
ATP
Succinate
FAD
FADH2
Fumarate
CitricacidcycleH2O
Malate
Oxaloacetate
NADH
+H+
NAD+
1
2
3
4
5
6
7
8
Krebs Cycle 2 pyruvate from glycolysis 6 CO2 molecules 2 ATP molecules 10 electron carriers 8 NADH molecules 2 FADH2
Figure 9.16b 2 FADH26 NADH
CITRICACID
CYCLE
PYRUVATEOXIDATION2 Acetyl CoA
+ 2 ATP
2 NADH
Glycolysis & the Krebs cycle
produced a large amount of electron carriers.
These carriers enter the electron transport chain
Help produce ATP
Electron transport chain Energy captured by NADH is not
harvested all at once. Transferred directly to oxygen 2 electrons carried by NADH are
passed along the electron transport chain if oxygen is present.
Oxidative phosphorylation Formation of ATP 1. Electron transport chain Series of molecules embedded in
the inner membranes of mitochondria.
Electrons are delivered at the top of the chain
Oxygen captures them at the bottom
Electron transport chain Large protein complexes Smaller mobile proteins Smaller lipid molecule called
ubiquinone (Q)
Fig. 9-13
NADH
NAD+2FADH2
2 FADMultiproteincomplexesFAD
Fe•S
FMN
Fe•S
Q
Fe•S
Cyt b
Cyt c1
Cyt c
Cyt a
Cyt a3
IV
Fre
e en
erg
y (G
) r e
lat i
ve t
o O
2 (
kcal
/mo
l)
50
40
30
20
10 2
(from NADHor FADH2)
0 2 H+ + 1/2 O2
H2O
e–
e–
e–
Electrons move towards a more electronegative carrier
Electrons move down an electron gradient
This flow of electron creates the active transport of protons out into the matrix
2. Chemiosmosis Protons diffuse back into the
matrix through a proton channel It is coupled to ATP synthesis
Electron transport chain Carbon monoxide & cyanide affect
the electron transport in the mitochondria
Shuts down the production of ATP Cell dies as does the organism
Fermentation Anaerobic conditions H atoms (NADH) are donated to
organic compounds Regenerates NAD+
Figure 9.17a2 ADP + 2 P i
NAD+
+ 2 H+
GLYCOLYSISGlucose
2 ATP
22
2 Ethanol 2 Acetaldehyde
2 Pyruvate
(a) Alcohol fermentation
2 CO2NADH
Figure 9.17b2 ADP + 2 P i
NAD+
+ 2 H+
GLYCOLYSISGlucose
2 ATP
22
Lactate
(b) Lactic acid fermentation
NADH
2 Pyruvate
2
Proteins and fats Other organic
molecules are an important source of energy.
Proteins First are broken down to amino
acids Each amino acid undergoes a
process called deamination. Removal of the nitrogen containing
side group After a series of reactions the
carbon groups enter the either glycolysis or the krebs cycle
Fats Fats are broken down to FA &
glycerol Each FA undergoes β oxidation Conversion of the FA to several
acetyl groups These groups combine with
coenzyme A to make acetyl-CoA
Regulation Control of the glucose catabolism Occurs at 3 key points 1. Control point in glycolysis Enzyme phosphofructokinase Catalyzes the conversion of
fructose 6-phosphate to fructose 1,6 bisphosphate.
Regulation High levels of ATP
inhibit phosphofructokinase
ADP & AMP activate the enzyme
Low levels of citrate also activate the enzyme
Regulation 2. Pyruvate dehydrogenase Enzyme that removes CO2 from
pyruvate. High levels of NADH will inhibit its
action
Regulation 3. High levels of ATP inhibit the
enzyme citrate synthetase Enzyme that starts the Krebs cycle Combines Acetyl-CoA with
oxaloacetate to make citrate
Evolution Krebs cycle & ETC function only in
aerobic conditions Glycolysis occurs in both Early bacteria used only glycolysis to
make ATP before O2
All kingdoms of life use glycolysis Occurs outside the mitochondria Indicates mitochondria developed later.