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Cellular Energy
• In order to sustain life (steady state), cells constantly
expend energy in the form of ATP hydrolysis
– the hydrolysis of ATP yields a molecule of ADP
(adenosine diphosphate) and a Phosphate group
• ATP → ADP + P
• Following ATP hydrolysis, the cell synthesizes new
molecules of ATP using ADP and P
– ADP + P → ATP
– “recycling energy”
– cells use the energy stored in the covalent bonds of
monosaccharides, fatty acids and amino acids
as an energy source (fuel) to resynthesize ATP
Fuels for ATP
Synthesis
Cellular Respiration
• Most cells of the body use glucose (in the presence of
O2 that we inhale) as fuel source to synthesize
molecules of ATP in a process called cellular
respiration
• The products include molecules of carbon dioxide that
we exhale, and water
• C6H12O6 + 6O2 + 38 ADP +38 P Æ 6H2O + 6CO2 + 38 ATP
– note that the number of atoms in the reactants
equal the number of atoms in the products
Cellular Respiration
Cellular Respiration
• The process of cellular respiration is divided into 3
sequential phases
– Glycolysis
• occurs in the cytoplasm of a cell
– Krebs cycle (Citric acid cycle)
• occurs in the mitochondrial matrix
– The electron transport chain
• occurs across the inner mitochondrial membrane
–between the mitochondrial matrix and the
intermembrane space
Cellular
Respiration
Overview
Cellular Respiration
• During the phases of glycolysis and the Krebs cycle, a
single molecule of glucose is gradually broken apart in
20 sequential biochemical reactions into different
carbohydrate intermediates
– only 4 molecules of ATP are synthesized during
these phases by the energy released from the
breaking of covalent bonds of the carbohydrate
intermediates
• As the glucose molecule is broken apart, the 12
hydrogen atoms are gradually removed and used to
create a large H+ gradient between the
intermembrane space and the matrix of the
mitochondria
– the H+ gradient is used as an energy source by the
electron transport chain to synthesize the remaining
34 molecules of ATP
Glycolysis Overview
• Glycolysis = sugar breaking
• The first 7 biochemical reactions of cellular respiration
are catalyzed by 7 different enzymes in the cytoplasm
• Starts with 1 molecule of glucose (6 carbons) and
ends with 2 molecules of pyruvic acid (3 carbons x 2 =
6 carbons)
Glycolysis
• During glycolysis:
– Energy is invested as 2 ATPs are hydrolyzed during
steps 1 and 3
– One 6 carbon carbohydrate intermediate is split
(lysis) into two 3 carbon carbohydrate intermediates
during step 4
– each of the 3 carbon carbohydrate intermediates
molecules lose a H (becoming oxidized) which is
accepted by a coenzyme called NAD+ (becoming
reduced to NADH) during step 5
• NADH carries H to the mitochondrial matrix to
build the H+ gradient
– 4 molecules of ATP are synthesized
• 2 during step 6
• 2 during step 7
Glycolysis
Products of Glycolysis
• The products of glycolysis are:
– 2 molecules of ATP
• 4 are synthesized, but 2 are hydrolyzed at the
beginning of glycolysis
– 2 molecules of pyruvic acid (3 carbon molecule)
– 2 molecules of NADH
• Only 2 of 38 molecules of ATP are synthesized during
glycolysis
Pyruvic Acid
• The presence or absence of O2 in the cell determines
how the cell will use the 2 molecules of pyruvic acid at
the end of glycolysis
– If O2 is present pyruvic acid will be used in the
process of aerobic respiration
• 36 more molecules of ATP are synthesized as
cellular respiration continues through the Krebs
cycle and the electron transport chain
– If O2 is absent the pyruvic acid will be used in the
process of anaerobic respiration (fermentation)
• produces no more ATP
Anaerobic Fermentation
• In the absence of O2 (oxygen debt), the 2 molecules of
pyruvic acid from the end of glycolysis are converted
into 2 molecules of lactic acid
• Anaerobic fermentation most commonly occurs in
active skeletal muscle cells when they use O2 faster
than it can be delivered by the respiratory and
circulatory systems
• The accumulation of lactic acid causes:
– muscle proteins to partially denature
• leading to muscle weakening (fatigue)
– muscle soreness
Aerobic Respiration
• In the presence of O2, the 2 molecules of pyruvic acid
from the end of glycolysis are transported into the
mitochondrial matrix
• Each molecule of pyruvic acid is then converted into a
molecule of Acetyl Coenzyme A (Acetyl CoA)
– required step between glycolysis and the Krebs
cycle
2 Pyruvic Acid → 2 Acetyl CoA
During the conversion of each of the 2 molecules of
pyruvic acid to Acetyl CoA the following occurs:
• Decarboxylation (CO2 is removed) of pyruvic acid
making acetic acid (2 carbons)
• One H is removed from acetic acid (oxidized) by NAD+
(reduced to NADH) and further contributes to the H+
gradient
• Coenzyme A in the mitochondrial matrix is added to
the acetic acid to make acetyl CoA
During this step the products are:
– 2 molecules of CO2
– 2 molecules of NADH
– 2 molecules of Acetyl CoA
• used in the Krebs Cycle
Krebs Cycle (Citric Acid Cycle)
• A series of 10 biochemical reactions which begins and
ends (cyclic) with a molecule of citric acid
• Each acetic acid (2 carbons) is combined with a
molecule of oxaloacetic acid in the mitochondrial
matrix (4 carbons) to make citric acid (6 carbons)
during step 1
• Each citric acid is then decarboxylated twice (steps 4
and 6) and oxidized (H is removed during steps 3, 5, 8
and 10) as it is converted into different carbohydrate
intermediates
– energy released from the hydrolysis of bonds is
used to synthesize ATP during step 7
– NAD+ (steps 3, 5 and 10) and FAD (step 8) are
reduced to NADH and FADH2 and further
contributes to the H+ gradient in the mitochondria
Krebs
Cycle
Products of Krebs Cycle
• The reactions of the Krebs cycle produce:
– 3 molecules of NADH
– 1 molecule of FADH2
– 2 molecules of CO2
– 1 molecule of ATP
– 1 molecule of oxaloacetic acid
• Since each molecule of glucose yields two molecules
of acetyl CoA, 2 Krebs cycles yield:
– 6 NADH
– 2 FADH2
– 4 CO2
– 2 ATP
– 2 oxaloacetic acid
• reenter the Krebs cycle of reactions after
combined with another acetic acid
Products of Glycolysis → Krebs Cycle
• 4 ATP
– 2 (net) from glycolysis
– 2 from Krebs
• 10 NADH (10 H from original glucose molecule)
– 2 from glycolysis
– 2 from (2) Pyruvic Acid → (2)Acetyl CoA
– 6 from Krebs
• 2 FADH2 (2 H from original glucose molecule)
– 2 from Krebs
• 6 CO2 (6 C from original glucose molecule)
– 2 from (2) Pyruvic Acid → (2)Acetyl CoA
– 4 from Krebs
CO2
NAD
ATP
NADH
ADP
ATP
3C
Pyruvic
Acid
ADP
ADP
2C
Acetyl
CoA
CO2
ATP
NADH
NADH
NAD
2C
Acetate
+
OAA
4C
NAD
6C
Citric
Acid
CO2
NADH
NAD
ADP
FADH2NADH
FAD NAD
4C
OAA
CoA
6C
Glucose
CO2
NADH
NADH
ATP
ATP
ADP
ATP
ADP
3C
Pyruvic
Acid
CO2
ADP
NAD
NADH
GLYCOLYSIS
CYTOPLASM
NAD
2C
Acetyl
CoA
CoA
2C
Acetate
+
OAA
4C
6C
Citric
Acid
CO2
NADH
NAD
ATP
ADP
ATP
KREBS (CITRIC ACID) CYCLE
MITOCHONDIAL MATRIX
FADH2NADH
FAD NAD
4C
OAA
Electron Transport Chain
• A group of 3 integral proteins and 2 membrane
coenzymes associated with the inner mitochondrial
membrane called the electron transport chain (ETC)
creates a H+ gradient between the intermembrane
space and the matrix of the mitochondria using the H
of from NADH and FADH2 that accumulate in the
mitochondrial matrix as products of glycolysis and the
Krebs cycle
• 3 (integral) enzyme complexes of the ETC remove the
H from NADH and FADH2 (oxidized back to NAD+ and
FAD+) in the matrix
ETC and Oxidative Phosphorylation
FADH2
FAD+
NADH and the Electron Transport Chain
• NADH is oxidized by Enzyme complex 1 of the ETC
• The H that is removed by Enzyme complex 1 is split
into an electron (e-) and a proton (H+)
• The e- is passed from the beginning to the end of the
ETC and energizes the 1st, 2nd and 3rd Enzyme
complexes along the way
– Once energized, each enzyme complex pumps a
free proton from the mitochondrial matrix into the
intermembrane space (3 total)
FADH2 and the Electron Transport Chain
• FADH2 is oxidized by Enzyme complex 2 of the ETC
• The H that is removed by Enzyme complex 2 is split
into an electron (e-) and a proton (H+)
• The e- is passed to the end of the ETC and energizes
the 2nd and 3rd Enzyme complexes along the way
– Once energized, each enzyme complex pumps a
free proton from the mitochondrial matrix into the
intermembrane space (2 total)
Proton (H+) gradient
• The movement of protons from the matrix into the
intermembrane space creates a high H+ (pH = 7)
concentration in the intermembrane space and a low
H+ (pH = 8) concentration in the matrix
– this proton gradient becomes the source of energy
used by the mitochondria to synthesize ATP, which
is released as H+ diffuse from the intermembrane
space back into the matrix
• The oxidation of NADH contributes more (pumps 3 H+)
to the proton gradient than FADH2 (pumps 2 H+)
ATP Synthase
• ATP synthase is an integral membrane protein in the
inner mitochondrial membrane that has 2 functions:
– it acts as a H+ channel
• allows H+ to diffuse down its gradient from the
intermembrane space into the matrix
– it acts as an enzyme
• uses the energy that is released by the diffusion
of H+ to synthesize ATP from ADP and P
• This type of ATP synthesis is called oxidative
phosphorylation because, this process requires the
oxidation of NADH and FADH2
ATP Synthesis During Oxidative Phosphorylation
• Because the oxidation of NADH contributes more to
the proton gradient than the oxidation of FADH2, more
ATP is synthesized from NADH than FADH2
• On average, for each NADH that is oxidized 3
molecules of ATP are synthesized
– 10 NADH x 3 ATP = 30 ATP
• On average, for each FADH2 that is oxidized 2
molecules of ATP are synthesized
– 2 FADH2 x 2 ATP = 4 ATP
• 34 of the 38 molecules of ATP are synthesized by
oxidative phosphorylation
Formation of Water
• After the electrons arrive to the last enzyme complex
of the ETC they are transferred to atoms of oxygen in
the mitochondrial matrix
– this makes oxygen especially negative
• In the matrix, these oxygen atom are combined with
the H+ that have diffused back into the matrix from the
intermembrane space to form water (H2O)
– the protons become “reunited” with their electron