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Krebs Cycle and Oxidative phosphorylation

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Nikoleta Milanovic

on 18 April 2017

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Transcript of Krebs Cycle and Oxidative phosphorylation

The citric acid cycle
(CAC) also known as the
tricarboxylic acid (TCA) cycle
the Krebs cycle
is a series of chemical reactions used by all aerobic organisms to release stored energy through the
oxidation of acetyl-CoA
derived from carbohydrates, fats and proteins into
carbon dioxide
chemical energy
in the form of
adenosine triphosphate, (ATP.)
In addition, the cycle provides precursors of certain
amino acids
as well as the
reducing agent NADH
that is used in numerous other biochemical reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest established components of cellular metabolism and may have originated abiogenically
The reactions of the cycle convert three equivalents of nicotinamide adenine dinucleotide (NAD+) into
three equivalents of reduced NAD+ (NADH)
, one equivalent of flavin adenine dinucleotide (FAD) into
one equivalent of FADH2
, and one equivalent each of guanosine diphosphate (GDP) and inorganic phosphate (Pi) into
one equivalent of guanosine triphosphate (GTP)
. The NADH and FADH2 generated by the citric acid cycle are in turn used by t
he oxidative phosphorylation pathway
to generate energy-rich adenosine triphosphate (
Krebs Cycle and Oxidative phosphorylation
Photosynthesis, absorption
Organic substances
(amino acids, fatty acids, polysaccharides)
Sun, water, earth
Animal cell
Plant cell
Degradation of amino and fatty acids
Degradation of glucose
Degradation of fatty acids
Degradation of amino acids
Only in cases of starvation!!!
Degradation of glucose
The end products-
Piruvic acid
Oxidation of organic substances
"Cellular respiration"

Several of the components and reactions of the citric acid cycle were established in the 1930s by the research of the
Albert Szent-Györgyi
, who received the Nobel Prize in Physiology or Medicine in 1937 specifically for his discoveries pertaining to
fumaric acid
; a key component of the cycle. The citric acid cycle itself was finally identified in 1937 by
Hans Adolf Krebs
William Arthur Johnson
while at the University of Sheffield, for which the former received the Nobel Prize for Physiology or Medicine in 1953.
eukaryotic cells
, the citric acid cycle occurs in the
matrix of the mitochondrion
. In
prokaryotic cells
, such as bacteria which lack mitochondria, the TCA reaction sequence is performed in the
with the proton gradient for ATP production being across the cell's surface (plasma membrane) rather than the inner membrane of the mitochondrion.
Where does it happen?
The name of this metabolic pathway is derived from
citric acid
(a type of tricarboxylic acid, often called citrate, as the ionized form predominates at biological pH) that is consumed and then regenerated by this sequence of reactions to complete the cycle. In addition, the cycle consumes acetate (in the form of

) and
, reduces
, and produces
carbon dioxide

as a waste byproduct. The NADH generated by the TCA cycle is fed into the
oxidative phosphorylation
(electron transport) pathway. The net result of these two closely linked pathways is the oxidation of nutrients to produce usable chemical energy in the form of
Products of the cycle

CH3C(=O)C(=O)O−+ HSCoA + NAD+ CH3C(=O)SCoA + NADH + CO2



One of the primary sources of acetyl-CoA is from the
breakdown of sugars by glycolysis
which yield
that in turn is decarboxylated by the enzyme
pyruvate dehydrogenase
according to the following reaction scheme:
The product of this reaction, acetyl-CoA, is the starting point for the citric acid cycle. Acetyl-CoA may also be obtained from the
oxidation of fatty acids
coenzyme A
Products of the first turn of the cycle are
: one GTP (or ATP), three NADH, one QH2, two CO2.

Because two acetyl-CoA molecules are produced from each glucose molecule,
two cycles are required per glucose molecule
. Therefore, at the end of two cycles, the products are: two GTP, six NADH, two QH2, and four CO2
What is mitochondrion and how does it look like?
The theoretical maximum yield of ATP through oxidation of one molecule of glucose in glycolysis, citric acid cycle, and oxidative phosphorylation is
(assuming 3 molar equivalents of ATP per equivalent NADH and 2 ATP per FADH2). In

two equivalents of NADH are generated in glycolysis
, which takes place in the
. Transport of these two equivalents into the mitochondria
consumes two equivalents of ATP
, thus reducing the net production of ATP to
. Furthermore, inefficiencies in oxidative phosphorylation due to leakage of protons across the mitochondrial membrane and slippage of the ATP synthase/proton pump commonly reduces the ATP yield from NADH and FADH2 to less than the theoretical maximum yield. The observed yields are, therefore, closer to
~2.5 ATP per NADH
~1.5 ATP per FADH2
, further reducing the total net production of ATP to approximately
. An assessment of the total ATP yield with newly revised proton-to-ATP ratios provides an estimate of
29.85 ATP per glucose molecule.
Oxidative phosphorylation
Oxidative phosphorylation (or OXPHOS in short) is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing energy which is used to reform ATP. In most
, this takes place inside mitochondria. Almost
all aerobic organisms
carry out oxidative phosphorylation. This pathway is probably so pervasive because it is a highly efficient way of releasing energy, compared to alternative
fermentation processes
such as anaerobic
During oxidative phosphorylation, electrons are transferred from
electron donors
electron acceptors
such as
, in
redox reactions
. These redox reactions release energy, which is used to form ATP.
Where does it happen?
, these redox reactions are carried out by a series of protein complexes within the
inner membrane of the cell's mitochondria
, whereas, in prokaryotes, these proteins are located in the cells' intermembrane space. These linked sets of proteins are called electron transport chains. In eukaryotes, five main protein complexes are involved, whereas in prokaryotes many different enzymes are present, using a variety of electron donors and acceptors.
The energy released by electrons flowing through this electron transport chain is used to transport protons across the inner mitochondrial membrane, in a process called
electron transport
. This generates potential energy in the form of a pH gradient and an electrical potential across this membrane. This store of energy is tapped by allowing protons to flow back across the membrane and down this gradient, through a
large enzyme called ATP synthase
; this process is known as
. This enzyme uses this energy to generate ATP from adenosine diphosphate (ADP), in a
phosphorylation reaction
. This reaction is driven by the
proton flow
, which forces the rotation of a part of the enzyme;
the ATP synthase is a rotary mechanical motor.
Although oxidative phosphorylation is a
vital part of metabolism
, it produces reactive oxygen species such as
hydrogen peroxide
, which lead to propagation of
free radicals
, damaging cells and contributing to disease and, possibly, aging . The enzymes carrying out this metabolic pathway are also the
target of many drugs and poisons
that inhibit their activities. It is the terminal process of cellular respiration in eukaryotes and accounts for
high ATP(Adenosine triphosphate) yield
Cons of the process
1 Before entering the Krebs cycle, pyruvate is converted to
A) glucose.
B) H2O and CO2.
C) acetic acid.
D) acetyl-CoA.
E) oxaloacetate.

2 A single "turn" of the Krebs cycle will yield
A) 1 ATP, 2 NADH, and 1 FADH2.
B) 1 ATP, 2 NADH, and 2 FADH2.
C) 1 ATP, 3 NADH, and 1 FADH2.
D) 2 ATP, 2 NADH, and 2 FADH2.
E) 2 ATP, 3 NADH, and 2 FADH2.

3 The initial reaction of the Krebs cycle involves the addition of a
A) 2-carbon molecule to a 4-carbon molecule.
B) 2-carbon molecule to a 5-carbon molecule.
C) 2-carbon molecule to a 6-carbon molecule.
D) 3-carbon molecule to a 4-carbon molecule.
E) 3-carbon molecule to a 5-carbon molecule.

4 The Krebs cycle occurs in the mitochondrion.
A) True
B) False

5 A single "turn" of the Krebs cycle involves four different decarboxylation reactions.
A) True
B) False

Quiz Time!
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