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The Krebs Cycle - Advanced
Douglas Wilkin, Ph.D.
Barbara Akre
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Printed: January 22, 2015
AUTHORS
Douglas Wilkin, Ph.D.
Barbara Akre
www.ck12.org
C HAPTER
Chapter 1. The Krebs Cycle - Advanced
1 The Krebs Cycle - Advanced
• Relate the history of oxygen in the atmosphere to the evolution of photosynthesis, aerobic respiration, mitochondria, and life on earth.
• Describe the fate in eukaryotic cells of the pyruvate molecules produced by glycolysis if oxygen is present.
• Recognize that for most organisms, if oxygen is present, the products of glycolysis enter the mitochondria for
stage 2 of cellular respiration - the Krebs Cycle.
• Trace carbon and hydrogen atoms through the Krebs Cycle.
• Analyze the importance of the Krebs Cycle to cellular respiration by following the pathway taken by chemical
energy.
What type of acid do these fruits contain?
Citric acid. Citric acid is also the first product formed in the Krebs cycle, and therefore this acid occurs in the
metabolism of virtually all living things.
Aerobic Respiration
Enticing clues - volcanic gases, vast iron ore sediments, and bubbles of ancient air trapped in amber –suggest
dramatic changes during the history of earth’s atmosphere. Correlating these clues with the fossil record leads to
two major conclusions: that early life evolved in the absence of oxygen, and that oxygen first appeared between
2 and 3 billion years ago ( Figure 1.1) because of photosynthesis by the blue green bacteria, cyanobacteria. The
chemistry of cellular respiration reflects this history. Its first stage, glycolysis, is universal and does not use oxygen.
Absolutely dependent on oxygen gas, we find it difficult to imagine that its appearance must have been disastrous
for the anaerobic organisms that evolved in its absence. But oxygen is highly reactive, and at first, its effect on
evolution was so negative that some have named this period the “oxygen catastrophe.” However, as oxygen gradually
formed a protective ozone layer, life rebounded. After the first organisms evolved to use oxygen to their advantage,
the diversity of aerobic organisms exploded. According to the Theory of Endosymbiosis, engulfing of some of
these aerobic bacteria led to eukaryotic cells with mitochondria, and multicellularity, the evolution of multicellular
eukaryotic organisms, followed. Today, we live in an atmosphere which is 21% oxygen, and most of life follows
glycolysis with the last two, aerobic stages of cellular respiration.
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FIGURE 1.1
Oxygen has increased in the atmosphere
throughout the history of the earth. Note
the logarithmic scale, which indicates
great increases after first photosynthesis
(in bacteria) and then land plants evolved.
Related geological events: A = no oxidized iron; B = oxidized iron bands in
seabed rock - evidence for O2 in the
oceans; C = oxidized iron bands on land
and ozone layer formation- evidence for
O2 in the atmosphere.
Recall the purpose of cellular respiration: to release energy from glucose to make ATP, the universal molecule
of energy for cellular work. The following equation describes the overall process, although it summarizes many
individual chemical reactions.
Once again, the first stage of this process, glycolysis, is ancient, universal, and anaerobic. In the cytoplasm of most
cells, glycolysis breaks each 6-carbon molecule of glucose into two 3-carbon molecules of pyruvate. Chemical
energy, which had been stored in the now broken bonds, is transferred to 2 ATP and 2 NADH molecules.
The fate of pyruvate depends on the species and the presence or absence of oxygen. If oxygen is present to drive
subsequent reactions, pruvate enters the mitochondrion, where the Krebs Cycle (Stage 2) and electron transport
chain (Stage 3) break it down and oxidize it completely to CO2 and H2 O. The energy released builds many more
ATP molecules, though of course some is lost as heat. Let’s explore the details of how mitochondria use oxygen to
make more ATP from glucose by aerobic respiration.
The Krebs Cycle: Capturing Energy from Pyruvate
Aerobic respiration begins with the entry of the product of glycolysis, pyruvate, into the mitochondria. For each
initial glucose molecules, two pyruvate molecules will enter the mitochondria. Pyruvate, however, is not the
molecule that enters the Krebs cycle. Prior to entry into this cycle, pyruvate must be converted into a 2-carbon
acetyl-CoenzymeA (acetyl-CoA) unit. The conversion of pyruvate into acetyl-CoA is referred to as the pyruvate
dehydrogenase reaction. It is catalyzed by the pyruvate dehydrogenase complex. This process produces one NADH
electron carrier while releasing a CO2 molecule. This step is also known as the link reaction or transition step, as
it links glycolysis and the Krebs cycle. Of course, as two pyruvates result from glycolysis, two acetyl-CoAs are
produced as are 2 NADH molecules.
1. Within the mitochondria, each pyruvate is broken apart and combined with a coenzyme known as CoA to form
a 2-carbon molecule, Acetyl-CoA, which can enter the Krebs Cycle. A single atom of carbon (per pyruvate)
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Chapter 1. The Krebs Cycle - Advanced
FIGURE 1.2
After glycolysis, two 3-carbon pyruvates
enter the mitochondrion, where they
are converted to two 2-carbon acetylCoenzymeA (CoA) molecules.
Acetyl-
CoA then enters the Krebs Cycle. Note
that the carbons removed become carbon
dioxide, accounting for two of the six such
end products of glucose oxidation. The
energy released by this breakdown is carried by NADH.
is “lost” as carbon dioxide. The energy released in this breakdown is captured in two NADH molecules. See
Figure 1.2. Fatty acids can also break down into Acetyl-CoA. By this means, lipids, like fats, can be “burned”
to make ATP using the Krebs Cycle.
2. The Krebs Cycle ( Figure 1.3) begins by combining each Acetyl-CoA with a four-carbon carrier molecule to
make a 6-carbon molecule of citric acid (or citrate, its ionized form). For this reason, the Krebs Cycle, named
for a scientist who worked out its details, is also called the Citric Acid Cycle.
3. The cycle carries citric acid through a series of chemical reactions which gradually release energy and capture
it in several carrier molecules. For each Acetyl-CoA which enters the cycle, 3 NAD+ are reduced to NADH,
one molecule of FAD (another temporary energy carrier) is reduced to FADH2 , and one molecule of ATP
(actually a precursor, GTP, guanine triphosphate) is produced. Study Figure 1.3 to locate each of these
energy-capturing events.
4. Note what happens to carbon atoms (black dots in Figure 1.3). For each 2-carbon Acetyl-CoA which enters
the cycle, two molecules of carbon dioxide are released, completing the breakdown of the original 6-carbon
glucose molecule. The final step regenerates the original 4-carbon molecule which began the cycle, so that
another Acetyl-CoA can enter the cycle.
In summary, the Krebs Cycle completes the breakdown of glucose which began with glycolysis. Its chemical
reactions oxidize all six of the original carbon atoms to CO2 , and capture the energy released in 2 ATP, 6 NADH,
and 2 FADH2 . These energy carriers join the 2 ATP and 2 NADH produced in glycolysis and the 2 NADH produced
in the conversion of 2 pyruvates to 2 Acetyl-CoA molecules.
At the conclusion of the Krebs Cycle, glucose is completely broken down, yet only four ATP have been produced.
Moreover, although oxygen is required to drive the Krebs Cycle, the cycle’s chemical reactions do not themselves
consume O2 . The conclusion of cellular respiration, stage 3, produces the majority of the ATP.
The Krebs cycle is reviewed at http://www.youtube.com/watch?v=juM2ROSLWfw (17:47).
MEDIA
Click image to the left or use the URL below.
URL: http://www.ck12.org/flx/render/embeddedobject/265
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FIGURE 1.3
The Krebs cycle completes the breakdown of glucose begun in glycolysis. If oxygen is present, pyruvate
enters the mitochondria and is converted to AcetylCoA. AcetylCoA enters the cycle by combining with 4-carbon
oxaloacetate. Study the diagram to confirm that each turn of the cycle (two for each glucose) stores energy in 3
NADH+H+ , one FADH2 , and one ATP (from GTP), and releases 2 CO2 . The Krebs cycle is also known as the
Citric Acid Cycle or the tricarboxylic acid cycle (TCA cycle).
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Chapter 1. The Krebs Cycle - Advanced
Vocabulary
• Citric Acid Cycle: Stage 2 of aerobic cellular respiration; a series of chemical reactions which completes the
breakdown of glucose begun in stage 1, releasing more chemical energy and producing carbon dioxide; also
called the Krebs cycle.
• electron transport chain: Series of electron-transport molecules that pass high-energy electrons from molecule
to molecule and capture their energy.
• FADH2 : Flavin adenine dinucleotide; an energy carrier molecule produced during the Krebs cycle of aerobic
cellular respiration.
• glycolysis: The process of “splitting glucose”; stage 1 of aerobic cellular respiration and also the basis of
anaerobic respiration; splits glucose into two 3-carbon pyruvate molecules, producing 2 (net) ATP.
• Krebs cycle: Stage 2 of aerobic cellular respiration; a series of chemical reactions which completes the
breakdown of glucose begun in stage 1, releasing more chemical energy and producing carbon dioxide; also
called the Citric Acid Cycle.
• multicellularity: Refers to organisms that consist of more than one cell, in contrast to single-cell organisms;
this is characteristic of most eukaryotes.
• ozone layer: A layer in Earth’s atmosphere containing relatively high concentrations of ozone; absorbs a high
percentage of the Sun’s medium-frequency ultraviolet light.
• pyruvate: The 3-carbon product of glycolysis; also known as pyruvic acid.
• Theory of Endosymbiosis: Theory that proposes that eukaryotic organelles, such as mitochondria, evolved
from ancient, free-living prokaryotes that invaded other prokaryotic cells.
Summary
• Oxygen produced by the first photosynthetic organisms was probably toxic to early anaerobic life forms, but
later organisms evolved a way to harness the power of oxygen to make ATP.
• In eukaryotic cells, if oxygen is present, the pyruvate molecules produced by glycolysis in the cytoplasm enter
the mitochondria for further breakdown and energy release. The Krebs Cycle harnesses the energy which
remains in pyruvate after glycolysis.
• The Krebs Cycle removes energy from citric acid in small steps, storing it in diverse energy carrier molecules:
ATP, NADH and FADH2 .
• The Krebs Cycle produces two molecules of CO2 per Acetyl-CoA, completing the breakdown of glucose.
Explore More I
Use these resources to answer the questions that follow.
• The Citric Acid Cycle at http://virtuallabs.stanford.edu/other/biochem/TCA.swf .
1. Where does the Krebs cycle occur in the cell?
2. What is the first product of this cycle?
3. How many reactions does it take to complete the cycle?
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Explore More II
• Krebs Cycle at http://johnkyrk.com/krebs.html .
Review
1. Explain why the appearance of oxygen in the atmosphere between two and three billions of years ago was
both “good news and bad news” for life on Earth.
2. In eukaryotic cells when oxygen is present, what is the fate of the pyruvate produced in glycolysis?
3. Define the Krebs cycle.
4. Trace the six carbon atoms originally from acetyl-CoA through the Krebs Cycle. Trace the flow of energy
from the pyruvates produced in glycolysis through the Krebs Cycle.
5. How many energy carriers are produced during the Krebs cycle per acetyl-CoA?
References
1. User:Tameeria/Wikipedia. . Public Domain
2. Joy Sheng. . CC BY-NC 3.0
3. Laura Guerin. . CC BY-NC 3.0
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