Explain why citric acid cycle can't operate in the absence of oxygen?

Cooper is right... Once the ETC stops oxidizing NADH to NAD+ there is no longer any NAD+ available for the Krebs cycle to reduce back to NADH and the cycle comes to a halt. Therefore, the Krebs cycle is actually regulated by the availability of NAD+ It is true that the Fermentation process an contribute to NAD+ regeneration but remember that under anaerobic condition most of the cell's pyruvate is being sent to the Fermentation pathway... and even when NAD+ is regenerated during Fermentation, there will be much less Pyruvate (I'm trying to avoid words like "none") entering the Kreb's Cycle. All this being said, yes technically it can but it would not be contributing to the overall goal (ETC) so the ATP production will be significantly less.

Is there a difference between ATP and GTP?

ATP is adenosine triphosphate, or adenine (the DNA base) with a ribose (the sugar) attached which makes it adenosine, then with three phosphate groups added. GTP is all the same stuff, except for Guanine substituted in for Adenine.

Which provides more energy output, 1 ATP molecule or 1 GTP molecule?

The difference between ATP and GTP is not on their energy output, but on their relative abundance in cells. There are far more ATP than GTP in cells to provide energy, because of evolution.

How kerebs found this cycle?

Krebs was working on the problem of finding the chemicals that act as intermediaries in cellular respiration. He discovered that when he added certain chemicals to pigeon breast muscle cells, their oxygen consumption would increase, thus indicating that more respiration reactions were taking place. These chemicals are the same ones we now identify as those making up the Kreb's Cycle. :)

Going from Malate to Oxaloacetic Acid 2 hydrogen ions are hydrolyzed but only one NADH is formed. Where did the other Hydrogen Ion go?

NAD+ needs 2 electrons en 1 proton to make NADH. The oxidation of malate transfers these products to NAD+. There is indeed a remaining H+ ion that is released in the matrix as a proton. That way the charge is kept on both ends of the reaction. This also happens with the other times that NADH is formed (releasing a proton) but there the proton was released beforehand when the carboxyl group was created.

In the picture "Oxidation of pyruvate and citric acid cycle", in step 3 and 4, I saw there are 2 H+ ions produced but I'm not sure where they came from. I think there should be no spare H+ ion in step 3 and 4.

They are not spare, that's the way NAD+ is reduced. Those H+ ions are used in generating proton gradient later for ETC.

I was wondering whether it's necessary to remember the formula of each compound? Thank you! :)

Most basic biology classes, even AP bio don't require you to know the exact structure, although you might want to know their basic structure such as oh this is glucose with a phosphate group attached, this is a molecule with an extra proton, since most questions in that topic will revolve around that.

Can GTP serve the same functions as ATP?

They are both energy carriers and there are even enzymes that will exchange high-energy phosphates among ribonucleotides§. However, these molecules are not interchangeable at a molecular level — most enzymes can only use one or the other as a source of energy. For example, ribosomes use GTP (never ATP) to drive the correct decoding of the codons in mRNA — in contrast, aminoacyl-tRNA synthetases can only use ATP to couple amino acids to the correct tRNA‡. Does that help? §Note: Nucleoside-diphosphate kinases (NDKs) — for details see: https://en.wikipedia.org/wiki/Nucleoside-diphosphate_kinase ‡Note: Khan academy has more about these processes here: https://www.khanacademy.org/science/biology/gene-expression-central-dogma#translation-polypeptides

If using this for CLEP bio should I memorize this cycle and equation?

Having taken the CLEP Biology exam, I would recommend it. You may not come across it, but it can't hurt. I had a few questions regarding this, but I can't remember whether I needed the equation memorized. I still memorized it though, because I would rather know it and not need it than not know it and need it.

Main content

Course: Biology library > Unit 12

Lesson 4: Pyruvate oxidation and the citric acid cycle

The citric acid cycle

Google Classroom

Overview and steps of the citric acid cycle, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle.

Introduction

How important is the citric acid cycle? So important that it has not one, not two, but three different names in common usage today!

The name we'll primarily use here, the citric acid cycle, refers to the first molecule that forms during the cycle's reactions—citrate, or, in its protonated form, citric acid. However, you may also hear this series of reactions called the tricarboxylic acid (TCA) cycle, for the three carboxyl groups on its first two intermediates, or the Krebs cycle, after its discoverer, Hans Krebs.

The first two intermediates of the citric acid cycle are shown below. Each has three carboxyl groups, marked with red boxes. When citrate gains three

H^{+}

ions, so that it no longer has a negative charge, it is called citric acid.

image credit: modified from "Oxidation of pyruvate and citric acid cycle: Figure 2" by OpenStax College, Biology, CC BY 3.0

Whatever you prefer to call it, the citric cycle is a central driver of cellular respiration. It takes acetyl

CoA

—produced by the oxidation of pyruvate and originally derived from glucose—as its starting material and, in a series of redox reactions, harvests much of its bond energy in the form of

NADH

{FADH}_{2}

, and

ATP

molecules. The reduced electron carriers—

NADH

and

{FADH}_{2}

—generated in the TCA cycle will pass their electrons into the electron transport chain and, through oxidative phosphorylation, will generate most of the ATP produced in cellular respiration.

Below, we’ll look in more detail at how this remarkable cycle works.

Overview of the citric acid cycle

In eukaryotes, the citric acid cycle takes place in the matrix of the mitochondria, just like the conversion of pyruvate to acetyl

CoA

. In prokaryotes, these steps both take place in the cytoplasm. The citric acid cycle is a closed loop; the last part of the pathway reforms the molecule used in the first step. The cycle includes eight major steps.

In the first step of the cycle, acetyl

CoA

combines with a four-carbon acceptor molecule, oxaloacetate, to form a six-carbon molecule called citrate. After a quick rearrangement, this six-carbon molecule releases two of its carbons as carbon dioxide molecules in a pair of similar reactions, producing a molecule of

NADH

each time

^{1}

. The enzymes that catalyze these reactions are key regulators of the citric acid cycle, speeding it up or slowing it down based on the cell’s energy needs

^{2}

The remaining four-carbon molecule undergoes a series of additional reactions, first making an

ATP

molecule—or, in some cells, a similar molecule called

GTP

—then reducing the electron carrier

FAD

{FADH}_{2}

, and finally generating another

NADH

. This set of reactions regenerates the starting molecule, oxaloacetate, so the cycle can repeat.

Overall, one turn of the citric acid cycle releases two carbon dioxide molecules and produces three

NADH

, one

{FADH}_{2}

, and one

ATP

GTP

. The citric acid cycle goes around twice for each molecule of glucose that enters cellular respiration because there are two pyruvates—and thus, two acetyl

CoA

s—made per glucose.

Steps of the citric acid cycle

You've already gotten a preview of the molecules produced during the citric acid cycle. But how, exactly, are those molecules made? We’ll walk through the cycle step by step, seeing how

NADH

{FADH}_{2}

, and

ATP

GTP

are produced and where carbon dioxide molecules are released.

Step 1. In the first step of the citric acid cycle, acetyl

CoA

joins with a four-carbon molecule, oxaloacetate, releasing the

CoA

group and forming a six-carbon molecule called citrate.

Step 2. In the second step, citrate is converted into its isomer, isocitrate. This is actually a two-step process, involving first the removal and then the addition of a water molecule, which is why the citric acid cycle is sometimes described as having nine steps—rather than the eight listed here

^{3}

Step 3. In the third step, isocitrate is oxidized and releases a molecule of carbon dioxide, leaving behind a five-carbon molecule—α-ketoglutarate. During this step,

{NAD}^{+}

is reduced to form

NADH

. The enzyme catalyzing this step, isocitrate dehydrogenase, is important in regulating the speed of the citric acid cycle.

Step 4. The fourth step is similar to the third. In this case, it’s α-ketoglutarate that’s oxidized, reducing

{NAD}^{+}

NADH

and releasing a molecule of carbon dioxide in the process. The remaining four-carbon molecule picks up Coenzyme A, forming the unstable compound succinyl

CoA

. The enzyme catalyzing this step, α-ketoglutarate dehydrogenase, is also important in regulation of the citric acid cycle.

image credit: modified from "Oxidation of pyruvate and citric acid cycle: Figure 2" by OpenStax College, Biology, CC BY 3.0

Step 5. In step five, the

CoA

of succinyl

CoA

is replaced by a phosphate group, which is then transferred to

ADP

to make

ATP

. In some cells,

GDP

—guanosine diphosphate—is used instead of

ADP

, forming

GTP

—guanosine triphosphate—as a product. The four-carbon molecule produced in this step is called succinate.

Step 6. In step six, succinate is oxidized, forming another four-carbon molecule called fumarate. In this reaction, two hydrogen atoms—with their electrons—are transferred to

FAD

, producing

{FADH}_{2}

. The enzyme that carries out this step is embedded in the inner membrane of the mitochondrion, so

{FADH}_{2}

can transfer its electrons directly into the electron transport chain.

Step 7. In step seven, water is added to the four-carbon molecule fumarate, converting it into another four-carbon molecule called malate.

Step 8. In the last step of the citric acid cycle, oxaloacetate—the starting four-carbon compound—is regenerated by oxidation of malate. Another molecule of

{NAD}^{+}

is reduced to

NADH

in the process.

Products of the citric acid cycle

Let’s take a step back and do some accounting, tracing the fate of the carbons that enter the citric acid cycle and counting the reduced electron carriers—

NADH

and

{FADH}_{2}

—and

ATP

produced.

In a single turn of the cycle,

two carbons enter from acetyl $CoA$ ‍, and two molecules of carbon dioxide are released;
three molecules of $NADH$ ‍ and one molecule of ${FADH}_{2}$ ‍ are generated; and
one molecule of $ATP$ ‍ or $GTP$ ‍ is produced.

These figures are for one turn of the cycle, corresponding to one molecule of acetyl

CoA

. Each glucose produces two acetyl

CoA

molecules, so we need to multiply these numbers by

2

if we want the per-glucose yield.

Two carbons—from acetyl

CoA

—enter the citric acid cycle in each turn, and two carbon dioxide molecules are released. However, the carbon dioxide molecules don’t actually contain carbon atoms from the acetyl

CoA

that just entered the cycle. Instead, the carbons from acetyl

CoA

are initially incorporated into the intermediates of the cycle and are released as carbon dioxide only during later turns. After enough turns, all the carbon atoms from the acetyl group of acetyl

CoA

will be released as carbon dioxide.

Where’s all the $ATP$ ‍?

You may be thinking that the

ATP

output of the citric acid cycle seems pretty unimpressive. All that work for just one

ATP

GTP

It’s true that the citric acid cycle doesn’t produce much

ATP

directly. However, it can make a lot of

ATP

indirectly, by way of the

NADH

and

{FADH}_{2}

it generates. These electron carriers will connect with the last portion of cellular respiration, depositing their electrons into the electron transport chain to drive synthesis of ATP molecules through oxidative phosphorylation.

Attribution:

This article is adapted from “Oxidation of pyruvate and the citric acid cycle” by OpenStax Biology, CC BY 3.0.

Download the original article for free at http://cnx.org/contents/185cbf87-c72e-48f5-b51e-f14f21b5eabd@9.85:36/Oxidation-of-Pyruvate-and-the-.

The modified article is licensed under a CC BY-NC-SA 4.0 license.

Berg, J. M., J. A. Tymoczko, and L. Stryer. "The Citric Acid Cycle." In Biochemistry. 6th ed. (New York, NY: W.H. Freeman and Company, 2007), 485.
Berg, J. M., J. A. Tymoczko, and L. Stryer. "The Citric Acid Cycle." In Biochemistry. 6th ed. (New York, NY: W.H. Freeman and Company, 2007), 492.
Raven, P. H., G. B. Johnson, K. A. Mason, J. B. Losos, and S. R. Singer. "How Cells Harvest Energy." In Biology. 10th AP ed. (New York, NY: McGraw-Hill, 2014), 132-133.
Pasani, S. "Why Is FADH2 Made Instead of NADH in One of the Reaction of Krebs Cycle? [answer]." Biology Stack Exchange. September 7, 2013. http://biology.stackexchange.com/questions/10313/why-is-fadh2-made-instead-of-nadh-in-one-of-the-reaction-of-krebs-cycle.
Berg, J. M., J. A. Tymoczko, and L. Stryer. "The Citric Acid Cycle." In Biochemistry. 6th ed. (New York, NY: W.H. Freeman and Company, 2007), 487-488.

Additional references

Berg, J. M., J. A. Tymoczko, and L. Stryer. "The Citric Acid Cycle." In Biochemistry, 475-501. 6th ed. New York, NY: W.H. Freeman and Company, 2007.

Caprette, D. R. "Hans Krebs (1900-1981)." Experimental Biosciences: Resources for Introductory & Intermediate Level Lab Courses. May 26, 2005. http://www.ruf.rice.edu/~bioslabs/studies/mitochondria/krebs.html.

"Citric Acid Cycle." Wikipedia. August 23, 2015. Accessed September 10, 2015. https://en.wikipedia.org/wiki/Citric_acid_cycle.

"Hans Adolf Krebs." Wikipedia. August 15, 2015. Accessed September 10, 2015. https://en.wikipedia.org/wiki/Hans_Adolf_Krebs.

Karp, Gerald. "The Role of Mitochondria in the Formation of ATP." In Cell and Molecular Biology: Concepts and Experiments, 182-91. 6th ed. Hoboken, NJ: Wiley, 2010.

Krantz, B. "Citric Acid Cycle." 2008. https://mcb.berkeley.edu/labs/krantz/mcb102/lect_S2008/MCB102-SPRING2008-LECTURE8-CITRIC_ACID_CYCLE.pdf.

Krebs, Hans Adolf, and Leonard Victor Eggleston. "The Oxidation of Pyruvate in Pigeon Breast Muscle." Biochem. J. Biochemical Journal 34, no. 3 (1940): 442-59. doi:10.1042/bj0340442.

Lehninger, A., D. Nelson, and M. Cox. "Regulation of the Citric Acid Cycle." In Principles of Biochemistry. 2nd ed. New York, NY: Worth Publishers, 1992.

Pasani, S. "Why Is FADH2 Made Instead of NADH in One of the Reaction of Krebs Cycle? [answer]." Biology Stack Exchange. September 7, 2013. http://biology.stackexchange.com/questions/10313/why-is-fadh2-made-instead-of-nadh-in-one-of-the-reaction-of-krebs-cycle.

Raven, P. H., G. B. Johnson, K. A. Mason, J. B. Losos, and S. R. Singer. "How Cells Harvest Energy." In Biology, 122-46. 10th AP ed. New York, NY: McGraw-Hill, 2014.

"Redox Reactions." Essential Biochemistry. 2004. http://www.wiley.com/college/pratt/0471393878/student/review/redox/4_reduction_potential.html.

Reece, J. B., L. A. Urry, M. L. Cain, S. A. Wasserman, P. V. Minorsky, and R. B. Jackson. "Cellular Respiration and Fermentation." In Campbell Biology, 162-84. 10th ed. San Francisco, CA: Pearson, 2011.

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PrincessDeen101
Posted 8 years ago. Direct link to PrincessDeen101's post “Is there a difference bet...”
Is there a difference between ATP and GTP?
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(13 votes)
Answer
- William H
  Posted 8 years ago. Direct link to William H's post “ATP is adenosine triphosp...”
  ATP is adenosine triphosphate, or adenine (the DNA base) with a ribose (the sugar) attached which makes it adenosine, then with three phosphate groups added. GTP is all the same stuff, except for Guanine substituted in for Adenine.
  Comment on William H's post “ATP is adenosine triphosp...”
  (61 votes)
VINI
Posted 8 years ago. Direct link to VINI's post “Explain why citric acid c...”
Explain why citric acid cycle can't operate in the absence of oxygen?
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(16 votes)
Answer
- Ali Sasani
  Posted 7 years ago. Direct link to Ali Sasani's post “Cooper is right... Once ...”
  Cooper is right...
  
  Once the ETC stops oxidizing NADH to NAD+ there is no longer any NAD+ available for the Krebs cycle to reduce back to NADH and the cycle comes to a halt. Therefore, the Krebs cycle is actually regulated by the availability of NAD+
  
  It is true that the Fermentation process an contribute to NAD+ regeneration but remember that under anaerobic condition most of the cell's pyruvate is being sent to the Fermentation pathway... and even when NAD+ is regenerated during Fermentation, there will be much less Pyruvate (I'm trying to avoid words like "none") entering the Kreb's Cycle.
  
  All this being said, yes technically it can but it would not be contributing to the overall goal (ETC) so the ATP production will be significantly less.
  Button navigates to signup page
  (23 votes)
Mohammad mahdy yousefi
Posted 8 years ago. Direct link to Mohammad mahdy yousefi's post “How kerebs found this cyc...”
How kerebs found this cycle?
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(5 votes)
Answer
- Darmon
  Posted 8 years ago. Direct link to Darmon's post “Krebs was working on the ...”
  Krebs was working on the problem of finding the chemicals that act as intermediaries in cellular respiration. He discovered that when he added certain chemicals to pigeon breast muscle cells, their oxygen consumption would increase, thus indicating that more respiration reactions were taking place. These chemicals are the same ones we now identify as those making up the Kreb's Cycle. :)
  Comment on Darmon's post “Krebs was working on the ...”
  (20 votes)
Devon Dryer
Posted 8 years ago. Direct link to Devon Dryer's post “Which provides more energ...”
Which provides more energy output, 1 ATP molecule or 1 GTP molecule?
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(7 votes)
Answer
- Chunhku
  Posted 8 years ago. Direct link to Chunhku's post “The difference between AT...”
  The difference between ATP and GTP is not on their energy output, but on their relative abundance in cells. There are far more ATP than GTP in cells to provide energy, because of evolution.
  Comment on Chunhku's post “The difference between AT...”
  (10 votes)
fiky95
Posted 8 years ago. Direct link to fiky95's post “I was wondering whether i...”
I was wondering whether it's necessary to remember the formula of each compound? Thank you! :)
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(3 votes)
Answer
- William H
  Posted 8 years ago. Direct link to William H's post “Most basic biology classe...”
  Most basic biology classes, even AP bio don't require you to know the exact structure, although you might want to know their basic structure such as oh this is glucose with a phosphate group attached, this is a molecule with an extra proton, since most questions in that topic will revolve around that.
  Comment on William H's post “Most basic biology classe...”
  (12 votes)
BSnailer
Posted 8 years ago. Direct link to BSnailer's post “Going from Malate to Oxal...”
Going from Malate to Oxaloacetic Acid 2 hydrogen ions are hydrolyzed but only one NADH is formed. Where did the other Hydrogen Ion go?
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(5 votes)
Answer
- Maxime
  Posted 8 years ago. Direct link to Maxime's post “NAD+ needs 2 electrons en...”
  NAD+ needs 2 electrons en 1 proton to make NADH.
  The oxidation of malate transfers these products to NAD+. There is indeed a remaining H+ ion that is released in the matrix as a proton. That way the charge is kept on both ends of the reaction.
  This also happens with the other times that NADH is formed (releasing a proton) but there the proton was released beforehand when the carboxyl group was created.
  Button navigates to signup page
  (4 votes)
Martin
Posted 5 years ago. Direct link to Martin's post “Can GTP serve the same fu...”
Can GTP serve the same functions as ATP?
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(3 votes)
Answer
- tyersome
  Posted 5 years ago. Direct link to tyersome's post “They are both energy carr...”
  They are both energy carriers and there are even enzymes that will exchange high-energy phosphates among ribonucleotides§.
  
  However, these molecules are not interchangeable at a molecular level — most enzymes can only use one or the other as a source of energy.
  
  For example, ribosomes use GTP (never ATP) to drive the correct decoding of the codons in mRNA — in contrast, aminoacyl-tRNA synthetases can only use ATP to couple amino acids to the correct tRNA‡.
  
  Does that help?
  
  §Note: Nucleoside-diphosphate kinases (NDKs) — for details see:
  https://en.wikipedia.org/wiki/Nucleoside-diphosphate_kinase
  
  ‡Note: Khan academy has more about these processes here:
  https://www.khanacademy.org/science/biology/gene-expression-central-dogma#translation-polypeptides
  Button navigates to signup page
  (5 votes)
Gale
Posted a year ago. Direct link to Gale's post “If using this for CLEP bi...”
If using this for CLEP bio should I memorize this cycle and equation?
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(3 votes)
Answer
- FrozenPhoenix45
  Posted a year ago. Direct link to FrozenPhoenix45's post “Having taken the CLEP Bio...”
  Having taken the CLEP Biology exam, I would recommend it. You may not come across it, but it can't hurt. I had a few questions regarding this, but I can't remember whether I needed the equation memorized. I still memorized it though, because I would rather know it and not need it than not know it and need it.
  Comment on FrozenPhoenix45's post “Having taken the CLEP Bio...”
  (5 votes)
caominh11122000
Posted 8 years ago. Direct link to caominh11122000's post “In the picture "Oxidation...”
In the picture "Oxidation of pyruvate and citric acid cycle", in step 3 and 4, I saw there are 2 H+ ions produced but I'm not sure where they came from. I think there should be no spare H+ ion in step 3 and 4.
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(4 votes)
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- Ivana - Science trainee
  Posted 5 years ago. Direct link to Ivana - Science trainee's post “They are not spare, that'...”
  They are not spare, that's the way NAD+ is reduced. Those H+ ions are used in generating proton gradient later for ETC.
  Button navigates to signup page
  (2 votes)
Thatmysticchick
Posted a year ago. Direct link to Thatmysticchick's post “SOMEBODY PLEASE HELP IT’S...”
SOMEBODY PLEASE HELP IT’S DRIVING ME NUTS!
Synthethases are ligase enzymes and differ from synthases in that they use energy in the reaction derived from a nucleoside triphosphate. I’m aware the nomenclature has changed to using synthases for the same purpose but that’s recent. I REALLY WANT TO UNDERSTAND how the enzyme responsible for the PRODUCTION of GTP/ATP (the only one for that matter) is a SYNTHETASE given that they USE gtp/atp, NOT PRODUCE. Please and Thank you very much in advance!
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