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Chapter 12: Cellular Respiration

12.3. Citric Acid Cycle and the Preparatory (or Intermediate) Step

Learning Objectives

By the end of this section, you will be able to:

  • Explain how a circular pathway, such as the citric acid cycle, fundamentally differs from a linear biochemical pathway, such as glycolysis.
  • Describe how pyruvate, the product of glycolysis, is prepared for entry into the citric acid cycle.

Preparatory or intermediate step: pyruvate oxidation

If oxygen is available, the 3-Carbon pyruvates are transported into the mitochondrial matrix where in each molecule a C atom is removed, resulting in CO2 and 2-Carbon acetyl. Acetyl contains a carbonyl and a methyl functional group and is denoted as R−C(=O)−CH3 .

The acetyl is picked up and activated by a carrier called coenzyme A (CoA), forming a compound called acetyl CoA. CoA requires dietary intake of vitamin B5 (pantothenic acid) for its synthesis. Acetyl CoA’s major function in cellular respiration is to deliver the two-Carbon acetyl group to the citric acid cycle (Figure 12.3.1.).

 

This illustration shows the conversion of pyruvate into acetyl upper case C lower case o upper case A. The Pyruvate begins outside the mitochondrion, in the cytosol. When the pyruvate enters the mitochondrion through the pyruvate carrier protein, a carboxyl group is removed from pyruvate, releasing carbon dioxide. Then, a redox reaction forms acetate and N A D H. In step three, the acetate is transferred coenzyme A, forming acetyl upper C lower o upper A.
Figure 12.3.1: Upon entering the mitochondrial matrix, a multienzyme complex converts pyruvate into acetyl CoA. In the process, carbon dioxide is released, and one molecule of NADH is formed. Credit: Rao, A., Ryan, K. and Tag, A. Department of Biology, Texas A&M University.

The end-products are pyruvate oxidation are:

  • 2-Carbon Acetyl CoA
  • CO2 , the first waste product formed in cellular respiration
  • NADH, the high energy electron and H+ carrier derived from reduction of  NAD+

Since there are two pyruvate molecules formed from each glucose molecule, this step occurs twice.

Citric acid cycle

The citric acid cycle is also called the Krebs cycle (after its discoverer) and the tricarboxylic acid cycle (TCA), named for the first molecule in the cycle.

The Krebs cycle takes place in the mitochondrion matrix in the presence of Oxygen. Acetyl CoA delivers its acetyl group to a 4-Carbon molecule, oxaloacetate, the last molecule of the cycle. The 2-Carbon acetyl plus the 4-Carbon oxalacetate form 6-carbon citric acid (TCA), the first molecule of the cycle.

There are eight steps of the citric acid cycle involving a series of redox, dehydration, hydration, and decarboxylation reactions (Figure 12.3.2.).

The end-products of the Krebs cycle are:

  • waste product, CO2, (from each 2-Carbon acetyl groups)
  • ATP (after conversion from another nucleotide guanosine-5′-triphosphate,GTP)
  • NADH, reduction product of coenzyme NAD+
  • FADH2, reduction product of a second coenzyme FADH (also derived from vitamin B)

Note that the Krebs cycle is considered an aerobic pathway. Although the reactions do not directly use O2, its two reduced coenzymes, NADH and FADH2, will transfer their electrons and H+ to Phase 3 (Oxidative Phosphorylation) which does directly use O2.

 

This illustration shows the eight steps of the citric acid cycle. In the first step, the acetyl group from acetyl uppercase C lower case o upper case A is transferred to a four-carbon oxaloacetate molecule to form a six-carbon citrate molecule. In the second step, citrate is rearranged to form isocitrate. In the third step, isocitrate is oxidized to alpha-ketoglutarate. In the process, one N A D H is formed from N A D superscript plus sign baseline; and one carbon dioxide is released. In the fourth step, alpha-ketoglutarate is oxidized and upper C lower o upper A is added, forming succinyl upper C lower o upper A. In the process, another N A D H is formed and another carbon dioxide is released. In the fifth step, upper C lower o upper A is released from succinyl upper C lower o upper A, forming succinate. In the process, one G T P is formed, which is later converted into A T P. In the sixth step, succinate is oxidized to fumarate, and one F A D is reduced to F A D H subscript 2 baseline. In the seventh step, fumarate is converted into malate. In the eighth step, malate is oxidized to oxaloacetate, and another N A D H is formed.
Figure 12.3.2: In the citric acid cycle, the acetyl group from acetyl CoA is attached to a four-carbon oxaloacetate to form a six-carbon citric acid. Citrate is oxidized, releasing two CO2 for each acetyl group fed into the cycle. Three NAD+ and one FADH+ are reduced, and one ATP is produced. Because the final product of the citric acid cycle is also the first reactant, the cycle runs continuously in the presence of sufficient reactants. (Credit: modification of work by “Yikrazuul”/Wikimedia Commons)
Phase 3 will harvest the remainder of the extractable energy from what began as a glucose molecule.

License and attributions:

  • Biology, Second edition, 2018, Clark, M.A. et al. License: CC BY 4.0. Located at https://openstax.org/books/biology-2e/pages/7-3-oxidation-of-pyruvate-and-the-citric-acid-cycle

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BIO130: Introduction to Physiology Copyright © 2024 by Dinor Dhanabala; Sandra Fraley; and Gordon Lake is licensed under a Creative Commons Attribution 4.0 International License, except where otherwise noted.

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