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  • When might an organism use the ED pathway or the PPP for glycolysis?

Transition reaction, coenzyme a, and the krebs cycle

Glycolysis produces pyruvate, which can be further oxidized to capture more energy. For pyruvate to enter the next oxidative pathway, it must first be decarboxylated by the enzyme complex pyruvate dehydrogenase to a two-carbon acetyl group in the transition reaction , also called the bridge reaction (see Appendix C and [link] ). In the transition reaction, electrons are also transferred to NAD + to form NADH. To proceed to the next phase of this metabolic process, the comparatively tiny two-carbon acetyl must be attached to a very large carrier compound called coenzyme A (CoA) . The transition reaction occurs in the mitochondrial matrix of eukaryotes; in prokaryotes, it occurs in the cytoplasm because prokaryotes lack membrane-enclosed organelles.

Coenzyme A is made of a 5 carbon sugar in a ring. Attached to carbon 1 is adenine, attached to carbon 3 is a phosphate group. Attached to carbon 5 (which is out of the ring) are two phosphate groups and a carbon/nitrogen chain with a sulfur at the end. The acetyl group binds to this final sulfur.
(a) Coenzyme A is shown here without an attached acetyl group. (b) Coenzyme A is shown here with an attached acetyl group.

The Krebs cycle transfers remaining electrons from the acetyl group produced during the transition reaction to electron carrier molecules, thus reducing them. The Krebs cycle also occurs in the cytoplasm of prokaryotes along with glycolysis and the transition reaction, but it takes place in the mitochondrial matrix of eukaryotic cells where the transition reaction also occurs. The Krebs cycle is named after its discoverer, British scientist Hans Adolf Krebs (1900–1981) and is also called the citric acid cycle , or the tricarboxylic acid cycle (TCA) because citric acid has three carboxyl groups in its structure. Unlike glycolysis, the Krebs cycle is a closed loop: The last part of the pathway regenerates the compound used in the first step ( [link] ). The eight steps of the cycle are a series of chemical reactions that capture the two-carbon acetyl group (the CoA carrier does not enter the Krebs cycle) from the transition reaction, which is added to a four-carbon intermediate in the Krebs cycle, producing the six-carbon intermediate citric acid (giving the alternate name for this cycle). As one turn of the cycle returns to the starting point of the four-carbon intermediate, the cycle produces two CO 2 molecules, one ATP molecule (or an equivalent, such as guanosine triphosphate [GTP]) produced by substrate-level phosphorylation, and three molecules of NADH and one of FADH 2 . (A discussion and detailed illustration of the full Krebs cycle appear in Appendix C .)

Although many organisms use the Krebs cycle as described as part of glucose metabolism, several of the intermediate compounds in the Krebs cycle can be used in synthesizing a wide variety of important cellular molecules, including amino acids, chlorophylls, fatty acids, and nucleotides; therefore, the cycle is both anabolic and catabolic ( [link] ).

The citric acid cycle is drawn as a circle with arrows around the outside showing what enters and exits the cycle. 3 NAD+ are converted to 3 NADH, 1 FAD is converted to 1 FADH2, 2 CO2 leave the cycle, ADP or GDP are converted to ATP or GTP. Acetyl-CoA enters and CoA leaves (leaving the 2 carbons as part of the cycle.
The Krebs cycle, also known as the citric acid cycle, is summarized here. Note incoming two-carbon acetyl results in the main outputs per turn of two CO 2 , three NADH, one FADH 2 , and one ATP (or GTP) molecules made by substrate-level phosphorylation. Two turns of the Krebs cycle are required to process all of the carbon from one glucose molecule.
Details of the Kreb’s cycle. Acetyl-CoA (C2) enter at the top (along with water). SH-CoA leaves. The 2 carbons of Acetyl-CoA bind with the 4 carbons of oxaloacetate for form citrate (C6). An arrow shows that this can be used to build fatty acids and sterols. Citrate is converted to isocitrate (C6). Isocitrate is converted to alpha-ketoglutarate. This step builds 1 NADH/H+ from NADH and releases 1 CO2. Alpha-ketoglutarate can be used to build glutamate which can be used to build other amino acids and nucleotides. Alpha-ketoglutarate is converted to succinyl CoA (C4) by the addition of SH-CoA. This step builds one NADH/H+ from NAH+ and releases a CO2. Succinyl CoA can be used to build porphyrins, heme, and chlorophyll. Succinyl-CoA is converted to Succinate (C4). This step releases SH-CO and builds ATP or GTP from ADP or GDP and Pi. Succinate is converted to fumarate (C4). This step produces FADH2 from FAD. Fumarate is converted to malate (C4) with the addition of water. Malate is converted to oxaloacetate. This step produces NADH/H+ from NAD+. Oxoaloacetate can be used to build asparate which can be used to build nucleotides and other amino acids. Oxaloacetate can also continue in another cycle of the Kreb’s cycle
Many organisms use intermediates from the Krebs cycle, such as amino acids, fatty acids, and nucleotides, as building blocks for biosynthesis.

Key concepts and summary

  • Glycolysis is the first step in the breakdown of glucose, resulting in the formation of ATP, which is produced by substrate-level phosphorylation ; NADH; and two pyruvate molecules. Glycolysis does not use oxygen and is not oxygen dependent.
  • After glycolysis, a three-carbon pyruvate is decarboxylated to form a two-carbon acetyl group, coupled with the formation of NADH. The acetyl group is attached to a large carrier compound called coenzyme A.
  • After the transition step, coenzyme A transports the two-carbon acetyl to the Krebs cycle , where the two carbons enter the cycle. Per turn of the cycle, one acetyl group derived from glycolysis is further oxidized, producing three NADH molecules, one FADH 2 , and one ATP by substrate-level phosphorylation , and releasing two CO 2 molecules.
  • The Krebs cycle may be used for other purposes. Many of the intermediates are used to synthesize important cellular molecules, including amino acids, chlorophylls, fatty acids, and nucleotides.

True/false

Glycolysis requires oxygen or another inorganic final electron acceptor to proceed.

False

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Fill in the blank

Per turn of the Krebs cycle, one acetyl is oxidized, forming ____ CO 2 , ____ ATP, ____ NADH, and ____ FADH 2 molecules.

2; 1; 3; 1

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Most commonly, glycolysis occurs by the ________ pathway.

Embden-Meyerhof

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Short answer

What is substrate-level phosphorylation? When does it occur during the breakdown of glucose to CO 2 ?

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Why is the Krebs cycle important in both catabolism and anabolism?

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Source:  OpenStax, Microbiology. OpenStax CNX. Nov 01, 2016 Download for free at http://cnx.org/content/col12087/1.4
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