acetyl CoA

Examples of acetyl CoA in the following topics:

• The Acetyl-CoA Pathway

  • The acetyl-CoA pathway utilizes carbon dioxide as a carbon source and often times, hydrogen as an electron donor to produce acetyl-CoA.
  • The following is a brief overview of the acetyl-CoA pathway. .
  • Acetyl-CoA synthetase is a class of enzymes that is key to the acetyl-CoA pathway.
  • The acetyl-CoA synthetase functions in combining the carbon monoxide and a methyl group to produce acetyl-CoA. .
  • Describe the role of the carbon monoxide dehydrogenase and acetyl-CoA synthetase in the acetyl-CoA pathway

• Acetyl CoA to CO2

  • The acetyl carbons of acetyl CoA are released as carbon dioxide in the citric acid cycle.
  • Acetyl CoA links glycolysis and pyruvate oxidation with the citric acid cycle.
  • In the presence of oxygen, acetyl CoA delivers its acetyl group to a four-carbon molecule, oxaloacetate, to form citrate, a six-carbon molecule with three carboxyl groups.
  • For each molecule of acetyl CoA that enters the citric acid cycle, two carbon dioxide molecules are released, removing the carbons from the acetyl group.
  • Describe the fate of the acetyl CoA carbons in the citric acid cycle

• Breakdown of Pyruvate

  • After glycolysis, pyruvate is converted into acetyl CoA in order to enter the citric acid cycle.
  • In order for pyruvate, the product of glycolysis, to enter the next pathway, it must undergo several changes to become acetyl Coenzyme A (acetyl CoA).
  • The conversion of pyruvate to acetyl CoA is a three-step process .
  • The enzyme-bound acetyl group is transferred to CoA, producing a molecule of acetyl CoA.
  • The remaining two carbons are then transferred to the enzyme CoA to produce Acetyl CoA.

• The 3-Hydroxypropionate Cycle

  • The 3-hydroxypropionate cycle is a carbon fixation pathway that results in the production of acetyl-CoA and glyoxylate.
  • Specifically, in this cycle, the carbon dioxide is fixed by acetyl-CoA and propionyl-CoA carboxylases.
  • This process results in the formation of malyl-CoA which is further split into acetyl-CoA and glyoxylate.
  • The acetyl-CoA carboxylase utilized in this cycle is biotin-dependent as well and catalyzes the carboxylation of acetyl-CoA to malonyl-CoA.
  • This pathway produces pyruvate via conversion of bicarbonate and also results in the production of intermediates such as acetyl-CoA, gloxylate and succinyl-CoA.

• Acetyl CoA and the Citric Acid Cycle

  • Through the catabolism of sugars, fats, and proteins, a two carbon organic product acetate in the form of acetyl-CoA is produced.
  • Acetyl-CoA along with two equivalents of water (H2O) are consumed by the citric acid cycle, producing two equivalents of carbon dioxide (CO2) and one equivalent of HS-CoA.
  • This generates acetyl-CoA according to the following reaction scheme:
  • CH3C(=O)C(=O)O– (pyruvate) + HSCoA + NAD+ → CH3C(=O)SCoA (acetyl-CoA) + NADH + H+ + CO2
  • The product of this reaction, acetyl-CoA, is the starting point for the citric acid cycle.

• Organic Acid Metabolism

  • This process requires the β-oxidation pathway, a cyclic process that catalyzes the sequential shortening of fatty acid acyl chains to the final product, acetyl-CoA.
  • Fatty acid chains are converted to enoyl-CoA (catalyzed by acyl-CoA dehydrogenase).
  • 3-ketoacyl-CoA is thiolated (by 3-ketoacyl-CoA thiolase) to yield one molecule of acetyl-CoA and a derivative of the original input fatty acid that is now shorter by two carbons.
  • Acertyl-CoA is the entry molecule for the TCA cycle.
  • Free fatty acids are broken down to acetyl-CoA by dedicated enzymes in the β-oxidation pathway.

• Connecting Lipids to Glucose Metabolism

  • Cholesterol contributes to cell membrane flexibility and is a precursor to steroid hormones.
  • The synthesis of cholesterol starts with acetyl groups, which are transferred from acetyl CoA, and proceeds in only one direction; the process cannot be reversed.
  • Triglycerides, a form of long-term energy storage in animals, are made of glycerol and three fatty acids.
  • Fatty acids are catabolized in a process called beta-oxidation that takes place in the matrix of the mitochondria and converts their fatty acid chains into two carbon units of acetyl groups, while producing NADH and FADH2.
  • The acetyl groups are picked up by CoA to form acetyl CoA that proceeds into the citric acid cycle as it combines with oxaloacetate.

• The Reverse TCA Cycle

  • Reverse TCA, a form of carbon fixation, utilizes numerous ATP molecules, hydrogen and carbon dioxide to generate an acetyl CoA.
  • ATP citrate lyase is the enzyme responsible for cleaving citrate into oxaloacetate and acetyl CoA.
  • 4) succinate is converted to succinyl-CoA (ATP is hydrolyzed to ADP+Pi)
  • 5) succincyl CoA is converted to alpha-ketoglutarate via an alpha-ketoglutarate synthase (reduction of carbon dioxide occurs and oxidation of coenzyme A)
  • 8) ATP citrate lyase is then used to convert citrate to oxaloacetate and acetyl CoA (ATP is hydrolyzed to ADP and Pi).

• Lipid Metabolism

  • These fatty acids can then enter a dedicated pathway that promotes step-wise lipid processing that ultimately yields acetyl-CoA, a critical metabolite that conveys carbon atoms to the TCA cycle (aka Krebs cycle or citric acid cycle) to be oxidized for energy production.
  • The acetyl-CoA molecule liberated by this process is eventually converted into ATP through the TCA cycle.
  • Oxidation: The initial step of β-oxidation is catalyzed by acyl-CoA dehydrogenase, which oxidizes the fatty acyl-CoA molecule to yield enoyl-CoA.
  • Cleavage: A thiolase then cleaves off acetyl-CoA from the oxidized molecule, which also yields an acyl-CoA that is two carbons shorter than the original molecule that entered the β-oxidation pathway.
  • This cycle repeats until the fatty acid has been completely reduced to acetyl-CoA, which is fed through the TCA cycle to ultimately yield cellular energy in the form of ATP .

• Citric Acid Cycle

  • Like the conversion of pyruvate to acetyl CoA, the citric acid cycle takes place in the matrix of the mitochondria.
  • The first step is a condensation step, combining the two-carbon acetyl group (from acetyl CoA) with a four-carbon oxaloacetate molecule to form a six-carbon molecule of citrate.
  • CoA is bound to a sulfhydryl group (-SH) and diffuses away to eventually combine with another acetyl group.
  • CoA binds the succinyl group to form succinyl CoA.
  • In the citric acid cycle, the acetyl group from acetyl CoA is attached to a four-carbon oxaloacetate molecule to form a six-carbon citrate molecule.