acetylation

Examples of acetylation in the following topics:

• 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

• 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.
  • 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. .
  • The ability to utilize the acetyl-CoA pathway is advantageous due to the ability to utilize both hydrogen and carbon dioxide to produce acetyl-CoA.
  • Describe the role of the carbon monoxide dehydrogenase and acetyl-CoA synthetase in the acetyl-CoA pathway

• 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.

• Connecting Lipids to Glucose Metabolism

  • 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.
  • 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.

• Acetyl CoA and the Citric Acid Cycle

  • The cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD+ to NADH, and produces carbon dioxide.
  • Through the catabolism of sugars, fats, and proteins, a two carbon organic product acetate in the form of acetyl-CoA is produced.
  • 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.

• 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.
  • 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.
  • Through a series of steps, citrate is oxidized, releasing two carbon dioxide molecules for each acetyl group fed into the cycle.

• Reactions of Substituent Groups

  • By acetylating the heteroatom substituent on phenol and aniline, its activating influence can be substantially attenuated.
  • The modifying acetyl group can then be removed by acid-catalyzed hydrolysis (last step), to yield para-nitroaniline.
  • Although the activating influence of the amino group has been reduced by this procedure, the acetyl derivative remains an ortho/para-directing and activating substituent.
  • The following diagram illustrates how the acetyl group acts to attenuate the overall electron donating character of oxygen and nitrogen.
  • Acetyl group attenuates the electron donating character of oxygen and nitrogen

• Biosynthesis and Energy

  • The major pathways utilized to ensure fixation of carbon dioxide include: the Calvin cycle, the reductive TCA cycle, and the acetyl-CoA pathway.
  • In the acetyl-CoA pathway, carbon dioxide is reduced to carbon monoxide and then acetyl-CoA.

• Epigenetic Alterations in Cancer

  • Histone proteins that surround that region lack the acetylation modification (the addition of an acetyl group) that is present when the genes are expressed in normal cells.
  • Because these changes are temporary and can be reversed (for example, by preventing the action of the histone deacetylase protein that removes acetyl groups, or by DNA methyl transferase enzymes that add methyl groups to cytosines in DNA) it is possible to design new drugs and new therapies to take advantage of the reversible nature of these processes.