page_title: 1-aminocyclopropane-1-carboxylate synthase
section_title: Enzyme mechanism
hierarchical_section_title: 1-aminocyclopropane-1-carboxylate synthase / Enzyme mechanism
caption_attribution_description: English: chembio draw rendering of Steph 1 of ACS mechanism
context_page_description: Aminocyclopropane-1-carboxylic acid synthase is an enzyme that catalyzes the synthesis of 1-Aminocyclopropane-1-carboxylic acid, a precursor for ethylene, from S-Adenosyl methionine, an intermediate in the Yang cycle and activated methyl cycle and a useful molecule for methyl transfer. ACC synthase, like other PLP dependent enzymes, catalyzes the reaction through a quinonoid zwitterion intermediate and uses cofactor pyridoxal phosphate for stabilization.
  In enzymology, a 1-aminocyclopropane-1-carboxylate synthase is an enzyme that catalyzes the chemical reaction
  S-adenosyl-L-methionine 1-aminocyclopropane-1-carboxylate + methylthioadenosine
  Hence, this enzyme has one substrate, S-adenosyl-L-methionine, and two products, 1-aminocyclopropane-1-carboxylate and methylthioadenosine.
  This enzyme belongs to the family of lyases, specifically carbon-sulfur lyases. The systematic name of this enzyme class is S-adenosyl-L-methionine methylthioadenosine-lyase.
context_section_description: The reaction catalyzed by 1-aminocyclopropane-1-carboxylic acid synthase (ACS) is the committed and rate-limiting step in the biosynthesis of ethylene [20], a gaseous plant hormone that is responsible for the initiation of fruit ripening, shoot and root growth and differentiation, leaf and fruit abscission, flower opening, and flower and leaf senescence. (source) It is a pyridoxal phosphate (PLP) dependent gamma-elimination (?). In the gamma elimination, PLP acts as a sink twice (absorbing electrons from two deprotonations).
  Proposed steps of the reaction mechanism:
  Formation of the ACS-PLP Schiff Base
  Imine Exchange
  Formation of the Quinonoid Intermediate
  Tyrosine and PLP stabilized 3C-Ring formation
  Formation of the ACS-PLP Schiff Base
  The aldehyde of coenzyme PLP reacts to form an imine (Schiff base) linkage with the catalytic domain lysine (278) residue of ACS.
  Imine exchange
  An imine exchange occurs, and the amine nitrogen of the substrate, S-Adenosyl methionine, replaces Lys (278) in the imine linkage. (Stabilized by H bonding).
  Formation of the Quinonoid Intermediate
  PLP acts as an 'electron sink' absorbing delocalized electron density during the reaction intermediates (countering the excess electron density on the deprotonated a-carbon). PLP facilitates the enzyme activity, increasing the acidity of the alpha carbon by stabilizing the conjugate base. The PLP-stabilized carbanion intermediate formed is the quinonoid intermediate.
  Tyrosine and PLP stabilized 3C-Ring formation
  PLP and Tyrosine stabilize negative charges during deprotonation. Tyrosine attacks the sulfur bound carbon, allowing S(CH₃)(Ado) to leave, and during ring formation, Tyrosine leaves.
  Note inhibitors AVG and AMA bind PLP to form a ketimine and oxime respectively (whose reverse reactions are much less favorable) and prevent the ACC synthase catalyzed reaction with SAM.
caption: Formation of the ACS-PLP Schiff Base.
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