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Mechanisms of Thiamine diphosphateThe mechanisms below have been extracted from MACiE. The substrates and products are abstracted to their essential parts, which are necessary to explain the reaction the cofactor takes part in. The atoms involved in the next step are highlighted in red, and the ones that have been changed by the last step are shown in green. Red takes precedence when both applies.Activation of Thiamine diphosphate
Mechanism #1 for Thiamine diphosphate
Description of mechanismAll ThDP dependant enzymes catalyse reactions with two halves, the first one involving general acid-base reaction, in which the carbanion attacks an organic atom and results in the cleavage of a bond, the attachment of the ThDP in its imino form to the substrate and the release of the first product. The second half reaction involves a nucleophilic attack of the enamine intermediate on second substrate and results in ligation (=product). It is more diverse than the first half and depends on the substrates of the reaction. [1] Catalysis follows ping-pong-mechanism kinetics, which is structurally realised by a dimer with two active sites in opposite states. A proton wire (over 20Å) between the two active sites passes a proton from one site to the other, toggling their states. [1] Experiments revealed the presence of a delocalized pi radical on the enamine-thiazolium intermediate. [2] The mechanism has two alternative routes, one of which constantly produces ROS and only one reaction step involving a radical, whilst the other route comprises three steps with radicals. [2] The structure of phosphoketolase (EC 4.1.2.9) has recently shown that the enzyme contains a ThDP-dependant dehydration step [3]. References
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