2. In order to understand the mechanism of cyclooxygenase, the two derivatives of arachidonic acid shown below (A and B) have been prepared. These derivatives are selectively deuterated (i.e. the H atoms at these doubly allylic positions have been replaced with deuterium atoms. This is a very common strategy to elucidate reaction mechanisms. Please predict where the deuterium atoms would end up in the product of the cyclization reaction catalyzed by the enzyme. Assume that the reaction is initiated by a tyrosyl radical by the enzyme, as usual. A OH O= B OH

Understanding the Mechanism of the -Ketoglutarate Dehydrogenase Reaction tshe first step of the -Ketoglutarate dehydrogenase reaction involves decarboxylation of the substrate and leaves a covalent TPP intermediate. Write a reasonable mechanism for this reaction.

Distinguishing the Mechanisms of Class I and Class I Aldolases Fructose bisphosphate aldolase in animal muscle is a class 1 aldolase, which forms a Schiff base intermediate between substrate (for example. fructose-1, 6-bisphosphate or dihydroxyacetone phosphate) and a lysine at the active site (see Figure I8.12). The chemical evidence for this intermediate conies from studies with aldolase and the reducing agent sodium borohydride, NaBH4. Incubation of the enzyme with dihydroxyacetone phosphate and NaBH4 inactivates the enzyme. Interestingly, no inactivation is observed if NabH4 is added to the enzyme in the absence of substrate. Write a mechanism that explains these observations and provides evidence for the formation of a Schiff base intermediate in the aldolase reaction.

Using the ActiveModel for aldose reductase, describe the structure of the TIM barrel motif and the structure and location of the active site.