Topic 18: TCA Flashcards
Name the 3 enzymes and five coenzymes of the pyruvate dehyrogenase complex
The pyruvate dehydrogenase complex requires the participation of the three enzymes of the pyruvate dehydrogenase complex, pyruvate dehydrogenase, dihydrolipoyl transacetylase, and dihydrolipoyl dehydrogenase, as well as five coenzymes. The coenzymes, thiamine pyrophosphate (TPP), lipoic acid and flavin adenine dinucleotide (FAD) serve as catalytic coenzymes and CoA and nicotinamide adenine dinucleotide (NAD+) are stoichiometric enzymes
Fully detail the process of pyruvate to acetyl coA
The conversion of acetyl CoA from pyruvate consists of three steps, decarboxylation, oxidation and the transfer of the resultant acetyl group (H3C-C(-R)=O). These steps must be coupled to preserve the free energy derived from the decarboxylation step to drive the formation of NADH and acetyl CoA
Decarboxylation: Pyruvate combines with the ionized (carbanion) form of TPP and is then decarboxylated to yield hydroxyethyl-TPP. This reaction. The limiting step in the synthesis of acetyl coA, is catalyzed by the pyruvate dehydrogenase component (E1) of the multienzyme complex. TPP is the coenzyme of the pyruvate dehydrogenase component
Oxidation: The hydroxyethyl group attached to TPP is oxidized to form an acetyl group while being simultaneously transferred to lipoamide, a derivative of lipoic acid. Note that this transfer results in the formation of an energy rich thioester bond
The disulfide group of lipoamide is reduced to its sulfhydryl form in this reaction. The reaction, also catalyzed by pyruvate dehydrogenase, E1, yields acetyl-lipoamide
Formation of acetyl CoA: The acetyl group is then transferred from acetyl-lipoamide to CoA to form acetyl CoA. Dihydrolipoyl transferase (E2) catalyzes this reaction. The energy-rich thioester bond is preserved as the acetyl group is transferred to CoA. Acetyl CoA, fuel for the citric acid cycle, has now been generated from pyruvate.
However, the pyruvate dehydrogenase complex cannot complete another catalytic cycle until the dihydrolipoamide is oxidized to lipoamide. So in a fourth step, the oxidized form of lipoamide is regenerated by dihydrolipoyl dehydrogenase (E3). Two electrons are transferred to an FAD prosthetic group of the enzyme and then to NAD+.
This electron transfer from FAD to NAD+ is unusual because as we will see, the common roel for FAD is to receive electrons from NADH. The electron-trasnfer potential of FAD is increased by its association with the enzyme, enabling it to transfer electrons to NAD+. Proteins tightly associated with FAD are called flavoproteins
