Citrate Synthesis and Isomerization in TCA

The irreversible condensation of acetyl CoA and oxaloacetate (OAA) to form citrate (a tricarboxylic acid) is catalyzed by citrate synthase, the initiating enzyme of the TCA cycle (Fig. 1). This aldol condensation has a highly negative change in standard free energy ([ΔG0] ), which strongly favors citrate formation. The enzyme is inhibited by citrate (product inhibition).
Substrate availability is another means of regulation for citrate synthase. The binding of OAA greatly increases the enzyme’s affinity for acetyl CoA. [Note: Citrate, in addition to being an intermediate in the TCA cycle, is a source of acetyl CoA for the cytosolic synthesis of fatty acids and cholesterol . Citrate also inhibits phosphofructokinase-1 (PFK-1), the rate-limiting enzyme of glycolysis , and activates acetyl CoA carboxylase (the rate-limiting enzyme of fatty acid synthesis.]

Figure 1: Formation of α-ketoglutarate from acetyl coenzyme A (CoA) and oxaloacetate. NAD(H) = nicotinamide adenine dinucleotide; CO2 = carbon dioxide.
Citrate isomerization
Citrate is isomerized to isocitrate through hydroxyl group migration catalyzed by aconitase (aconitate hydratase), an iron-sulfur protein (see Fig. 1). [Note: Aconitase is inhibited by fluoroacetate, a plant toxin that is used as a pesticide. Fluoroacetate is converted to fluoroacetyl CoA that condenses with OAA to form fluorocitrate, a potent inhibitor of aconitase.]

مواضيع ذات صلة

Blood clotting (coagulation)

Platelet Plug Formation: Aggregation

Platelet Plug Formation: Activation

Platelet Plug Formation: Adhesion

Limiting Clotting : Fibrinolysis

Limiting Clotting : Inactivating proteins

Fibrin Meshwork Formation : Pathways

Fibrin Meshwork Formation : Formation of γ-carboxyglutamate residues

Fibrin Meshwork Formation :Role of phosphatidylserine and calcium

Fibrin Meshwork Formation: Proteolytic cascade

Blood Clotting : Overview

Biotechnology and Human Disease