Question

acetyl-CoA COA The reactions of the citric acid cycle are shown in the image. As labeled in the diagram, reactions 1, 3, and 4 are regulation points in the citric acid cycle. oxaloacetate citrate synthase citrate NADH +Hi 7 malate dehydrogenase NAD malate aconitase 2 Which molecule inhibits reaction 1? isocitrate 7 fumarase NAD isocitrate dehydrogenase 3 NADH + H+ O citrate O NAD acetyl-CoA + CO2 fumarate C-ketoglutarate FADH succinate O dehydrogenase FAD O-ketoglutarate a dehydrogenase NAD + COA succinate Which molecule inhibits reaction 3? 5 succinyl-CoA synthetase NADH + H + CO2 succinyl-CoA GTP + COA O isocitrate GDP +P O ADP NADH Select every molecule or ion that activates reaction 3. NADPH ADP Ca2+

Answer 1

Citric acid cycle or Kreb's cycle is one of the fundamental steps of chemical reactions of aerobic/cellular respiration. It takes place in mitochondria. It generates high energy molecules and provides many intermediate products which are the substrate for other metabolic pathways. Therefore tight regulation of cycle is a very important phenomenon otherwise continuous generation of high energy molecules and byproducts are not good for cells.

• Acetyl CoA inhibits reaction 1. The first reaction of the citric acid cycle involves condensation of two carbon Acetyl CoA with a four-carbon compound oxaloacetic acid to generate citrate (six-carbon molecule). This reaction is catalyzed by citrate synthase. A higher concentration of acetyl CoA which is a substrate of the reaction indicates that enough amount of energy is available for the cell and inhibits the reaction to proceed further. Citrate can also inhibit the reaction (product inhibition).
• NADH inhibits reaction 3. The third reaction of the cycle is catalyzed by isocitrate dehydrogenase. It is an important enzyme as it regulates the oxidative decarboxylation of isocitrate (six-carbon) into alpha-ketoglutarate (five-carbon). NADH is generated in the third reaction and a higher level of NADH inhibits enzyme activity by displacing NAD+ that results in inhibition of the reaction.
• Ca+ and ADP activate reaction 3. Calcium plays an important role in the regulation of the citric acid cycle. An increase in Ca+ and ADP concentration in mitochondria stimulates the enzyme activity by decreasing the Km of substrate for isocitrate dehydrogenase enzyme. ADP or ATP is required for this calcium sensitivity.  
• NADH inhibits reaction 4. Alpha-ketoglutarate dehydrogenase is another enzyme that catalyzes the regulatory step of cycle. It catalyzes the oxidative decarboxylation of alpha-ketoglutarate to succinyl CoA. The enzyme is inhabited by the products of reaction NADH and succinyl CoA. NADH supply electron to the electron transport chain that generate energy in the form of ATP via oxidative phosphorylation. An increase in cell charge (high ATP) inhibits the citric acid cycle.
• Ca+ activates reaction 4. Calcium ion activates the reaction by decreasing the Km of substrate for alpha-ketoglutarate dehydrogenase enzyme.