Energy Balance in the Citric Acid Cycle

How is the Citric Acid Cycle regulated? How does energy remain balanced in the Citric Acid Cycle?

The Krebs cycle is regulated mostly by its own products. Allosteric regulation, or the regulation of an enzyme by binding a molecule to it somewhere other than the active site, is often used to activate and inhibit the Krebs cycle enzymes. ATP, NADH, and acetyl-CoA are all able to allosterically regulate enzymes in the cycle.

How do NADH and ATP regulate the Citric Acid Cycle?

When the cycle reduces NAD+ to NADH, the NADH products can inactivate enzymes that are used early in the cycle. NADH can inactivate pyruvate dehydrogenase, citrate synthase, isocitrate dehydrogenase, and alpha ketoglutarate dehydrogenase. NADH can also inactivate malate, which prevents the overproduction of oxaloacetate.

ATP can inhibit pyruvate dehydrogenase, while ADP can activate it. In cells that use GDP/GTP instead of ATP, the same process can occur.

How do the carbon products of the Citric Acid Cycle self-regulate?

The carbon products of the enzymes in the cycle can also be used to prevent further synthesis. Acetyl-CoA can inhibit pyruvate dehydrogenase. Citrate can inhibit citrate synthase, and succinyl-CoA can inhibit alpha ketoglutarate dehydrogenase. Citrate can also regulate glycolysis by inhibiting phosphofructokinase-1.

How does calcium regulate the Citric Acid Cycle?

Calcium ions can be used to activate the cycle because mitochondrial calcium levels are linked to physical activity. High levels of ADP can also activate the cycle for the same reason.

This system of self regulation keeps the cell from wasting materials like pyruvate in the Krebs cycle when energy is already abundant. It also ensures that enough NAD+ is available for glycolysis and other reactions.

In summary, ATP, NADH, and the carbon products like acetyl-CoA and citrate can be used to inhibit the Krebs cycle. ADP, NAD+, and calcium ions can be used to activate the Krebs cycle.

Energy Balance in the Citric Acid Cycle

ATP concentration is primarily responsible for energy balance in the citric acid cycle. When energy supply is low, the citric acid cycle is used to yield ATP, as can be seen in the below balance sheet. On the other hand, when energy supply is high, the inputs for the citric acid cycle are used elsewhere.

"The citric acid cycle is regulated at multiple points. However, in general it is safe to say that it is inhibited by ATP and NADH. The inhibition by NADH keeps it tightly regulated by oxygen supply, since NADH is converted to NAD+ by oxidative phosphorylation. The inhibition by ATP keeps the citric acid cycle in balance with energy supply. When ATP (energy supply) is high, the citric acid cycle is inhibited and precursors to the citric acid cycle (pyruvate, acetyl CoA and amino acids) are diverted into other pathways."

reference: https://www.med.unc.edu/neurology/files/documents/child-teaching-pdf/CITRIC ACID CYCLE.pdf