Regulation of Krebs cycle

The regulatory points (enzymes) of the Krebs cycle are:

 * 1) Citrate synthase
 * 2) Isocitrate dehydrogenase
 * 3) α-ketoglutarate dehydrogenase



The regulatory factors of the Krebs cycle are:

 * 1) NADH / NAD+ ratio – respiratory control
 * 2) ATP / (ADP a AMP) ratio – energy control
 * 3) Krebs cycle substrate availability - substrate control

NADH / NAD+ ratio – respiratory control
The continuation of the Krebs cycle is the respiratory chain, where reduced cofactors are reoxidized. If NADH + H + and FADH2 accumulate (NADH / NAD + ratio increases ), α-ketoglutarate dehydrogenase and isocitrate dehydrogenase are inhibited.

ATP / (ADP a AMP) ratio – energy control
If there is enough energy, α-ketoglutarate dehydrogenase and isocitrate dehydrogenase are inhibited.


 * ATP is their inhibitor.
 * ADP and AMP, on the other hand, are activators.



Krebs cycle substrate availability - substrate control
Substrate control is found at the level of citrate synthase, which produces as much citrate as we supply it with oxaloacetate and acetyl-CoA.

Krebs cycle activity is also related to O2 availability. Even though none of the reactions in the cycle require O2, oxygen is needed for the respiratory chain because it serves as the final electron acceptor. In the respiratory chain, the following are reoxidized:


 * NADH → NAD+
 * FADH2 → FAD

If the cell lacks O2, the concentration of NAD+ and FAD decreases, and subsequently the activity of the Krebs cycle also decreases.