In addition to NAD:NADH ratio, what is another factor that inhibits alpha-ketoglutarate dehydrogenase activity?

Alpha-ketoglutarate dehydrogenase plays a critical role in the citric acid cycle by catalyzing the conversion of alpha-ketoglutarate to succinyl-CoA, a reaction that is vital for the continuation of the cycle. The activity of this enzyme can be influenced by several factors, one of which is product accumulation.

As alpha-ketoglutarate dehydrogenase catalyzes its reaction, it produces succinyl-CoA and NADH. If there is an accumulation of succinyl-CoA, it can signal that the cycle is effectively running and that there is sufficient supply of downstream metabolites. Higher levels of succinyl-CoA then act as a feedback inhibitor to prevent further conversion of alpha-ketoglutarate, thus inhibiting the activity of alpha-ketoglutarate dehydrogenase. This regulatory mechanism helps maintain metabolic balance within the cell, preventing overproduction of intermediates.

The other factors mentioned, such as acetyl-CoA levels, calcium concentration, and high energy charge, can affect enzyme activity but do not serve as direct inhibitors specifically related to the accumulation of reaction products in the same manner as succinyl-CoA does. In the context of metabolic pathways