Aerobic Glucose Metabolism

Krebs cycle chemistry

The overall goal in the Krebs cycle is to add the two carbon acetyl group ON to a four carbon compound called oxaloacetate ... then remove two carbons (one at a time as CO₂) and then end back up at oxaloacetate again. Since the pathway both starts and ends with the same compound it is termed a cycle.

The trick here is that the carbons taken off as carbon dioxide are NOT the same ones put on as the original acetyl group in the first place. As you look at these reactions, label the "original" acetyl group and follow them as you go around the cycle.

I want highlight a couple of the enzymes in the cycle. Their overall chemistry appears to be quite complex. Yet, when broken down into pieces still use just the five main chemistries that have been used all along. For instance, citrate synthase forms a C-C bond between the oxaloacetate and the acetyl group (of acetyl-CoA). To do this must require an aldol reaction. But it must also perform a hydrolysis to cleave off the Coenzyme-A to yield citrate. These two consecutive reactions occur on the same enzyme, at the same active site. Other enzymes that perform multiple chemistries are:

• citrate synthase
  1. aldol reaction
  2. hydrolysis
• aconitase
  1. dehydration (elimination)
  2. hydration (reverse of the obove reaction but in a different location)
• isocitrate dehydrogenase
  1. oxidation
  2. aldol cleavage (removal of the second CO₂)
• a-ketoglutarate dehydrogenase in a reaction VERY SIMILAR to pyruvate dehydrogenase
  1. aldol cleavage (removal of the third and last CO₂)
  2. oxidation
  3. group transfer