So, we kind of skipped the pyruvate dehydrogenase complex and its important. We talked about how we end up with pyruvate at the end of glycolysis, right? It’s our final product. We also talked about how it gets converted to Acetyl-CoA to be used for the Citric Acid cycle. Pyruvate Dehydrogenase Complex is how that happens.

This process is at work in the mitochondrial complex and is active in our fed state. So, to make this happen, we take pyruvate, NAD+ and CoA. What comes out are acetyl-CoA, CO2 and NADH.

The first stage is catalyzed by an enzyme called pyruvate dehydrogenase, also called E1. Obviously, we’re going to need a pyruvate but we also need the cofactor vitamin B1 (thiamine pyrophosphate, aka TPP). This is the rate limiting step of this complex.

Second stage uses dihydrolipoy transacetylase (E2) to transfer an acetyl group to coenzyme A to make our acetyl-CoA. That of course can go into our citric acid cycle.

Last, is dihydrolipoy dehydrogenase (E3) which is going to produce an FADH2. That FADH2 meets up with an NAD who oxidizes it and produces NADH.

That’s about the gist of it. Obviously it’s more complicated than that, but since our focus is on medical school we really don’t need to go much further than this on the pyruvate dehydrogenase complex. It is good to know what happens when it goes wrong, though. When we don’t do this process, pyruvate starts to buildup. That kicks in lactate dehydrogenase which is going to start creating lactate. So, we get things like lactic acidosis, but also neurologic defects and increased levels of alanine in the blood. This is an X-linked genetic disorder.

Come back again next week and we’ll look at some more metabolic pathways!