Pyruvate oxidation and the TCA Cycle Flashcards
How do we remember the different parts of the TCA cycle?
Officer, Can I Keep Selling Cash For Money?
Oxaloacetate with Acetyl CoA Citrate Isocitrate alpha-ketoglutarate Succinyl CoA Succinate Fumarate Malate
Let’s break down the enzymes and side products for the TCA Cycle.
Officer to Can
Acetyl CoA and Oxaloacetate condense to make Citrate, so we use Citrate Synthase.
Citrate production inhibits this enzyme, so this part of the cycle works best when the cycle is really churning out.
Let’s break down the enzymes and side products for the TCA Cycle.
Can to I
Citrate to isocitrate, so we’re not really doing anything but rearranging. We use the enzyme Aconitase to accomplish this
Wait, why did we rearrange Citrate to Isocitrate? What happens next?
We did this because isocitrate is very special. It’s the first one that can get us some NADH.
Isocitrate is oxidized by isocitrate dehydrogenase to turn NAD+ to NADH and to generate alpha ketoglutarate.
As you might expect due to the pattern previously noted, NADH inhibits this, and ADP (indicating no ATP) stimulates it.
So now we’ve made our first NADH and we have this big ol alpha ketoglutarate. What happens next?
Well now we’ve got the hang of it, so we’re going to want to make another NADH, which means an oxidizing reaction, which means a dehydrogenase enzyme.
We convert alpha ketoglutarate (Keep Selling) to Succinyl CoA using alpha ketoglutarate dehydrogenase. Also, as noted, NAD+ to NADH.
What makes the reaction of alpha-ketoglutarate to succinyl CoA a little more complicated than the first NADH producing reaction?
Well it’s hard to do these things back to back. This second complex needs a lot of cofactors to make it work:
- Thiamine pyrophosphate
- Lipoic Acid
- CoASH
- FAD
- NAD+
Alright so we just had this complicated reaction where we needed a bunch of supplies and generated Succinyl CoA. What happens next?
Well this Succinyl CoA, since we used so much garbage to make it, needs to be cleaved down a bit. Because of that, we need to focus on cleaving it, so no NADH stuff is going to happen.
Using Succinate thiokinase (also called succinyl CoA Synthetase) we cleave succinyl CoA to make Succinate, and due to all of this high energy being released, some nearby GDP turns to GTP.
Succinate has been made, what now?
Succinate feels like it got gipped since the two before it got to make NADH. It’s really immature and wants to make something of it’s own, FADH2.
Succinate oxidizes to fumarate (Sex For) and generates FADH2 from FAD via, you guessed it, an oxidizing reaction using succinate dehydrogenase.
Because this whole damn section is just got to be its own thing, its important to note that this enzyme, succinate dehydrogenase, is the only one in the entire cycle that is in the inner mitochondrial membrane. All the other ones for the whole damn cycle are in the matrix.
Well that last reaction was overly irritating. We have Fumarate now, what does it do?
(For Money?)
That last reaction was too ridiculous. Fumarate doesn’t want to do anything except play in the water. It gets converted to Malate using Fumarase which just adds water across the double bond.
How do we get from Malate back to Oxaloacetate?
We have to make one last carrier, and for nostalgia, we’ll use NAD+ to NADH, and again, a dehydrogenase with an oxidizing reaction.
Malate via malate dehydrogenase to oxaloacetate. This takes electron 7 and 8 from acetyl CoA’s original carbon load, completing the cycle.
How many ATP do we get for each NADH and FADH2 we made?
NADH = 2.5 moles ATP
FADH2 = 1.5 moles ATP
Also recall that we made 1 ATP from the GTP we happened to create with the high energy cleavage of Succinyl CoA
32.5 + 11.5 + 1 = 10 ATP per Acetyl CoA
What vitamins are required for the TCA cycle?
Niacin is required for making the nictinomide portion of NAD
Riboflavin is used for making FAD
Remember the complicated complex we used to make succinyl CoA from alpha ketoglutarate?
- Thiamine needed for Thiamine pyrophosphate
- Pantothenate for CoASH
- Riboflavin for FAD
- Niacin for NAD+
- Lipoic acid is just lipoic acid :)
What other enzyme used a big complex like alphaketoglutarate dehydrogenase?
Pyruvate dehydrogenase, which is the enzyme we use to turn our pyruvate from glycolysis into the acetyl CoA for the TCA cycle
What is special about the enzyme pyruvate dehydrogenase complex?
It has an active and inactive form, which alpha-ketoglutarate dehydrogenase does not.
We deactivate our complex by kinase-ing it, which used an ATP up to accomplish (indicating that ADP and pyruvate would hinder this in that case, we clearly need our ATP to be used elsewhere and have the pyruvate to keep things going) and is stimulated to shut down by NADH and Acetyl CoAm which are products of the reaction.
Phosphatase is used to turn the complex back on, and it is stimulated only by Calcium.
Some of our TCA products/Glycolysis products have side jobs.
Besides Acetyl CoA, what else can Pyruvate turn into for the TCA cycle?
It can use pyruvate carboxylase to turn to oxaloacetate.
We find this in the liver, brain, and fat tissue, and because we are starting one step back, we need a little help, in the form of biotin.
This enzyme is activated by acetyl CoA, which makes since because the more acetyl CoA we have, the more oxaloacetate we need to start the first step of the TCA cycle.
