At the arcade, after you exchange your dollar bill for tokens, you set your sights on a game. In a cell, if oxygen is present, the pyruvate from glycolysis heads over to a mitochondrion for the citric acid cycle. If no oxygen is in the house, then skip right along to fermentation (that game isn't for us right now, so keep reading). Also, we know all these biology terms and processes are a lot to handle, but don't worry. We got you covered.

In this installment of the cellular respiration saga, we will finish up the oxidation of the glucose molecule we started with (which is now two pyruvate molecules) by moving into the citric acid cycle.

The citric acid cycle goes by many names. It's so vital to energy production that everyone wanted a chance to label it. So don't get your knickers in a twist if you hear about something called the Krebs cycle. No, you didn't miss a reading assignment.

Hans Krebs, a German scientist, first discovered this marvel of biochemical processes, winning a Nobel Prize in 1953 for his work. Krebs shared the Nobel Prize that year with Fritz Albert Lipmann, who discovered coenzyme A. And just because they can, biologists also will refer to the Krebs…er, we mean citric acid cycle, as the TCA cycle. TCA refers to tricarboxylic acid, but TCA has a nicer ring to it.

In glycolysis, glucose is oxidized to pyruvate. In the citric acid cycle, the pyruvate will be further broken down to carbon dioxide. This will result in more ATP (think cellular prize tickets), but we'll also end up with two other compounds that can be converted to ATP: NADH and FADH₂. More on that later.

To fire up an old pinball machine, you drop a token in and get a ball. In the same way you trade the token for a ball to bounce around the machine, a mitochondrion changes pyruvate to a compound called acetyl-CoA, short for acetyl coenzyme A. A coenzyme is a helper molecule that binds to an enzyme and is necessary for that enzyme to function.

Acetyl-CoA is the compound that enters the citric acid cycle. The step of converting the pyruvate to acetyl-CoA is called the transition step, and it goes a little something like this:

1. Pyruvate loses a molecule of CO₂.
2. NAD⁺ oxidizes pyruvate, which makes acetate.
3. Acetate is joined by coenzyme A, making acetyl-CoA.

Now for some citric acid pinball. Get those reflexes ready. At each stage of the cycle, the carbon compound we're calling the pinball has a different name. We're not going to worry about those names here, except for the ones at the beginning and end of the process.


Time to turn those tokens into tickets and win some ATP (Source)


The inner workings of the citric acid cycle

Step 1. Our pinball, acetyl-CoA, drops its acetyl group, which has two carbons. The two carbons combine with a four-carbon compound called oxaloacetate (we won't quiz you on that name), which makes, ta-da, citric acid.

Step 2. Citric acid is oxidized and loses a carbon dioxide (CO₂) molecule. The electron it loses goes on to reduce NAD⁺ to NADH. Then this happens again. Yup, it happens two times, meaning two CO₂ molecules are made and two NADH are formed.

Step 3. The carbon compound resulting from Step 2 briefly joins up with coenzyme A. Coenzyme A then gets bumped off and is replaced with a phosphate group. The phosphate group jumps ship and meets up with an ADP molecule to make one ATP. This is the only ATP made in the citric acid cycle.

Step 4. Our four-carbon pinball loses two hydrogen atoms (which includes their electrons, so it is oxidized). The hydrogens reduce FAD²⁺ to FADH₂. FAD²⁺, a coenzyme, is short for flavin adenine dinucleotide (gesundheit).

Step 5. The pinball bonds with a water molecule and is then oxidized when NAD⁺ snags an electron. NAD⁺ is reduced to NADH. After all these changes, the pinball is back to the same molecule we saw at the beginning of the citric acid cycle: oxaloacetate. That's right. We went full circle. Guess that's why it's called a cycle. All we have to do is drop in another acetyl-CoA to send our pinball whizzing around again.

So what did we get from all this? One lousy ATP. But wait, there's more! What else did we win? We got three NADH molecules, plus the NADH from converting pyruvate to acetyl-CoA. We got one FADH₂, and on top of all these molecular prizes, we doubled our points. Why? Recall that we started our game with not one but two pinballs, because glucose is broken down into two pyruvate molecules during glycolysis.

The Krebs cycle is an aerobic process, but did you notice any oxygen anywhere? Prepare to have your mind blown. The process we'll learn about next, oxidative phosphorylation, requires oxygen as the terminal electron acceptor, and the results of that process feed back into this one. If we don't have oxygen, then we can't do the next step in the process, which means we can't circle around back to this step, which means we've tilted the pinball machine and are waiting for a reset.

Having oxygen around means that we can regenerate NAD⁺ from NADH. That's important because we need NAD⁺ to oxidize pyruvate to acetyl-CoA in the transition step, and then again in Step 2 of the Krebs cycle to oxidize citric acid.

To recap, our totals for the citric acid cycle are:

• 2 ATP
• 8 NADH
• 2 FADH₂
• 6 CO2

The NADH and FADH₂ are bonus tokens for the next round of cellular respiration pinball, oxidative phosphorylation.

Brain Snack

In addition to figuring out the citric acid cycle, Hans Krebs also discovered the urea cycle, which produces urea. Urea is excreted from animals' bodies in pee. It's also used as a fertilizer. We won't ask how Krebs discovered it.