The Theme of Citric Acid Cycle in Glycolysis and Cellular Respiration
(synonym for Krebs cycle)
At the arcade, after you change your dollar bill into 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. We know all these biology terms and
processes are a lot to handle, so 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 by moving into the citric acid cycle. Sometimes the citric acid cycle is called the Krebs
cycle, after Hans Krebs, the scientist who discovered it and won a Nobel Prize in 1953. Krebs shared the
Nobel Prize that year with Fritz Albert Lipmann, who discovered coenzyme A, which will enter the
pinball machine soon.
In glycolysis, the glucose was oxidized to pyruvate. In the citric acid cycle, the pyruvate will be further
broken down to carbon dioxide. And it will result in more prize tickets (ATP), but we'll also end up with
two other compounds that can be converted to ATP: NADH and FADH2. More on that later.
As we fire up the old pinball machine, we drop a token in and get a ball to start. In the same way you
trade the token for a ball to bounce around the machine, a mitochondrian 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. This step of converting the pyruvate to acetyl CoA, is sometimes called the transition or bridge
step.
The transition step:
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 the pinball game…er, citric acid cycle. 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 at the beginning and end.
Step 1: Our pinball, acetyl CoA, drops its acetyl group, which has two carbons, and the two carbons
combine with a four-carbon compound called oxaloacetate (we won't quiz you on that name), which
make, 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 lost and 2 NADH are formed.
Step 3: The carbon compound pinball resulting from step 2 briefly joins up with coenzyme A, which is
then replaced with a phosphate group. But the phosphate group doesn't stick around long either--one ATP
forms. This is the only ATP made in the citric acid cycle.
Step 4: Our four-carbon pinball loses two hydrogens (which includes their electrons, so it is oxidized).
The hydrogens reduce FAD to FADH2. FAD is a coenzyme (like coenzyme A), and is short for flavin
adenine dinucleotide.
Step 5: The pinball bonds with a water molecule, then gets oxidized with NAD+ on the reducing side,
forming NADH. After all these changes, the pinball is back to a form we saw at the beginning of the citric
acid cycle: oxaloacetate. That's right. All we have to do is drop in another acetyl CoA to spin the wheel
around again.
So what did we get from all this? Only one ATP. But the winnings are better than they seem at first,
because we got three NADH, plus the NADH from converting pyruvate to acetyl CoA. We also got one
FADH2, and we get to multiple everything by two. Why? These compounds came from one pyruvate
molecule, but glucose was broken down into two pyruvate molecules. So our totals for the citric acid
cycle are
• 2 ATP
• 8 NADH
• 2 FADH2
• 6 CO2 (these won't be used for energy like the other products – but don't worry, they don't contribute
much to global warming.)
The NADH and FADH2 are the 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 is also used as a fertilizer. We won't ask
how Hans discovered it.