Explaining Simply: The Krebs Cycle
While glycolysis (splitting glucose) is a relatively simply reaction, the kreb’s cycle, aka the citric acid cycle, aka tricarboxylic acid cycle, aka the TCA cycle is a bit different. Just ask any medical student. But unlike what the image below might seem, if you break it down into its building blocks it’s much easier to understand.
Also, if you’re someone who has to memorize it at the end I’ve given a method that might help.
If you’re someone who doesn’t know much about biology, don’t worry about the meanings of the names, focus more on the general process and what each thing does.
Fun fact
The Krebs cycle by itself doesn’t actually make much energy directly. Instead it makes NADH (nictotineamide adeninde dinucleotide and hydrogen) and gives it to the mitochondria, the powerhouses of the cell to make most of the energy.
Summary
The Krebs cycle is right after glycolysis, and 1 glucose molecule causes 2 rounds of production. Like a production line, it takes the product of the previous step and does something to it, making things like 2 CO2 molecules, 3 NADH, 1 FADH (flavin adenine dinucleotide and hydrogens), and 1 ATP after all 8 steps. For each step it needs special equipment, like different machines in a factory. These are the specific enzymes.
It also makes a lot of things that aren’t used to make ATP and instead are given to other parts of the cell to do things with. Like a factory giving its scrap iron to someone else to melt down and make something useful. But instead of scrap iron it’s something like succinyl CoA used to help make hemoglobin.
It’s essential for eukaryotic life because indirectly it makes a lot of ATP (basically cell money). By itself it only makes 1 ATP per round of production, but includes the mitochondria and it can make 12 ATP per round of production.
Like a production line it wants to maximize efficiency, so the final product is used to restart the cycle all over again.
Details & Clarifications
Before going through the 8 steps in detail, you should know that acetyl CoA (CoA is short for coenzyme A) is made by oxidizing pyruvate, meaning removing electrons [2, 3]. Acetyl CoA is the starting material, you can think of it like a raw good.
Now to go through the 8 steps in a bit of detail.
In the first, acetyl CoA with oxaloacetate (a 4 carbon sugar) are used to make citrate (a 6 carbon sugar) [2, 3]. Going back to the factory analogy, you can think of it like a circular conveyor belt, where the thing at the end is reused in the process to save money. And the machine that makes citrate is citrate synthase [2, 3].
If you forget what happens in a reaction, look at the machine, the enzyme. Synthase is just another word for making, and “citrate synthase” is like saying citrate making. So if you ever see an enzyme with synthase in the name, remember that it makes the first part of the name.
In the second, citrate loses water and turns into isocitrate (a 6 carbon sugar) [2, 3].
This is also the slowest step in the production line [1]. Meaning it’s the rate limiting step, in other words the speed of this step decides the speed of the whole cycle [1]. Like in a production line, it doesn’t matter how fast the other steps are, the first step will have to slow down while the steps after others will be waiting on this step to finish so they can do their job.
The third step is turning isocitrate to alpha-ketoglutarate (a 5 carbon sugar) [2, 3]. The machine that does this is the enzyme isocitrate dehydrogenase [2, 3]. It went from a 6 carbon sugar to a 5 carbon sugar. You can remember it by the enzyme, Isocitrate dehydrogenase. It sounds like dehydrate. And when you dehydrate something you take away water, in this case instead of water it’s a carbon atom. But where did it go? Well some other things are made here, CO2 (where the carbon went) and NADH [2, 3]. You can think of NADH like a box of batteries. It doesn’t power things itself, but carries the things that do.
The fourth step is turning alpha-ketoglutarate into succinyl CoA (a 4 carbon sugar) [2, 3]. The machine that does this is alpha-ketoglutarate dehydrogenase [2, 3]. Doing what happens in step 3 but with alpha-ketoglutarate. And again, CO2 and NADH are also made.
You might be wondering why the same enzyme from step 3 can’t be reused here in step 4. Well in a factory each machine can only work with 1 thing, it could be bottling, but it can only do that and only with a specific kind of bottle. It’s similar with enzymes, they can only work with specific material and not much else.
The fifth step is replacing the CoA in succinyl CoA with a phosphate (PO4) to make succinate [2, 3]. But this PO4 quickly goes to ADP to make ATP (the real money of the cell) [2, 3]. It can also turn GDP to GTP in some organisms, but it’s rare.
The sixth step is turning succinate to fumarate (another 4 carbon sugar) [2, 3]. This also makes FADH2 [2, 3]. FADH2 is like a worse NADH, you use it because you have to, not want to. But why don’t you make NADH? Well it’s because succinate is greedy for electrons, it doesn’t really want to give them, so NADH can’t be used [2]. But FAD2+ is even greedier than succinate, so it gets the electrons and 2 hydrogen atoms and becomes FADH2 [2].
The seventh step is adding water to fumarate to make malate [2, 3]. The machine that does this is the enzyme fumarate hydratase [1]. Like before, the part ending in “-ase” does something to the thing before it. Hydratase sounds like hydrate, so this enzyme hydrates fumarate.
The eighth step is oxidizing malate to oxaloacetate, which also makes another NADH in the process [2, 3]. The machine that does this is malate dehydrogenase.
So we’ve come full circle, oxaloacetate is made and ready to go back into the circle, and we have 2 CO2 molecules, 3 NADH, 1 FADH2, 1 ATP, and 3 hydrogen atoms. But what are we going to do with them? Well the CO2 is just waste. No factory is perfect and will always make at least some waste. But the rest? NADH and FADH2 will go to another factory, the powerhouses of the cell the mitochondria. There they will make the real money of the cell, ATP, and plenty of it! Meanwhile the ATP made will be spent, because like our current economy money needs to be spent for it to work.
But it’s only been 1 round of production, 1 glucose makes 2 rounds. So it’s time for another round!
But what if you have enough energy and don’t need much more? How do you prevent a power surge? Or in this case ATP inflation? Luckily there are safeguards! One is NADH itself, the more NADH there is the slower the Krebs cycle is because it inhibits the cycle [1]. Imagine NADH as heat, the more there is, the hotter the machine and working environment gets, and eventually you have to stop to prevent the machine from overheating and the workers from being put in danger.
Even before the Krebs cycle this exists, where acetyl CoA actually slows the making of more acetyl CoA.
In fact a lot of biology actually does this, where something made actually slows the process that makes it. This way if there’s enough of the product, less and less will be made until more of it is needed.
Memorization Tips
This is from personal experience, so it may not work for you, just a heads up. To memorize you could try looking at first the reactants, then saying aloud or writing down the steps in order, checking each one after doing it. If you get it wrong, correct it and start from the beginning. Then include the enzymes, and if you make any mistake, no matter what or where it is, correct yourself and restart from scratch.
That or you could memorize it step by step. So look at the first step, write or say it, then the second, repeat from step 1. That way you’re reinforcing the steps you’ve already done as you go through the cycle.
Again, this has just personally worked for me, it may not for you. Just try it and see if it works, if it doesn’t then stop doing it.
References & Further Reading
[1] Alabdyladhem, Tamin O., and Bruno Bordoni. “Physiology, Krebs Cycle.” National Libary of Medicine, https://www.ncbi.nlm.nih.gov/books/NBK556032/.
[2] “The Citric Acid Cycle | Cellular Respiration (Article).” Khan Academy, Khan Academy, https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/pyruvate-oxidation-and-the-citric-acid-cycle/a/the-citric-acid-cycle.
[3] Kaiser, Gary E. “II. BACTERIAL GROWTH AND MICROBIAL METABOLISM.” The Community College of Baltimore County, Catonsville Campus, https://cwoer.ccbcmd.edu/science/microbiology/lecture/unit7/metabolism/cellresp/cac.html.
