How pyruvate from glycolysis is converted to acetyl CoA so it can enter the citric acid cycle. Pyruvate is modified by removal of a carboxyl group followed by oxidation, and then attached to Coenzyme A.
Among the four stages of cellular respiration, pyruvate oxidation is kind of the odd one out; it’s relatively short in comparison to the extensive pathways of glycolysis or the citric acid cycle. But that doesn’t make it unimportant! On the contrary, pyruvate oxidation is a key connector that links glycolysis to the rest of cellular respiration.
Overview of pyruvate oxidation
At the end of glycolysis, we have two pyruvate molecules that still contain lots of extractable energy. Pyruvate oxidation is the next step in capturing the remaining energy in the form of , although no is made directly during pyruvate oxidation.
Simplified diagram of pyruvate oxidation. Pyruvate—three carbons—is converted to acetyl CoA, a two-carbon molecule attached to coenzyme A. A molecule of coenzyme A is a necessary reactant for this reaction, which releases a molecule of carbon dioxide and reduces a NAD+ to NADH.
In eukaryotes, this step takes place in the matrix, the innermost compartment of mitochondria. In prokaryotes, it happens in the cytoplasm. Overall, pyruvate oxidation converts pyruvate—a three-carbon molecule—into acetyl —a two-carbon molecule attached to Coenzyme A—producing an and releasing one carbon dioxide molecule in the process. Acetyl acts as fuel for the citric acid cycle in the next stage of cellular respiration.
Pyruvate oxidation steps
Pyruvate is produced by glycolysis in the cytoplasm, but pyruvate oxidation takes place in the mitochondrial matrix (in eukaryotes). So, before the chemical reactions can begin, pyruvate must enter the mitochondrion, crossing its inner membrane and arriving at the matrix.
In the matrix, pyruvate is modified in a series of steps:
More detailed diagram of the mechanism of pyruvate oxidation.
- A carboxyl group is removed from pyruvate and released as carbon dioxide.
- The two-carbon molecule from the first step is oxidized, and NAD+ accepts the electrons to form NADH.
- The oxidized two-carbon molecule, an acetyl group, is attached to Coenzyme A to form acetyl CoA.
Step 1. A carboxyl group is snipped off of pyruvate and released as a molecule of carbon dioxide, leaving behind a two-carbon molecule.
Step 2. The two-carbon molecule from step 1 is oxidized, and the electrons lost in the oxidation are picked up by to form .
Step 3. The oxidized two-carbon molecule—an acetyl group, highlighted in green—is attached to Coenzyme A (), an organic molecule derived from vitamin B5, to form acetyl . Acetyl is sometimes called a carrier molecule, and its job here is to carry the acetyl group to the citric acid cycle.
The steps above are carried out by a large enzyme complex called the pyruvate dehydrogenase complex, which consists of three interconnected enzymes and includes over 60 subunits. At a couple of stages, the reaction intermediates actually form covalent bonds to the enzyme complex—or, more specifically, to its cofactors. The pyruvate dehydrogenase complex is an important target for regulation, as it controls the amount of acetyl fed into the citric acid cycle.
If we consider the two pyruvates that enter from glycolysis (for each glucose molecule), we can summarize pyruvate oxidation as follows:
- Two molecules of pyruvate are converted into two molecules of acetyl .
- Two carbons are released as carbon dioxide—out of the six originally present in glucose.
- 2 are generated from .
Why make acetyl ? Acetyl serves as fuel for the citric acid cycle in the next stage of cellular respiration. The addition of helps activate the acetyl group, preparing it to undergo the necessary reactions to enter the citric acid cycle.
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- Is this considered anaerobic or aerobic?(11 votes)
- This is aerobic as it involves the Mitochondria where pyruvate oxidation occurs.(28 votes)
- I'm a little confused, it says a carboxyl group is snipped off, which would make sense because then the NAD can be reduced. However it shows no hydrogen in the carboxyl group(11 votes)
- I was confused about this too, but now I know:
The carboxyl group does give the acetyl group a negative charge, but this is not why the NAD+ comes. If you look at the illustration, it shows the CoA attached to sulfur and Hydrogen in step 2. The NAD+ comes to snatch up a H ion that the CoA-SH left.(23 votes)
- Does the pyruvic acid required for krebs cycle come from glycolysis??(4 votes)
- Yep, the pyruvate becomes Acetyl CoA after losing a carbon molecule. Then it joins with Oxaloacetate to get into citrate cycle.(12 votes)
- What exactly is NAD+ and NADH? And what are they made of, I have asked my bio teacher but he doesn't really answer in depth. Sorry I know it may seem like a stupid question but I find myself confused on this stage.(7 votes)
- https://upload.wikimedia.org/wikipedia/commons/thumb/b/b5/NAD_oxidation_reduction.svg/250px-NAD_oxidation_reduction.svg.png NADH is a molecule that can donate a hydrogen atom and the electrons to go along with it, NAD+ can accept a hydrogen atom and its electrons.(2 votes)
- What causes the carboxyl group of the pyruvate to be removed?(3 votes)
- The enzyme 'pyruvate dehydrogenase' pulls away the carboxyl group, resulting in the release of Carbon Dioxide, leaving the Acetyl group behind for binding with CoA.(5 votes)
- My textbook states that the pyruvic acid is first converted into acetic acid before being oxidized. This conflicts with what is being presented here. What is going on?
Furthermore, my textbook states this occurs in the cristae of the mitochondria — while this site claims it happens in the matrix...(2 votes)
- Definitely happens in matrix. This site is correct.(6 votes)
- Why is NADH formed when NAD+ is reduced, gained electrons? Shouldn't it be NAD with no charge or NAD- with a proton kicked out? Furthermore, where did the hydrogen to build NADH come from?(4 votes)
- The bicarbonate buffer system is what creates H ions. Our body recycles 70% of CO2 by hydrolysis. CO2 and H2O convert into carbonic acid H2CO3 and immediately get broken down into H and HCO3(2 votes)
- What general key things do I need to know for each step of the Krebs cycle?(3 votes)
- usually the enzymes and intermediates are most important, and also the by-products released, ie, the NADH, FADH, and GTP(3 votes)
- What does the structure of Co-enzyme A look like?(2 votes)
- CoA consists of an adenine nucleotide base attached to a ribose 5 carbon sugar, from which is attached a chain of 2 phosphate molecules (as in ADP). The enzyme protein comes next on the chain, followed by a covalently bonded sulphur molecule, which is then lastly attached to the removable functional group, the acetyl group -COCH3(4 votes)
- What role does Coenzyme A play in the potential energy of CoA? :/(3 votes)
- Roles of CoA are:
1. synthesis and oxidation of fatty acids
2. oxidation of pyruvate
Not sure about potential energy, but it has that power to oxidize its substrate (such as acetyl group) and transfers H+ to NAD+ in order to reduce it.(1 vote)