View Full Version : Glycolysis

30th May 09, 05:34 PM
Glycolysis (http://en.wikipedia.org/wiki/Glycolysis) is undoubtedly one of the earliest metabolic pathways to develop. It has been conserved in all living things whether they use it for their primary energy production needs or not. It uses no complicated organelles and happens freely in the cytoplasm of a cell to produce chemical energy in the form of ATP as long as glucose is present. Though relatively inefficient, capturing only 3.5% of the total energy in glucose’s bonds, it was a major breakthrough in the development of metabolism in life on earth. Using a series of enzyme mediated reactions, glucose is phosphorylated, broken into two molecules of pyruvate and the energy from the broken bonds is used to make adenosine triphosphate (ATP) (http://en.wikipedia.org/wiki/Adenosine_triphosphate), a cell’s primary energy source. All life on earth uses ATP for their energy needs; glycolysis is just one way of producing it. In fact, the two pyruvate molecules left still contain most of the energy in the glucose molecule and are further reduced in other pathways such as Kreb’s cycle (http://en.wikipedia.org/wiki/Krebs_cycle) and the electron transport chain (http://en.wikipedia.org/wiki/Electron_transport_chain). Though its contribution to the overall energy production of a eukaryotic cell is smaller than other systems, it is a remarkably beautiful system in its control and fulfillment of the basic need to have a steady and reliable method of producing energy. My goal with this article is to give a simplistic description of the changes in a glucose molecule and the role the system has in our metabolism. Chemical names aside, I want to describe it so that you can understand the basics without being drawn into the discouraging pit that is scientific jargon.


Used by all life on earth to power essential functions, ATP contains high energy phosphate bonds. The red phosphate group is the one with the greatest energy, releasing 7.3 kcal/mol, which is more than enough to power most reactions in a cell.

The first reactions use two ATP to prime the reaction by readying the molecule of glucose for cleavage. Enzymes (http://en.wikipedia.org/wiki/Enzyme) take the ATP molecules and break the third phosphate bond changing ATP into ADP (adenosine diphosphate). With the release of energy to prime the reaction and the phosphate ions free the glucose is phosphorylated twice and rearranged to make fructose 1,6 biphosphate.


It is now ready for cleavage and broken into two three-carbon molecules. These are glyceraldhyde 3 phosphate and one that closely resembles it: dihydroxy acetone phosphate. These are then phosphorylated again and converted into the same molecule: biphosphoglycerate (BPG). There are now 2 molecules of BPG, each with two phosphate groups capable of doing the same reactions. Though it doesn’t have an active role in glycolysis, one very important thing occurs: electrons attached to certain hydrogen atoms are taken and given to an electron carrier called NAD+ (http://en.wikipedia.org/wiki/NAD%2B). As NADH, they are then ferried to a set of proteins in the mitochondria (http://en.wikipedia.org/wiki/Mitochondria)lovingly called the electron transport chain (http://en.wikipedia.org/wiki/Electron_transport_chain). I’ll explain what this is in detail later, but for now understand that it is basically another ATP production method and these energetic hydrogens play an important role in it.


The BPG products are used as fuel for the next set of reactions, which actually produce the ATP. They accomplish this by what is known as substrate level phosphorylation (http://en.wikipedia.org/wiki/Substrate_level_phosphorylation). This is a coupled enzyme reaction, where the reaction site is the enzyme itself. The enzyme brings two molecules close enough so they can react and in this case trade pieces like a phosphate ion. The chemicals in this step are the phosphorylated piece of glucose (BPG) and an ADP molecule. This also occurs with another product in the chain in the same enzymatic fashion. Under the direction of the enzyme BPG gives a phosphate ion to an ADP molecule making an ATP. Over the course of the whole system, this is done a total of 4 times, yielding 4 ATP molecules.

After the ATP is made the next product in the chain released is 3-phosphoglycerate, which still has a high energy phosphate bond that can be used to make ATP. The problem, though, is enzymes are very specific in what they bond to, so it must be changed once again into a usable shape. Thus, the molecule is changed first into 2-phosphoglycerate and then into phosphoenol pyruvate (PEP). From here one more round of ATP production can begin. PEP gives its last phosphate ion to another ADP molecule releasing ATP. The last product of this system is pyruvate, which still contains a good deal of energy. It is moved to another energy production system called Kreb’s cycle where even more energy is abstracted from its bonds.


At the end, a total of 4 ATP were produced, 2 NAD+ ions were given electrons and hydrogen atoms for the electron transport chain and 2 pyruvate molecules were sent to Kreb’s cycle. The system started by using up 2 ATP to initially phosphorylate the glucose molecule, but made 4 ATP for a net gain of 2 ATP. All in all not a bad piece of work. Get Wall Street on the line: cells make better bankers.

Next time: Kreb’s cycle.

31st May 09, 01:11 AM
Thank you for putting this up here. I am fascinated with anything related to early life, and while I don't want to derail at all, do you know what role glycolysis plays in understanding abiogenesis?

31st May 09, 02:37 AM
well, there are theories on how that developed and I have an article I'm already writing on it. If you wait a couple of days I'll iron it out and post it up. Sunwukong had a question about a similar topic a bit ago, but I never got a change to finish it.

A quick answer would be ATP was chosen first as the chief energy molecule, that alone gave the little guys reliable access to energy, then probably glycolysis or some other means of producing ATP. Other pathways seem to have been derived as ways of getting even more energy out of it. Kreb's cycle, for example, utilizes the pyruvate at the end as starting material for its production. Also, further down the line, the electron transport chain uses the H/e- (mentioned above) to produce a shit load of ATP via diffusion gradients and specialized membrane proteins.

I'll put up the metabolic evolution one before kreb's cycle, etc

1st June 09, 07:39 AM
I want to add a little more about NAD+, that's a really important part of the process for a couple of reasons. In writing it things got cut out to make it easier to understand the process of it, but I don't think its a good idea to leave this out.
Let's inspect the general reaction:

Glucose + 2Phosphates + 2 ADP + 2 NAD+ ------------------->
2Pyruvate + 2NADH + 2ATP + 2H+ + 2 H2O

NAD+ is a useful electron acceptor. During glycolysis a hydrogen atom and two electrons are taken from G3P and are used to reduce the charge on NAD+ by forming a bond. The NADH ferries these to the electron transport chain and drops the kiddies at the pool. There's one problem though: what to do with that hydrogen atom? Cells have a limited supply of NAD+; for glycolysis to continue there needs to be a way to recycle the NAD+ and find a way to get rid of the hydrogen at the end of the chain.

Cells accomplish this two ways: by aerobic respiration (http://en.wikipedia.org/wiki/Aerobic_respiration) and/or fermentation. With Aerobic respiration, cells use oxygen as the final acceptor for that hydrogen. The NADH donate this hydrogen to oxygen to form water, a good nontoxic, easily removable product. You may have already heard of fermentation with the production of alcohol. This is a similar process, except the yeasts that poison our delicious beverages produce ethanol as a toxic byproduct. Much like those yeasts, when our cells are deprived of oxygen they use an organic molecule as the receiver of this hydrogen atom, in particular the pyruvate released at the end of glycolysis. The pyruvate is further reduced to lactic acid (http://en.wikipedia.org/wiki/Lactic_acid), which is usually misrepresented as the cause of muscle fatigue during or after exercise.

Cells have a limited supply of NAD+; for glycolysis to continue there needs to be a way to recycle the NAD+ and find a way to get rid of the hydrogen at the end of the chain.

Think this over, this is why you breathe air.