Ten (Fairly) Detailed Steps to Glycolysis

Glycolysis is a process that cells use to convert glucose, with the aid of two molecules of ATP (adenosine triphosphate) to two molecules of NDAH (reduced nicotinamide dinucleotide amine), four new molecules of ATP and two molecules of pyruvate.

Step 1: Glucose is phosphorylated by ATP and the enzyme hexokinase, to form the sugar phosphate; glucose 6-phosphate with a negative charge, preventing it from travelling through the plasma membrane of the cell, stopping it from escaping. This step also produces one molecule of ATP and a proton. 

Step 2: Isomerization of glucose 6-phosphate occurs; switching the ring form of glucose to its open chain form. This initial part of step two is very reversible, however equilibrium lies to open chain side due to the negative charge on the phosphate (on carbon 6) and the aldehyde on the first carbon. Phosphoglucose isomerase then changes the structure of the sugar phosphate, making a ketone group on carbon 2, thus meaning carbon 1 is left as a hydroxyl group (CH2OH). The resulting molecule being fructose 6-phosphate.

Step 3: The new hydroxyl group is phosphorylated by the second ATP molecule. Phosphofructokinase binds the phosphate group from ATP to the fructose 9-phosphate, creating fructose 1,6-bisphosphate and ADP. The entry of sugars into glycolysis is controlled in this step, through the regulation of the enzyme phosphofructokinase.

Step 4: Next the fructose 1,6-bisphosphate is split up by the aldolase enzyme, making dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. The glyceraldehyde 3-phosphate proceeds immediately through glycolysis.

Step 5: The other molecule made in step 4, dihydroxyacetone phosphate, is isomerized by triose phosphate isomerase in a reversible reaction to form another glyceraldehyde 3-phosphate molecule.

Step 6: A covalent bond is formed between glyceraldehyde 3-phosphate and the -SH side group of the enzyme  glyceraldehyde 3-phosphate dehydrogenase, which binds ionically to NAD+. Oxidation of  glyceraldehyde 3-phosphate occurs as a hydride ion transfers to bound NAD+ forming NADH. Part of the energy released during this process goes towards turning the bond between the enzyme and  glyceraldehyde 3-phosphate into a high energy thioester bond. A molecule of inorganic phosphate displaces the high-energy bond to create 1,3-bisphosphoglycerate containing a high-energy acyl-anhydride bond. 

Step 7:  Next the high energy bond to the phosphate is transferred to ADP to form ATP. Leaving 3-phosphoglycerate.

Step 8: The phosphor ester linkage on 3-phosphoglycerate is moved from carbon 3 to carbon 2 by the enzyme phosphoglycerate mutase, forming 2-phosphoglycerate. 

Step 9: Removal of water from 2-phosphoglycerate with aid of the enzyme enolase creates a high energy enol phosphate linkage, creating phosphoenolpyruvate.

Step 10: Finally the high energy enol phosphate linkage created in step 9 binds to ADP creating ATP and completing glycolysis, and leaving two molecules of pyruvate. 

The result being that 4 molecules of ATP are formed, however the net result is that +2 molecules of of ATP is produces because of the process using up two in steps 1 and 3. Notice that this form of glycolysis is a anaerobic procedure with no mention of molecular oxygen. This has its advantages and disadvantages. Anaerobic glycolysis is a fast procedure, used when cells need to create quick release energy. For example when an athlete jumps the energy will come from glycolysis, and if they continue to perform quick movements anaerobically NADH will not be able to be oxidised to NAD+ (as usually is completed in the citric acid cycle and oxidative phosphorylation). In this instance NADH donates it's electrons to the molecules of pyruvate formed, this creates lactic acid, due to lactic acid being produced by the reduction of pyruvate. This unfortunately leads to the achy feeling after exorcise.

 Conversely glycolysis can not compete with the citric acid cycle, driving oxidative phosphorylation, for producing  ATP. The citric acid cycle provides the respiratory chain with high energy electrons that create a proton gradient supplying ATPase with energy to bond inorganic phosphate to ADP. This, in turn, creates up to 30 molecules of  ATP from just 2 pyruvic acid molecules that are reduced in the citric acid cycle. Showing that aerobic rules the animal world! Sorry homolactic fermentation :( 

Why Cyanide Kills You...

Cyanides (-C≡N) are often found in fruit stones, seeds and bitter almonds in small amounts, but also can be produced by some bacteria and fungi. It is commonly known that most cyanides are highly toxic, but why?


Hydrogen cyanide is an inhibitor of the enzyme cytochrome c oxidase in the fourth complex of the respiratory chain, found in the inner membrane of mitochondria. The binding of a cyanide ion (CN−) and cytochrome c oxidase, stops this enzyme from being able to bind electrons to molecular oxygen, to then bind with protons to make water. Normally the enzyme would translocate H+ ions across the inner membrane in this process, creating a H+ gradient to drive ATP synthase, but this can not be completed because of the presence of the (CN−) on cytochrome c oxidase. As I have described before; ATP synthase catalyses the combination of ADP with inorganic phosphate (like a molecular ferris wheel), creating ATP for molecular energy. Thus now, all aerobic cellular tasks, such as those required in the central nervous system and heart, can not be completed.


When hydrogen cyanide is inhaled, in under 10 minutes, your body will no longer be able to produce the vital energy for life. This will result in death.


Thanks for reading.

H5N1 - 5 mutations to pandemic

The H5N1 virus is deadly to humans, but so far has not gone pandemic, as New Scientist's latest issue explains. H5N1 kills over 60% of the people it infects, the fact is not new, however the potentially leathal concept that 'Five easy steps to bird flu pandemic' coveys is expressed in the title. Research has shown that just 5 mutations in 2 genes has allowed H5N1 to spread between mammals in the lab. Ron Fouchier explained his work at a recent scientific meeting describing that the H5N1 once mutated can "spread as efficiently as the flew". Surely this fact combined with the 60% mortality should strike fear into the public's heart?

Fouchier's research was conducted on ferrets. They first gave H5N1 3 mutations know to adapt the virus to mammals, on giving this to the ferrets they inevitably died, but didn't transfer it on to others. By the tenth time the virus from previous ferrets was given to new ferrets it had mutated many times, and now could spread between them, thus it was air-born. Two further genes were identified as causing H5N1 to spread. 

However Doubts have been expressed towards the validity of these results. It is questionable that we can immediately generalise results conducted on ferrets straight to humans, lessening the worry about the 5 mutation rule 'New Scientist' commits to. On the other hand, ferrets have been proven to have a similar reactions  to virus's that humans  may experience. Still this leaves the statement of 5 mutations unfalsifiable to humans, as the exact mutations needed for the virus to spread between humans would be different. The bottom line is; we have to stay vigilant to the very real threat posed, even if it can not be directly proved that only 5 mutations are needed to start a pandemic in humans, we have to do everything we can not to lose that 60% of the people infected.