From Glucose To ATP
Generating ATP from glucose is one the most incredible processes our body executes, It is one of the most fundamental and important functions in our human body and is key to understanding BioEnergetics.
By looking at the glucose formula - C₆H₁₂O₆ ,We can see it has:
6 Carbons that acts as the structural skeleton of the molecule.
12 Hydrogens which hold the actual energy and will be delivered to NAD/FAD to enter the Electron transport chain.
6 Oxygens creating it's polarity, making it water soluble and allow the formation of CO₂.
That special structure & formula of glucose are not random, Organisms for millions of years have created glucose using water, CO₂ and light.
6CO₂ + 6H₂O + light energy → C₆H₁₂O₆ + 6O₂
We as humans do the exact opposite and break glucose to water & CO₂ using oxygen, all for the purpose of generating ATP.
To be precise each Glucose molecule is oxidized by 6 molecular oxygens and generate 6 molecules of CO2, 6 molecules of water and 32-36 ATP
C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O + 32 ATP
When glucose is ingested it's carried from the intestine to the blood by SGLT1(Sodium-Glucose Linked Transporter).
Then 5 transporters: GLUT 1-5 carries it into the cell.
Glucose Oxidation has 2 main goals, The first is to get converted into 2 Pyruvate molecusles, Then the pyruvate to enter into the krebs cycle to get fully oxidized.
We begin in the cytosol where a Phosphate group get added to glucose to lock it into the cell and prevent it from escaping
Now we convert Glucose-6-Phosphate into Fructose-6-Phosphate, This step is preperation for adding another phosphate group later.
Now we can add another Phosphate group which is crucial for getting 2 Pyruvates and not 1.
Now we have 2 Phosphate Groups and we can break the molecule to half.
We'll get DHAP(A keton) from carbons 4-6 and G3P(An Aldehyde) from carbons 1-3.
DHAP will get converted to G3P, a key step towards Pyruvate.
Now we have 2 molecules of G3P, a 3 carbon molecules just like pyruvate, G3P is Aldehyde with high energy phosphate.
In 5 steps it will become Pyruvate:
1. G3P is oxidized and phosphorylated to 1,3-bisphosphoglycerate by G3P dehydrogenase, producing 1 NADH per G3P. This is a special step, phosphate group is added without the need of ATP as usual due to the energy released when the aldehyde group is oxidized to a carboxylic acid.
2. 1,3-Bisphospho-glycerate donates a high-energy phosphate to ADP, forming 3-phospho-glycerate, generating 1 ATP per G3P via phosphoglycerate kinase.
3. 3-Phospho-glycerate is converted to 2-phosphoglycerate (2-PG) by phosphoglycerate mutase.
4. 2-Phosphoglycerate is dehydrated to phosphoenolpyruvate (PEP) by enolase, creating a high-energy enol phosphate, releasing water molecule.
5. Phosphoenolpyruvate donates its phosphate to ADP, forming pyruvate and generating 1 ATP per G3P via pyruvate kinase.
From Glucose to Pyruvate we generated:
2 ATP + 2 NADH Molecules.
Pyruvate
We arrived to an important junction: Pyruvate can be converted to acetyl-CoA and enter the Krebs cycle if the NAD⁺/NADH ratio is high, there is sufficient vitamin B1, and oxygen is available. If these conditions are not met, pyruvate is converted to lactate, a toxic product that inhibits oxygen use and produces much less ATP than the Krebs cycle.
The enzyme PDH takes pyruvate and converts it into acetyl and connects it
Co Enzyme A, a large transport molecule that delivers the Acetyl to the krebs cycle.
Pyruvate + CoA + NAD⁺ → Acetyl-CoA + NADH + CO₂
This means we generated another:
2 NADH + 2 CO2
The Krebs Cycle
The Krebs cycle is a cyclic process occurring in the mitochondria that in each round receives an acetyl molecule and passes it through 8 steps. These steps gradually strip away the hydrogens and release carbon dioxide, The Krebs Cycle it is the primary source for electrons to the Electron Transport Chain.
1.Acetyl CoA connects with oxaloacetate to form citrate a six carbon molecule.
2.Citrate is turned into isocitrate by aconitase.
3.Isocitrate is oxidized and decarboxylated to alpha ketoglutarate forming NADH, and one carbon is released as CO₂.
4. A-ketoglutarate is oxidized and decarboxylated to succinyl producing another NADH and CO₂. succinyl a four carbon skeleton is linked again to CoA.
5. Succinyl CoA is converted to succinate. The high energy bond is broken and its energy is used generating ATP , CoA is released.
6.Succinate is oxidized to fumarate. Electrons are removed from succinate and transferred to FAD, forming FADH₂. This step is directly linked to the electron transport chain.
7.Fumarate is hydrated to malate. No redox reaction occurs in this step.
8.Malate is oxidized to oxaloacetate, electrons are transferred to NAD⁺ forming NADH, and the original four carbon oxaloacetate is regenerated, allowing the cycle to continue.
In the krebs cycle Each acetyl CoA create
2 CO₂ +3 NADH +FADH₂ + ATP.
From Glucose to Pyruvate we generated: 2 ATP + 2 NADH Molecules.
Pyruvate to AcetylCoA we generated: 2 NADH + 2 CO2
In total
10 NADH --> 25 ATP + 2 FADH --> 3 ATP + 4 ATP = 32 ATP
And 6 CO2
To see how NADH and FADH gets converted to ATP continue to this article.