The Basics of Energy Production: Glycolysis

Step 1

The first step of glycolysis is catalyzed by an enzyme called hexokinase. This process begins by adding two phosphate groups from two ATP to a glucose molecule (C₆H₁₂O₆). As the glucose molecule is phosphorylated it produces glucose-6-phosphate, which is a more reactive form of glucose. This also keeps glucose inside the cell because glucose with a phosphate cannot cross the plasma membrane. 

Step 2

The second phase of glycolysis is catalyzed by isomerase. In this step, a glucose-6-phosphate (C₆H₁₃O₉P) is converted into its isomer, fructose-6-phosphate. 

Step 3

The third step utilizes an enzyme called phosphofructokinase that phosphorylates (adds a phosphate) fructose-6-phosphate (C₆H₁₃O₉P) to produce fructose-1,6-biphosphate.

Not only does phosphofructokinase drive this pathway, but it also regulates the speed at which this reaction occurs. The enzyme is more active when ADP levels are elevated and slows down with sufficient concentration of ATP. 

Step 4

The fourth step of glycolysis is catalyzed by an enzyme called aldolase which splits fructose-1,6-biphosphate (C₆H₁₄O₁₂P₂) into two three-carbon molecules; dihydroxyacetone-phosphate (DHAP) and glyceraldehyde-3-phosphate. From these two, only glyceraldehyde-3-phosphate is able to directly continue to the next phase of glycolysis. 

Step 5

The fifth and last step of the energy-requiring phase is catalyzed by triosephosphate isomerase. This enzyme transforms DHAP into its isomer, glyceraldehyde-3-phosphate. This effectively continues the pathway with two molecules of the same isomer. 

At this point, two ATP molecules are used to break down a single molecule of glucose. 

Step 6

The sixth step of glycolysis oxidizes the sugar (glyceraldehyde-3-phosphate) with the help of an enzyme called glyceraldehyde-3-phosphate dehydrogenase. This process also releases high-energy electrons that are picked up by the electron carrier NAD⁺, reducing it to NADH and H⁺. Then, a second phosphate is added to the sugar, which phosphorylates it into 1,3-biphosphoglycerate. 

Note that the continuation of this reaction depends on the availability of the oxidized form of the electron carrier (NAD⁺). Therefore, NADH must constantly be oxidized back to NAD⁺ to maintain this process.

In aerobic conditions, NADH can be oxidized and the electrons from the released hydrogen can be used to generate ATP. In anaerobic conditions (without oxygen) the pathway continues by fermentation. This also produces NAD⁺ from NADH. 

Step 7

The seventh step is catalyzed by phosphoglycerate kinase, which causes 1,3-bisphosphoglycerate (C₃H₈O₁₀P₂) to donate one of its phosphate groups to ADP. This forms a single molecule of ATP as well as 3-phosphoglycerate. 

Step 8

Step eight of glycolysis is catalyzed by a mutase enzyme. Here, the remaining phosphate group of 3-phosphoglycerate (C₃H₇O₇P) is transferred from the third carbon to the second carbon. Thus, converting 3-phosphoglycerate into its isomer, 2-phosphoglycerate. 

Step 9

The ninth step is catalyzed by enolase, which causes 2-phosphoglycerate (C₃H₇O₇P) to lose its water molecule. This dehydration reaction produces phosphoenolpyruvate (PEP).

Step 10

The final step of glycolysis is catalyzed by the enzyme pyruvate kinase. In this stage, phosphoenolpyruvate (C₃H₅O₆P) donates its phosphate group to ADP, creating a second molecule of ATP. As PEP loses its phosphate, it is converted into pyruvate which is the end product of glycolysis. 

Because pyruvate kinase is a rate-limiting enzyme that catalyzes the production of pyruvate, this last step will not occur if it is not available in sufficient quantities. While this still allows glycolysis to continue, it only produces two ATP molecules during the energy-releasing phase. 

What happens to pyruvate?

In aerobic conditions, pyruvate can be oxidized in the mitochondria to produce a total of two ATP. This process also produces Acetyl-CoA, which enters the citric acid cycle, further continuing the breakdown of glucose. Keep in mind that to fully oxidize a glucose molecule, the muscles must have a sufficient supply of oxygen. In practice, this means that ATP can be produced with oxygen as long as the intensity of the exercise remains low enough.

In anaerobic conditions, ATP must be produced through fermentation. Here, pyruvate molecules are reduced to lactate by NADH, leaving NAD⁺ as a byproduct. Through a process known as the Cori cycle, the lactate produced by the muscles is transported to the liver and converted back to glucose (gluconeogenesis), and sent back to the muscles. Anaerobic respiration takes over during shorter and more intense exercises when the muscle’s oxygen need surpasses the oxygen supply. 

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