CHAPTER 22: Unit 4. Glycolysis: Oxidation of Glucose

The major source of energy for the body is the glucose produced when we digest the carbohydrates in our food or from glycogen, a polysaccharide stored in the liver and skeletal muscle. Glucose in the bloodstream enters our cells where it undergoes degradation in a pathway called glycolysis. Glycolysis is anaerobic process, no oxygen required. Glycolysis is a series of reactions by which six-carbon glucose is converted into three-carbon keto-acids (pyruvate). Glucose is trapped by phosphorylation, with the help of the enzyme hexokinase. Adenosine triphosphate (ATP) is used in this reaction and the product, glucose-6-P, inhibits hexokinase.

Glycolysis is used by all cells in the body for energy generation. The final product of glycolysis is pyruvate in aerobic settings and lactate in anaerobic conditions. Pyruvate enters the Krebs cycle for further energy production.

In glycolysis the six-carbon glucose molecule is degraded to yield two three-carbon pyruvate molecules. A net of two ATP is produced along with two NADH.Reference: http://www2.csudh.edu/nsturm/CHE452/01_Glycolysis.htmGlycolysis involves distinct reactions that convert glucose into pyruvate. In this section, we will cover the first four of these reactions, which convert glucose into glyceraldehyde-3-phosphate. Glucose is a six- membered ring molecule found in the blood and is usually a result of the breakdown of carbohydrates into sugars. It enters cells through specific transporter proteins that move it from outside the cell into the cell’s cytosol. All of the glycolytic enzymes are found in the cytosol.Reaction 1: PhosphorylationIn the first step of glycolysis, the glucose ring is phosphorylated. Phosphorylation is the process of adding a phosphate group to a molecule derived from ATP. As a result, at this point in glycolysis, 1 molecule of ATP has been consumed.

The reaction occurs with the help of the enzyme hexokinase, an enzyme that catalyzes the phosphorylation of many six-membered glucose-like ring structures. A kinase is the name given to an enzyme that phosphorylates other molecules. Atomic magnesium (Mg) is also involved to help shield the negative charges from the phosphate groups on the ATP molecule. The result of this phosphorylation is a molecule called glucose-6-phosphate (G6P), thusly called because the 6′ carbon of the glucose acquires the phosphate group.Reaction 2: Phosphoglucose IsomeraseThe second step of glycolysis involves the conversion of glucose-6-phosphate to fructose-6-phosphate (F6P). This reaction occurs with the help of the enzyme phosphoglucose isomerase (PI). As the name of the enzyme suggests, this reaction involves an isomerization reaction.

Reaction 3: PhosphofructokinaseIn the third step of glycolysis, fructose-6-phosphate is converted to fructose- 1,6-bisphosphate (FBP). Similar to the reaction that occurs in step 1 of glycolysis, a second molecule of ATP provides the phosphate group that is added on to the F6P molecule.

Reaction 4: Cleavage (Aldolase)This stage of glycolysis utilizes the enzyme aldolase, which catalyzes the cleavage of FBP to yield two 3-carbon molecules. One of these molecules is called glyceraldehyde-3-phosphate (GAP) and the other is called dihydroxyacetone phosphate (DHAP).

Reaction 5: Triosephosphate isomeraseBecause the dihydroxyacetone phosphate is a ketone,  it cannot react further. However, it undergoes isomerization by the enzyme triosephosphate isomerase, a second molecule of glyceraldehyde 3-phosphate (GAP) which can be oxidized. Now all six carbon atoms from glucose are contained in two identical trios phosphates.

Reaction 6: Energy-Generating (Glyceraldehyde-3-phosphate Dehydrogenase)

Glyceraldehyde-3-phosphate is oxidized by the coenzyme nicotinamide adenine dinucleotide (NAD); 2) the molecule is phosphorylated by the addition of a free phosphate group. The enzyme that catalyzes this reaction is glyceraldehyde-3-phosphate dehydrogenase (GAPDH) producing 1,3 bisphoglycerate, NADH, and a hydrogen atom. Reaction 7: Phosphate Transfer      In this step, 1,3 bisphoglycerate is converted to 3-phosphoglycerate by the enzyme phosphoglycerate kinase (PGK). This reaction involves the loss of a phosphate group from the starting material. The phosphate is transferred to a molecule of ADP that yields our first molecule of ATP. Since we actually have two molecules of 1,3 bisphoglycerate (because there were two 3-carbon products from stage 1 of glycolysis), we actually synthesize two molecules of ATP at this step. With this synthesis of ATP, we have cancelled the first two molecules of ATP that we used, leaving us with a net of 0 ATP molecules up to this stage of glycolysis.Again, we see that an atom of magnesium is involved to shield the negative charges on the phosphate groups of the ATP molecule.

Reaction 8: IsomerizationThis step involves a simple rearrangement of the position of the phosphate group on the 3 phosphoglycerate molecule, making it 2 phosphoglycerate. The molecule responsible for catalyzing this reaction is called phosphoglycerate mutase (PGM). A mutase is an enzyme that catalyzes the transfer of a functional group from one position on a molecule to another.The reaction mechanism proceeds by first adding an additional phosphate group to the 2′ position of the 3 phosphoglycerate. The enzyme then removes the phosphate from the 3′ position leaving just the 2′ phosphate, and thus yielding 2 phsophoglycerate. In this way, the enzyme is also restored to its original, phosphorylated state.

Reaction 9: DehydrationEach of the phosphoglycerate molecules undergoes dehydration (loss of water) by the enzyme enolase. Enolase works by removing a water group, or dehydrating the 2 phosphoglycerate. The specificity of the enzyme pocket allows for the reaction to occur through a series of steps too complicated to cover here.

Reaction 10: Phosphate TransferThe final step of glycolysis converts phosphoenolpyruvate into pyruvate with the help of the enzyme pyruvate kinase. As the enzyme’s name suggests, this reaction involves the transfer of a phosphate group. The phosphate group attached to the 2′ carbon of the PEP is transferred to a molecule of ADP, yielding ATP. Again, since there are two molecules of PEP, here we actually generate 2 ATP molecules.

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