The Overall Pathway of Glycolysis

The Overall Pathway of Glycolysis

The first stage of glucose metabolism in organisms from bacteria to humans is called glycolysis, and it was the first biochemical pathway elucidated. In glycolysis, one molecule of glucose (a six-carbon compound) is converted to fructose-1,6-bisphosphate (also a six-carbon compound), which eventually gives rise to two molecules of pyruvate (a three-carbon compound) (Figure 17.1). The glycolytic pathway (also called the Embden–Meyerhoff pathway) involves many steps, including the reactions in which metabolites of glucose are oxidized. Each reaction in the pathway is catalyzed by an enzyme specific for that reaction. In each of two reactions in the pathway, one molecule of ATP is hydrolyzed for each molecule of glucose metabolized; the energy released in the hydrolysis of these two ATP molecules makes coupled endergonic reactions possible. In each of two other reactions, two molecules of ATP are produced by phosphorylation of ADP for each molecule of glucose, giving a total of four ATP molecules produced. A comparison of the number of ATP molecules used by hydrolysis (two) and the number produced (four) shows that there is a net gain of two ATP molecules for each molecule of glucose processed in glycolysis. Glycolysis plays a key role in the way organisms extract energy from nutrients.

What are the possible fates of pyruvate in glycolysis?

When pyruvate is formed, it can have one of several fates (Figure 17.1). In aerobic metabolism (in the presence of oxygen), pyruvate loses carbon dioxide. The remaining two carbon atoms become linked to coenzyme A as an acetyl group to form acetyl-CoA, which then enters the citric acid cycle. There are two fates for pyruvate in anaerobic metabolism (in the absence of oxygen). In organisms capable of alcoholic fermentation, pyruvate loses carbon dioxide, this time producing acetaldehyde, which, in turn, is reduced to produce ethanol. The more common fate of pyruvate in anaerobic metabolism is reduction to lactate, called anaerobic glycolysis to distinguish it from conversion of glucose to pyruvate, which is simply called glycolysis. Anaerobic metabolism is the only energy source in mammalian red blood cells, as well as in several species of bacteria, such as Lactobacillus in sour milk and Clostridium botulinum in tainted canned foods.

In all these reactions, the conversion of glucose to product is an oxida-tion reaction, requiring an accompanying reduction reaction in which NAD⁺ is converted to NADH, a point to which we shall return when we discuss the pathway in detail. The breakdown of glucose to pyruvate can be summarized as follows:

Glucose (Six carbon atoms) -> 2 Pyruvate (Three carbon atoms)

2ATP + 4ADP + 2P_i - > 2ADP + 4ATP (Phosphorylation)

Glucose + 2ADP + 2P_i - > 2 Pyruvate + 2ATP (Net reaction)

Figure 17.2 shows the reaction sequence with the names of the compounds.

What are the reactions of glycolysis?

Step 1.Phosphorylationof glucose to give glucose-6-phosphate (ATP is thesource of the phosphate group). (See Equation 17.1)

Glucose + ATP - > Glucose-6-phosphate + ADP

Step 2.Isomerizationof glucose-6-phosphate to give fructose-6-phosphate.(See Equation 17.2)

Glucose-6-phosphate - > Fructose-6-phosphate

Step 3.Phosphorylationof fructose-6-phosphate to give fructose-1,6-bisphosphate (ATP is the source of the phosphate group). (See Equation 17.3)

Fructose-6-phosphate + ATP - > Fructose-1,6-bisphosphate + ADP

Step 4.Cleavageof fructose-1,6-bisphosphate to give two 3-carbon fragments,glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. (See Equation 17.4)

Fructose 1,6-bisphosphate - > Glyceraldehyde-3-phosphate

+ Dihydroxyacetone phosphate

Step 5.Isomerizationof dihydroxyacetone phosphate to give glyceraldehyde-3-phosphate. (See Equation 17.5)

Dihydroxyacetone phosphate - > Glyceraldehyde-3-phosphate

Step 6.Oxidation(and phosphorylation) of glyceraldehyde-3-phosphate togive 1,3-bisphosphoglycerate. (See Equation 17.6)

Glyceraldehyde-3-phosphate + NAD⁺ + P_i - > NADH + 1,3-bisphosphoglycerate + H⁺

Step 7.Transfer of a phosphate groupfrom 1,3-bisphosphoglycerate to ADP(phosphorylation of ADP to ATP) to give 3-phosphoglycerate. (See Equation 17.7) 1,3-bisphosphoglycerate + ADP - > 3-Phosphoglycerate + ATP

Step 8.Isomerizationof 3-phosphoglycerate to give 2-phosphoglycerate. (See Equation 17.8)

3-Phosphoglycerate - > 2-Phosphoglycerate

Step 9.Dehydrationof 2-phosphoglycerate to give phosphoenolpyruvate.(See Equation 17.9) 2-Phosphoglycerate - > Phosphoenolpyruvate + H₂O

Step 10.Transfer of a phosphate groupfrom phosphoenolpyruvate to ADP(phosphorylation of ADP to ATP) to give pyruvate. (See Equation 17.10) Phosphoenolpyruvate + ADP - > Pyruvate + ATP

Note that only one of the 10 steps in this pathway involves an electron-transfer reaction. We shall now look at each of these reactions in detail.

Summary

In glycolysis, glucose is converted to pyruvate in a multistep pathway.

When pyruvate is formed, it can be converted to carbon dioxide and water in aerobic reactions. It can also be converted to lactate under anaerobic conditions or, in some organisms, to ethyl alcohol.

Glucose is converted to pyruvate in a series of 10 reactions, only one of which is an oxidation.