GLYCOLYSIS

Submitted by

Dr. Sakshi Verma

Assistant Professor

Zoology Department

HMV, Jalandhar

• Glycolysis is the central pathway for glucose catabolism in which glucose (6-carbon compound) is converted into pyruvate (3-carbon compound) through a sequence of 10 steps.
• Glycolysis takes place in both aerobic and anaerobic organisms and is the first step toward the metabolism of glucose.
• The glycolytic sequence of reactions differs from one species to the other in the mechanism of its regulation and the subsequent metabolic fate of the pyruvate formed at the end of the process.
• In aerobic organisms, glycolysis is the prelude to the citric acid cycle and the electron transport chain, which together release most of the energy contained in glucose.
• It is also referred to as Embden-Meyerhof-Parnas or EMP pathway in honor of the pioneer workers in the field.
• Glycolysis occurs in the cell’s cytosol (cytoplasm).

• Glycolysis Equation
• A summary of the process of glycolysis cab be written as follows:

• During glycolysis, a single mole of 6-carbon glucose is broken down into two moles of 3-carbon pyruvate by a sequence of 10 enzyme-catalyzed sequential reactions. 

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The ten steps of glycolysis occur in the following sequence:

Step 1- Phosphorylation of glucose

In the first step of glycolysis, the glucose is initiated or primed for the subsequent steps by phosphorylation at the C₆ carbon.

The process involves the transfer of phosphate from the ATP to glucose forming Glucose-6-phosphate in the presence of the enzyme hexokinase and glucokinase (in animals and microbes).

This step is also accompanied by considerable loss of energy as heat.

Step 2- Isomerization of Glucose-6-phosphate:

Glucose 6-phosphate is reversibly isomerized to fructose 6-phosphate by the enzyme phosphohexoisomerase/phosphoglucoisomerase.

This reaction involves a shift of the carbonyl oxygen from C1 to C2, thus converting an aldose into a ketose.

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Step 3- Phosphorylation of fructose-6-phosphate:

This step is the second priming step of glycolysis, where fructose-6-phosphate is converted into fructose-1,6-bisphosphate in the presence of the enzyme phosphofructokinase.

Like in Step 1, the phosphate is transferred from ATP while some amount of energy is lost in the form of heat as well.

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Step 4- Cleavage of fructose 1, 6-diphosphate

This step involves the unique cleavage of the C-C bond in the fructose 1, 6-bisphosphate.

The enzyme fructose diphosphate aldolase catalyzes the cleavage of fructose 1,6-bisphosphate between C₃ and C₄ resulting in two different triose phosphates: glyceraldehyde 3-phosphate (an aldose) and dihydroxyacetone phosphate (a ketose).

The remaining steps in glycolysis involve three-carbon units, rather than six carbon units.

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Step 5- Isomerization of dihydroxyacetone phosphate

Glyceraldehyde 3-phosphate can be readily degraded in the subsequent steps of glycolysis, but dihydroxyacetone phosphate cannot be. Thus, it is isomerized into glyceraldehyde 3-phosphate instead.

In this step, dihydroxyacetone phosphate is isomerized into glyceraldehyde 3-phosphate in the presence of the enzyme triose phosphate isomerase.

This reaction completes the first phase of glycolysis.

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Step 6- Oxidative Phosphorylation of Glyceraldehyde 3-phosphate

Step 6 is one of the three energy-conserving or forming steps of glycolysis.

The glyceraldehyde 3-phosphate is converted into 1,3-bisphosphoglycerate by the enzyme glyceraldehyde 3-phosphate dehydrogenase (phosphoglyceraldehyde dehydrogenase).

In this process, NAD⁺ is reduced to coenzyme NADH by the H^– from glyceraldehydes 3-phosphate.

Since two moles of glyceraldehyde 3-phosphate are formed from one mole of glucose, two NADH are generated in this step.

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Step 7- Transfer of phosphate from 1, 3-diphosphoglycerate to ADP

This step is the ATP-generating step of glycolysis.

It involves the transfer of phosphate group from the 1, 3-bisphosphoglycerate to ADP by the enzyme phosphoglycerate kinase, thus producing ATP and 3-phosphoglycerate.

Since two moles of 1, 3-bisphosphoglycerate are formed from one mole of glucose, two ATPs are generated in this step.

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Step 8- Isomerization of 3-phosphoglycerate

The 3-phosphoglycerate is converted into 2-phosphoglycerate due to the shift of phosphoryl group from C3 to C2, by the enzyme phosphoglycerate mutase.

This is a reversible isomerization reaction.

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Step 9- Dehydration 2-phosphoglycerate

• In this step, the 2-phosphoglycerate is dehydrated by the action of enolase (phosphopyruvate hydratase) to phosphoenolpyruvate.
• This is also an irreversible reaction where two moles of water are lost.

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Step 10- Transfer of phosphate from phosphoenolpyruvate�This is the second energy-generating step of glycolysis.

Phosphoenolpyruvate is converted into an enol form of pyruvate by the enzyme pyruvate kinase.

The enol pyruvate, however, rearranges rapidly and non-enzymatically to yield the keto form of pyruvate (i.e. ketopyruvate). The keto form predominates at pH 7.0.

The enzyme catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate to ADP, thus forming ATP.

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• Fates of Pyruvate
• 1. First route: The pyruvate formed by glycolysis is further metabolized via one of three catabolic routes. In aerobic organisms or tissues, under aerobic conditions, glycolysis is only the first stage in the complete degradation of glucose (Fig. 14–3). Pyruvate is oxidized, with loss of its carboxyl group as CO2, to yield the acetyl group of acetyl-coenzyme A; the acetyl group is then oxidized completely to CO2 by the citric acid cycle. The electrons from these oxidations are passed to O2 through a chain of carriers in the mitochondrion, to form H2O. The energy from the electron-transfer reactions drives the synthesis of ATP in the mitochondrion.

• Fates of Pyruvate
• 2. The second route for pyruvate is its reduction to lactate via lactic acid fermentation. When vigorously contracting skeletal muscle must function under low oxygen conditions (hypoxia), NADH cannot be reoxidized to NAD, but NAD is required as an electron acceptor for the further oxidation of pyruvate. Under these conditions pyruvate is reduced to lactate, accepting electrons from NADH and thereby regenerating the NAD necessary for glycolysis to continue.

• Certain tissues and cell types (retina and erythrocytes, for example) convert glucose to lactate even under aerobic conditions, and lactate is also the product of glycolysis under anaerobic conditions in some microorganisms.
• 3. The third major route of pyruvate catabolism leads to ethanol. In some plant tissues and in certain invertebrates, protists, and microorganisms such as brewer’s yeast, pyruvate is converted under hypoxic or anaerobic conditions into ethanol and CO2, a process called ethanol (alcohol) fermentation

REFERENCES:

• Lehninger, A.L., Nelson, D.L. and Cox, M.M., 2005. Lehninger principles of biochemistry. Macmillan.
• Jain, J.L., 2004. Fundamentals of biochemistry. S. Chand Publishing.
• Satyanarayana, U., 2013. Biochemistry. Elsevier Health Sciences.