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Biological Chemistry Topics                                                                                  

Glycolysis


temporary graphicGlucose to Fructose

The first step in the preparatory phase of glycolysis is the phosphorylation of glucose catalyzed by hexokinase. Glucose is phosphorylated at the sixth carbon by transfer of the terminal phosphoryl group from ATP, yielding glucose 6-phosphate.

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This reaction is irreversible under intracellular conditions. Hexokinase is present in all cells of all organisms and has been broadly studied. Multiple forms or isozymes (different proteins catalyzing the same reaction) occur in both yeast and mammals. Four isozymes have been isolated form mammalian tissue. All catalyze the same reaction but have different Km values for glucose. Hexokinase I,II and III are found in muscle and have Km ~ 1x10-6 to 1x10-4. Hexokinase IV, aka glucokinase is found  in liver and has a lower affinity for glucose, Km = 1x10-2, than muscle hexokinase. Muscle consumes glucose for energy, while the liver produces and distributes glucose for other tissues.

The second step in the preparatory stage of glycolysis is the reversible conversion of glucose 6-phosphate, an aldose, into fructose 6-phosphate, a ketose, by catalysis of glucose 6- phosphate isomerase.

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Advance Topic: Glycolysis - Glucose Phosphorylation (Biochemistry)


Cleavage of Fructose

The third step in the preparatory phase of glycolysis is the phosphorylation of fructose 6-phosphate. Phosphofructokinase 1 (PFK-1) catalyzes the transfer of a phosphoryl group from ATP to the first carbon of fructose 6-phosphate, loosing a hydroxyl to yield fructose 1,6-bisphosphate.

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This reaction is irreversible under intracellular conditions and a critical regulatory step of glycolysis. This is the first committed step of glycolysis because some substrates may bypass the hexokinase step and glucose 6-phosphate can enter other pathways rather than continue glycolysis.

PFK-1 is a major regulatory point for glycolysis. Its activity increases when the ATP supply is depleted, signaled by an excess ADP or AMP. It is inhibited by excess ATP.

PFK-1 has the suffix "1" because there is a PFK-2 that catalyses the synthesis of fructose 2,6-bisphosphate. Some bacteria, protists and all plants have PFK that does not use ATP but pyrophosphate.

The fourth step in the preparatory phase of glycolysis is the cleavage of fructose 1,6-bisphosphate by aldolase into dehydroxyacetone phosphate and glyceraldehyde 3-phosphate.

At this point, two triose phosphates are present, but only glyceraldehyde 3- phosphate is a substrate for later reactions. Thus the last step of the preparatory phase of glycolysis is the interconversion of the triose phosphate, catalyzed by triose phosphate isomerase.

The reaction catalyzed by aldolase can proceed readily in either direction and is not a major control point in glycolysis. Products are removed quickly by the next two steps, pulling the reaction in the direction of cleavage.

The reaction catalyzed by triose phosphate isomerase is near equilibrium, but products are removed quickly by the next reaction. Because of this enzyme, two molecules of glyceraldehyde 3-phosphate are supplied by glycolysis per molecule of glucose.

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Advance Topic: Glycolysis - Fructose Phosphates (Biochemistry)


Oxidation of Glyceraldehyde

The sixth step of glycolysis (first step of the payoff phase) is the oxidation and phosphorilation of glyceraldehyde 3-phosphate to 1,3 bisphosphoglycerate. The recovery of energy from the triose phosphate beguins with this reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase. A molecule of NAD+ is reduced to NADH.

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The anhydride bond formed using inorganic phosphate has a very high standard free energy of hydrolysis to be used in the next step. Steps 6 to 7 couple the oxidation of an aldehyde to a carboxylic acid with the phosphorylation of ADP to form ATP.

The seventh step of glycolysis is the phosphoryl transfer frm 1,3 bisphosphoglyceate to ADP catalyzed by phosphoglycerate kinase. This reaction generates ATP and 3-phosphoglycerate.

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This is the first ATP generating step of glycolysis, yet it is a near equilibrium reaction in cells, and not a regulatory step.

The formation of ATP by transfer of a phosphoryl group froms a high energy compound to ADP is a substrate-level phosphorylation. Such a phosphorylation involves soluble enzymes and chemical intermediaries. That is different from respiratory phosphorylation, which involves membrane-bound enzymes and transmembrane gradients of protons.

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Advance Topic: Glycolysis - Glucose Phosphorylation (Biochemistry)


Generation of Pyruvate

The eigth step of glycolysis is the conversion of 3-phosphoglycerate to 2-phosphoglycerate by phosphoglycerate mutase in a near equilibrium reaction.

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Mutases are isomerases that catalyze the transfer of functional groups, in thiscase a phosphoryl, from one part of the molecule to another.

The ninth step of glycolysis is the dehydration of 2-phosphoglycerateto phosphoenol pyruvate (PEP. Catalyzed by enolase, thisreaction removes a water molecule in a near equilibrium reaction. PEP is a much higher energy compound than 2-phosphoglycerate.

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The last step of glycolysis is the transfer of the phophoryl group from PEP to ADP. This second substrate-level phosphorylation of glycolysis is catalyzed by pyruvate kinase. It is metabolically irreversible and another site of regulation by allosteric modulators and covalent modifications.

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Advance Topic: Glycolysis - Glucose Phosphorylation (Biochemistry)


Regulation of Glycolysis

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Other Sugars in Glycolysis

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Anaerobic Pyruvate Metabolism

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Aerobic Pyruvate Metabolism

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Continue to "Pyruvate" or take a test: [T1] [T2] [T3].

Need more practice? Answer the following review questions:

1- Describe and draw the first step in the preparatory phase of glycolysis, including all reactants and products, and indicate the enzyme.

2- What is an isozyme?

3- List the hexokinase isozymes and describe their properties.

4- What is the difference between muscle and liver in their use of glucose?

5- Describe and draw the second step in the preparatory phase of glycolysis, including all reactants and products, and indicate the enzyme.

6- Describe and draw the third step in the preparatory phase of glycolysis, including all reactants and products, and indicate the enzyme.

7- Why is the step catalyzed by PFK-1 the first committed step of glycolysis?

8- Which reaction is a major regulatory step of glycolysis and how is it regulated?.

9- What is the difference in the PFK-1 reaction between animals, bacteria, protists and plants?

10- Describe and draw the fourth step in the preparatory phase of glycolysis, including all reactants and products, and indicate the enzyme.

11- Describe the fifth step of the preparatory phase of glycolysis, including all reactants and products, and indicate the enzyme.

12- How many molecules of glyceraldehyde are obtained from one molecule of glucose?

13- Describe and draw the sixth step of glycolysis, including all reactants and products, and indicate the enzyme.

14- How is energy recovered in the formation of 1,3-bisphosphoglycerate?

15- What is the importance of the bond formed in the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase?

16- Describe and draw the seventh step of glycolysis, including all reactants and products, and indicate the enzyme.

17- How is energy recovered in the formation of 3-phosphoglycerate?

18- What is a substrate level phosphorylation?

19- Describe and draw the eight step of glycolysis, including all reactants and products, and indicate the enzyme.

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22- Describe and draw the ninth step of glycolysis, including all reactants and products, and indicate the enzyme.

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25- Describe and draw the ninth step of glycolysis, including all reactants and products, and indicate the enzyme.