Glycolysis Flashcards

Flashcards on Glycolysis and its Regulation

Glucose

Monosaccharide, 6-carbon molecule, end-product of digestive breakdown of carbohydrates, water-soluble solute that can be transported through the cell membrane.

GLUT Transporters for glucose across membrane

Different GLUT Transporters in the body that are insulin-independent, except GLUT IV which is insulin-dependent

Glycolysis

Employed by all tissues in which glucose is broken down to provide energy (in the form of ATP) and intermediates for other metabolic pathways.

Pyruvate

End-product of oxidation of glucose in aerobic cells is pyruvate (3-carbon molecule).

Energy Investment Phase

Phosphorylated forms of intermediates are synthesized at the expense of ATP

Energy Generation Phase

A net of two molecules of ATP are formed by substrate-level phosphorylation per glucose metabolized.

Substrate-level phosphorylation

Energy needed for the production a high-energy phosphate (e.g. phosphate in ATP) comes from a substrate rather than from the electron transport chain

Phosphorylated glucose

There are no specific transmembrane carriers for phosphorylated glucose, hence they do not readily penetrate the cell membrane

Glucose 6-phosphate (G6P)

Irreversible phosphorylation of glucose effectively trapping the sugar as cytosolic glucose 6-phosphate (G6P).

Hexokinase

Catalyzes the phosphorylation of glucose, with different isozymes having varying properties.

Hexokinase I, II, III

Most tissues; low Km (high affinity for glucose); Low Vmax; inhibited by G6P.

Hexokinase IV (Glucokinase)

Liver parenchymal cells and beta cells of the pancreas; High Km (low affinity for glucose); High Vmax; induced by insulin.

Phosphohexose Isomerase

Isomerization of glucose 6-phosphate (G6P) to fructose 6-phosphate (F6P).

Phosphofructokinase-1 (PFK-1)

Most important control point and the rate-limiting step and committed step of glycolysis. Irreversible phosphorylation of carbon 1 producing fructose 1,6-bisphosphate (F1,6-BP).

Aldolase

Aldolase cleaves fructose 1,6-bisphosphate (F1,6-BP) to dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P).

Triose phosphate isomerase

Triose phosphate isomerase interconverts dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.

Glyceraldehyde 3-phosphate dehydrogenase

Conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate (1,3-BPG) by glyceraldehyde 3-phosphate dehydrogenase.

Phosphoglycerate kinase

Conversion of 1,3-BPG to 3-phosphoglycerate (3-PG) catalyzed by phosphoglycerate kinase; produces ATP.

Phosphoglycerate mutase

Shift of phosphate group from carbon 3 to carbon 2 of phosphoglycerate by phosphoglycerate mutase; freely reversible step.

Enolase

Dehydration of 2-phosphoglycerate (2-PG) by enolase, results in the formation of phosphoenolpyruvate (PEP), reversible step.

Pyruvate kinase

Conversion of PEP to pyruvate catalyzed by pyruvate kinase; Equilibrium of the reaction favors ATP formation; third irreversible reaction of glycolysis.

Aerobic Conditions

Conversion of pyruvate to Acetyl-CoA, a major fuel in TCA (or citric acid) cycle, under cells adequate oxygen supply

Anaerobic Conditions

Conversion of pyruvate to lactate catalyzed by lactate dehydrogenase under scarcity in oxygen supply.

Oxidative Phosphorylation

ATP generation as a result from the transfer of electrons from NADH and FADH2 to oxygen by a series of electron carriers

Allosteric Regulation

Enzyme has an overall three-dimensional shape with an active site and an allosteric site. Enzyme can either be allosterically activated or inhibited.

Hormonal Regulation

Covalent modification of regulatory enzymes through phosphorylation / dephosphorylation. Seen in insulin and glucagon

Glucose (as a glucokinase activator)

Brings glucokinase out of the liver allowing it to stimulate the phosphorylation of glucose to G6P

Glucose-6-phosphate (as a glucokinase inhibitor)

Puts glucokinase back into the nucleus

Insulin

Released from pancreatic beta cells when glucose levels are high; activates hexokinase and glucokinase

Glucagon

Released from the pancreatic alpha cells when glucose levels are low; inhibits hexokinase and glucokinase

Fructose 2,6-bisphosphate

Most powerful regulator of PFK-1.

Feed forward reaction

Metabolite produced early in the pathway activates an enzyme that catalyze a reaction further down the pathway.

1. Glucose

Monosaccharide, 6-carbon molecule, end-product of digestive breakdown of carbohydrates, water-soluble solute that can be transported through the cell membrane.

2. GLUT Transporters

Different GLUT Transporters in the body that are insulin-independent, except GLUT IV which is insulin-dependent

3. Glycolysis

Employed by all tissues in which glucose is broken down to provide energy (in the form of ATP) and intermediates for other metabolic pathways.

4. Pyruvate

End-product of oxidation of glucose in aerobic cells is pyruvate (3-carbon molecule).

5. Energy Investment Phase

Phosphorylated forms of intermediates are synthesized at the expense of ATP

6. Energy Generation Phase

A net of two molecules of ATP are formed by substrate-level phosphorylation per glucose metabolized.

7. Substrate-level phosphorylation

Energy needed for the production a high-energy phosphate (e.g. phosphate in ATP) comes from a substrate rather than from the electron transport chain

8. Phosphorylated glucose

There are no specific transmembrane carriers for phosphorylated glucose, hence they do not readily penetrate the cell membrane

9. Glucose 6-phosphate (G6P)

Irreversible phosphorylation of glucose effectively trapping the sugar as cytosolic glucose 6-phosphate (G6P).

10. Hexokinase

Catalyzes the phosphorylation of glucose, with different isozymes having varying properties.

11. Hexokinase I, II, III

Most tissues; low Km (high affinity for glucose); Low Vmax; inhibited by G6P.

12. Hexokinase IV (Glucokinase)

Liver parenchymal cells and beta cells of the pancreas; High Km (low affinity for glucose); High Vmax; induced by insulin.

13. Phosphohexose Isomerase

Isomerization of glucose 6-phosphate (G6P) to fructose 6-phosphate (F6P).

14. Phosphofructokinase-1 (PFK-1)

Most important control point and the rate-limiting step and committed step of glycolysis. Irreversible phosphorylation of carbon 1 producing fructose 1,6-bisphosphate (F1,6-BP).

15. Aldolase

Aldolase cleaves fructose 1,6-bisphosphate (F1,6-BP) to dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P).

16. Triose phosphate isomerase

Triose phosphate isomerase interconverts dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.

17. Glyceraldehyde 3-phosphate dehydrogenase

Conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate (1,3-BPG) by glyceraldehyde 3-phosphate dehydrogenase.

18. Phosphoglycerate kinase

Conversion of 1,3-BPG to 3-phosphoglycerate (3-PG) catalyzed by phosphoglycerate kinase; produces ATP.

19. Phosphoglycerate mutase

Shift of phosphate group from carbon 3 to carbon 2 of phosphoglycerate by phosphoglycerate mutase; freely reversible step.

20. Enolase

Dehydration of 2-phosphoglycerate (2-PG) by enolase, results in the formation of phosphoenolpyruvate (PEP), reversible step.

21. Pyruvate kinase

Conversion of PEP to pyruvate catalyzed by pyruvate kinase; Equilibrium of the reaction favors ATP formation; third irreversible reaction of glycolysis.

22. Aerobic Conditions

Conversion of pyruvate to Acetyl-CoA, a major fuel in TCA (or citric acid) cycle, under cells adequate oxygen supply

23. Anaerobic Conditions

Conversion of pyruvate to lactate catalyzed by lactate dehydrogenase under scarcity in oxygen supply.

24. Oxidative Phosphorylation

ATP generation as a result from the transfer of electrons from NADH and FADH2 to oxygen by a series of electron carriers

25. Allosteric Regulation

Enzyme has an overall three-dimensional shape with an active site and an allosteric site. Enzyme can either be allosterically activated or inhibited.

26. Hormonal Regulation

Covalent modification of regulatory enzymes through phosphorylation / dephosphorylation. Seen in insulin and glucagon

27. Glucose (as a glucokinase activator)

Brings glucokinase out of the liver allowing it to stimulate the phosphorylation of glucose to G6P

28. Glucose-6-phosphate (as a glucokinase inhibitor)

Puts glucokinase back into the nucleus

29. Insulin

Released from pancreatic beta cells when glucose levels are high; activates hexokinase and glucokinase

Released