Summary 07032021

Aerobic glycolysis

References

Rodwell, V., Bender, D., Botham, K., Kennelly, P. & Weil, P. (2018). Harper Illustrated Biochemistry (31st ed.). McGraw Hill Education.

Li, X., Gu, J. & Zhou, Q. (2014). Review of aerobic glycolysis and its key enzymes – new targets for lung cancer therapy. Thoracic Cancer, 6, 17-24.

Biochemistry I

Paola Pimiento

This pathway converts glucose into pyruvate.

It is done in the presence of oxygen.

It happens in the cytoplasm.

Aerobic glycolysis has 10 steps:

Glycolysis is the main pathway for glucose and other carbohydrates.

It can be aerobic or anaerobic.

This pathway is preferred by tumor cells but instead of following the oxidation pathway in the mitochondria, these cells use the anaerobic mechanism of lactic acid fermentation.

This is called the Warburg effect.

When there is oxygen present and a mitochondria, the electron transport chain is the preferred pathway.

Pyruvate is decarboxylated by pyruvate dehydrogenase and turned into Acetyl CoA.

It can be used in the citric acid cycle.

This pathway is followed in anaerobic conditions or in cells that lack mitochondria.

Pyruvate is oxidated to lactate and NADH is turned to NAD+.

During this process NADH is produced, it is transported to participate in the electron transport chain.

Step 1

It enters the cell; it is phosphorylated by an enzyme to stay inside.

Hexokinase

Glucokinase

In most cells of the body except the liver and the beta cells in the pancreas.

It phosphorylates glucose in the liver and beta cells of the pancreas.

The result is glucose-6-phosphate.

This step is irreversible, and the product can inhibit the hexokinase activity.

This enzyme has high affinity for glucose.

This enzyme has lower affinity for glucose.

This enzyme must get rid of the glucose present in the hepatic porta system.

It regulates glucose levels in peripheric tissues.

Step 2

Glucose-6-phosphate

Glucose

It connects different metabolic pathways like glycolysis, gluconeogenesis, the pentose phosphate pathway and others.

Glucose-6-phosphate isomerase or phosphoglucoisomerase.

It isomerases the aldose into ketose.

The result is fructose-6-phosphate.

Step 3

Fructose-6-phosphate

Phosphofructokinase-1 (PFK1)

It phosphorylates the fructose-6-phosphate, its action is irreversible.

This enzyme can be induced, and it is regulated by allosteric inhibition.

It controls the speed at which glycolysis happens.

The result is fructose-1,6-bisphosphate.

Step 4

Fructose-1,6-bisphosphate

It splits the fructose-1,6-bisphosphate into two 3-carbon molecules.

Aldolase

Glyceraldehyde-3-phosphate (G3P)

Dihydroxyacetone phosphate

Phosphotriose isomerase

Glyceraldehyde-3-phosphate (G3P)

In this process there are many participants involved listed like this:

Substrates

Enzymes

Products

Step 6

Glyceraldehyde-3-phosphate (G3P)

Glyceraldehyde-3-phosphate dehydrogenase

It oxidates its substrate, it has 4 -SH groups that are derivates of cysteine. This enzyme needs NAD for its action.

A free -SH group is a byproduct of this action; it transfers the H to NAD+.

1,3-biphosphoglycerate

Step 7

1,6-biphosphoglycerate

Phosphoglycerate kinase

It uses ATP as a phosphate donor.

It transfers a phosphate group from the 1,6-biphosphoglycerate to an ADP.

ATP

3-phosphoglycerate

Because there are two triose molecules, in this step 2 ATPs are produced per glucose molecule.

Step 8

3-phosphoglycerate

It uses ATP as a phosphate donor.

Phosphoglycerate mutase

It isomerases 3-phosphoglycerate.

2-phosphoglycerate

Step 9

2-phosphoglycerate

Enolase

It can be inhibited by Fluorine.

It dehydrates the 2-phosphoglycerate molecule.

It depends on the presence of Mg and Mn ions.

Phosphoenolpyruvate

ATP

In this step 2 ATPs and 2 pyruvates are produced per glucose molecule.

Step 10

Phosphoenolpyruvate

Pyruvate kinase

It phosphorylates the substrate and transfers the phosphate group of phosphoenolpyruvate to an ADP molecule.

Pyruvate

This reaction is irreversible in physiological conditions.

Step 5

Regulation

Most of the steps in glycolysis can be reversible but there are some key steps that are irreversible, these regulate the rate at which this process is done.

Hexokinase

Phosphofructokinase 1

Pyruvate kinase

It is inhibited at normal concentrations of ATP in the cell.

This inhibition stops when there's presence of 5'AMP, it happens when ADP accumulates.

Because of this, gluconeogenesis needs different steps to bypass the irreversible steps.

Because there are two triose molecules, in this step, 2 NADH are produced per glucose molecule.

NADH