Enolase

PDB 1pdz EBI

2XSX pdb

Enolase 2ONE wpmp

Enolase is an enzyme that plays a critical role in the glycolysis and gluconeogenesis pathways. It catalyzes the conversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP) and vice versa. This reaction is essential for the metabolic processes that provide energy to cells.

Structure

Enolase is a metalloenzyme that requires Mg²⁺ as a cofactor for its activity. It is a dimeric enzyme, meaning it consists of two subunits. Each subunit has a binding site for the substrate and the cofactor. The enzyme is highly conserved across different species, indicating its importance in cellular metabolism.

Function

In the glycolytic pathway, enolase catalyzes the penultimate step, converting 2-phosphoglycerate to phosphoenolpyruvate. This reaction is crucial for the subsequent production of ATP, the energy currency of the cell. In gluconeogenesis, the reverse reaction occurs, contributing to the synthesis of glucose from non-carbohydrate precursors.

Clinical significance

Enolase has been studied as a potential biomarker for various diseases. For example, neuron-specific enolase (NSE) is used as a marker for certain types of cancer, including neuroblastoma and small cell lung cancer. Elevated levels of NSE in the blood can indicate the presence of these malignancies.

Isoforms

There are three isoforms of enolase in humans: alpha, beta, and gamma. Each isoform is expressed in different tissues and has distinct physiological roles. Alpha-enolase is ubiquitous, beta-enolase is found primarily in muscle tissue, and gamma-enolase is predominantly expressed in neurons.

Regulation

The activity of enolase is regulated by various factors, including the availability of its substrate and cofactor, as well as by post-translational modifications. Phosphorylation and acetylation are known to affect enolase activity and stability.

Enolase gallery

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  Enolase with differentiated subunits

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  Enolase active site

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  Enolase mechanism2

See also

• Glycolysis
• Gluconeogenesis
• Metabolism
• Enzyme

Glucose

Hexokinase

ATP

ADP

Glucose 6-phosphate

Glucose-6-phosphate
isomerase

Fructose 6-phosphate

Phosphofructokinase-1

ATP

ADP

Fructose 1,6-bisphosphate

Fructose-bisphosphate
aldolase

Dihydroxyacetone phosphate

+

+

Glyceraldehyde 3-phosphate

Triosephosphate
isomerase

2 × Glyceraldehyde 3-phosphate

2 × 

Glyceraldehyde-3-phosphate
dehydrogenase

NAD⁺+ P_i

NADH + H⁺

NAD⁺+ P_i

NADH + H⁺

2 × 1,3-Bisphosphoglycerate

2 × 

Phosphoglycerate kinase

ADP

ATP

ADP

ATP

2 × 3-Phosphoglycerate

2 × 

Phosphoglycerate mutase

2 × 2-Phosphoglycerate

2 × 

Phosphopyruvate
hydratase (enolase)

 

H₂O

 

H₂O

2 × Phosphoenolpyruvate

2 × 

Pyruvate kinase

ADP

ATP

2 × Pyruvate

2 ×