Fumarase

An enzyme involved in the citric acid cycle

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Overview

Fumarase, also known as fumarate hydratase, is an enzyme that plays a crucial role in the citric acid cycle, which is a key metabolic pathway that provides energy in the form of adenosine triphosphate (ATP) through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. Fumarase catalyzes the reversible hydration of fumarate to malate.

Structure

Fumarase is a homotetrameric enzyme, meaning it is composed of four identical subunits. Each subunit contains an active site where the conversion of fumarate to malate occurs. The enzyme is highly conserved across different species, indicating its essential role in cellular metabolism.

Function

Fumarase functions in the mitochondria of eukaryotic cells, where it participates in the citric acid cycle. The reaction it catalyzes is:

Fumarate + H_O _ L-malate

This reaction is important for the continuation of the citric acid cycle, which ultimately leads to the production of ATP, the energy currency of the cell. In addition to its role in energy production, fumarase is also involved in the regulation of reactive oxygen species and apoptosis.

Clinical Significance

Mutations in the gene encoding fumarase can lead to a rare metabolic disorder known as fumarase deficiency. This condition is characterized by severe neurological impairment, developmental delay, and encephalopathy. Fumarase deficiency is inherited in an autosomal recessive pattern.

Fumarase has also been implicated in certain types of cancer, particularly hereditary leiomyomatosis and renal cell carcinoma (HLRCC). In these cases, loss of fumarase activity leads to the accumulation of fumarate, which can act as an oncometabolite, promoting tumorigenesis.

Biochemical Pathway

Diagram of the citric acid cycle, showing the position of fumarase.

Fumarase is a key enzyme in the citric acid cycle, which is depicted in the diagram. It catalyzes the conversion of fumarate to malate, which is then oxidized to oxaloacetate by malate dehydrogenase. This step is crucial for the regeneration of oxaloacetate, allowing the cycle to continue.

Research and Applications

Research into fumarase has provided insights into its role in cellular metabolism and its potential as a target for therapeutic intervention in metabolic disorders and cancer. Studies are ongoing to better understand the regulation of fumarase activity and its interactions with other metabolic pathways.

Related pages

• Citric acid cycle
• Fumarate
• Malate
• Mitochondria
• Metabolic pathway