What kind of enzyme is fumarase?
TCA cycle enzyme
Fumarase is a TCA cycle enzyme which catalyzes the conversion of fumarate to L-malate in the mitochondria. Upon DNA damage the cytosolic echoform of fumarase is localized to the nucleus, there, its enzymatic activity catalyzes the reverse conversion of malate to fumarate, so causing local accumulation of fumarate.
What is the substrate of fumarase?
The main substrates for fumarase are malate and fumarate. However, the enzyme can also catalyze the dehydration of D-tartrate which results in enol-oxaloacetate. Enol-oxaloacetate can then izomerize into keto-oxaloacetate.
What reaction is catalyzed by fumarase?
reversible hydration of fumarate
The enzyme fumarase catalyzes the reversible hydration of fumarate to malate. The reaction catalyzed by fumarase is critical for cellular energetics as a part of the tricarboxylic acid cycle, which produces reducing equivalents to drive oxidative ATP synthesis.
What organelle is affected by Fumarase deficiency?
Fumarase deficiency is caused by a mutation in the fumarate hydratase (FH) gene in humans, which encodes the enzyme that converts fumarate to malate in the mitochondria.
What is the function of fumarate?
Fumarate has been shown to act as a competitive inhibitor of members of the 2-oxoglutarate-dependent oxygenase superfamily including the histone demethylase enzymes (HDMs), TET proteins and hypoxia-inducible factor (HIF) hydroxylases, thus activating oncogenic HIF pathways.
What is the fumarate hydratase gene?
FH (Fumarate Hydratase) is a Protein Coding gene. Diseases associated with FH include Fumarase Deficiency and Hereditary Leiomyomatosis And Renal Cell Cancer. Among its related pathways are Pyruvate metabolism and Citric Acid (TCA) cycle and Glucose metabolism.
Is fumarate a metabolite?
Altogether, the results of those studies suggest fumarate as an alternative and potentially flexible carbon sink for photosynthate similar to starch and indicates fumarate as a highly important metabolite in the primary metabolism of Arabidopsis.
Is the enzyme fumarase a cytosolic or mitochondrial enzyme?
In eukaryotes, the enzyme fumarase (also called fumarate hydratase, FH, in higher eukaryotes) is known to participate in the TCA (tricarboxylic acid) cycle in the mitochondrial matrix. However, a common theme, conserved from yeast to humans, is the existence of a cytosolic isoenzyme of fumarase [2], [3].
How is fumarase involved in recognition and recovery from DNA damage?
Our results indicate that cytosolic fumarase is involved in recognition and recovery from DNA damage, mainly from DNA double-strand breaks (DSBs). This suggests a new link between fumarase deficiency and tumorigenesis, which is probably HIF independent.
Is the fumarase dual distribution conserved in eukaryotes?
This suggests a new link between fumarase deficiency and tumorigenesis, which is probably HIF independent. As referred to above, fumarase dual distribution between the cytosol and mitochondria is conserved in all eukaryotes studied, including yeast and humans.
What is the role of fumarase and fumaric acid?
Our findings suggest that fumarase and fumaric acid are critical elements of the DNA damage response, which underlies the tumor suppressor role of fumarase in human cells and which is most probably HIF independent.