fumarase (fumarate hydratase mitochondrial, FH)

Function

• catalyzes conversion of fumarate to malate
• carbohydrate metabolism, tricarboxylic acid cycle
• acts as a tumor suppressor

(S)-malate <--> fumarate + H2O

Structure

• homotetramer
• belongs to the class-II fumarase/aspartase family, fumarase subfamily
• initiator Met-1 is removed
• contains a N-acetylalanine at position 2
• isoform cytoplasmic is acetylated at position 2
• 2 substrate binding sites:
  • catalytic A site
  • non-catalytic B site may play a role in transfer of substrate or product between active site & solvent; alternatively, the B site may bind allosteric effectors

Compartment

mitochondria, cytoplasm

Alternative initiation

named isoforms=2

Pathology

• defects in FH are the cause of fumarase deficiency
• defects in FH are the cause of multiple cutaneous & uterine leiomyomata
• defects in FH are the cause of hereditary leiomyomatosis & renal cell cancer

More general terms

• hydro-lyase, hydratase or dehydratase
• citric acid cycle enzyme

Additional terms

• citric acid cycle, Krebs cycle or tricarboxylic acid [TCA] cycle

Database

• OMIM: https://mirror.omim.org/entry/136850
• OMIM: https://mirror.omim.org/entry/150800
• OMIM: https://mirror.omim.org/entry/605839
• OMIM: https://mirror.omim.org/entry/606812
• UniProt: http://www.uniprot.org/uniprot/P07954.html