• Krebs
  • Our results delineate a novel fumarate-dependent pathway in the regulation of HPH activity and highlight a previously unrecognized relationship between dysregulated Krebs cycle metabolic intermediates and HIF expression. (aacrjournals.org)
  • FH inactivation and subsequent blockade of the Krebs cycle, coupled with fumarate-mediated HIF upregulation, will likely drive the selection for cells undergoing increased glycolysis, thereby creating an environment permissive for tumorigenesis. (aacrjournals.org)
  • The mitochondrial isoenzyme is involved in the Krebs Cycle (also known as the Tricarboxylic Acid Cycle [TCA] or the Citric Acid Cycle), and the cytosolic isoenzyme is involved in the metabolism of amino acids and fumarate. (wikipedia.org)
  • catalyzes
  • Arginosuccinase, EC 4.3.2.1 (argininosuccinate lyase), which catalyzes the formation of arginine and fumarate from argininosuccinate, the last step in the biosynthesis of arginine. (wikipedia.org)
  • Adenylosuccinase, EC 4.3.2.2 (adenylosuccinate lyase), which catalyzes the eighth step in the de novo biosynthesis of purines, the formation of 5'-phosphoribosyl-5-amino-4-imidazolecarboxamide and fumarate from 1-(5- phosphoribosyl)-4-(N-succino-carboxamide). (wikipedia.org)
  • enzymes
  • A number of enzymes, belonging to the lyase class, for which fumarate is a substrate, have been shown to share a short conserved sequence around a methionine which is probably involved in the catalytic activity of this type of enzymes. (wikipedia.org)
  • activity
  • Furthermore, we provide direct evidence that fumarate inhibits HPH activity by competing with HPH's co-substrate 2-oxoglutarate, thus preventing VHL recognition of HIF. (aacrjournals.org)
  • The diagnosis is made either by testing of the fumarate hydratase activity in cultured skin fibroblasts or lymphoblastoid cells and demonstrating reduced activity (≤60%) or by molecular genetic testing. (wikipedia.org)