Disease relevance of glutaconyl-CoA

• Here we present the crystal structure of the decarboxylase subunit (Gcdalpha) from Acidaminococcus fermentans and its complex with glutaconyl-CoA [1].
• [2'-13C]Biotin was incorporated into avidin (egg white), glutaconyl-CoA decarboxylase (EC 4.1.1.70) from Acidaminococcus fermentans and the biotin carrier of transcarboxylase from Propionibacterium freudenreichii (EC 2.1.3.1) [2].
• The subunits are very similar to those of the glutaconyl-CoA decarboxylases from the gram-positive bacteria [3].
• Purification, characterisation and reconstitution of glutaconyl-CoA decarboxylase, a biotin-dependent sodium pump from anaerobic bacteria [4].
• The glutaconyl-CoA decarboxylases from the gram-positive bacteria Acidaminococcus fermentans and Clostridium symbiosum have a lower apparent Km for Na+ (1 mM) and were not stimulated by phospholipids [3].

High impact information on glutaconyl-CoA

• The active sites of the dimeric Gcdalpha lie at the two interfaces between the mono mers, whereas the N-terminal domain provides the glutaconyl-CoA-binding site and the C-terminal domain binds the biotinyllysine moiety [1].
• Glutaconyl-CoA decarboxylase from Acidaminococcus fermentans (clostridal cluster IX), a strict anaerobic inhabitant of animal intestines, uses the free energy of decarboxylation (delta G(o) approximately -30 kJ mol-1) in order to translocate Na+ from the inside through the cytoplasmic membrane [5].
• The largest subunit, alpha or GcdA (65 kDa), catalyses the transfer of CO2 from glutaconyl-CoA to biotin covalently attached to the gamma-subunit, GcdC [5].
• The sodium ion translocating glutaconyl-CoA decarboxylase from Acidaminococcus fermentans: cloning and function of the genes forming a second operon [5].
• Earlier observations of a second, lower affinity binding site for Na+ of glutaconyl-CoA decarboxylase (apparent K(m) 30 mM) were confirmed by identification of the cysteine residue 243 of GcdB between the putative hellces VII and VIII, which could be specifically protected from alkylation by Na+ [5].

Chemical compound and disease context of glutaconyl-CoA

• 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans catalyzes the chemical difficult elimination of water from (R)-2-hydroxyglutaryl-CoA to glutaconyl-CoA [6].
• A biotin-dependent sodium pump: glutaconyl-CoA decarboxylase from Acidaminococcus fermentans [7].
• The steric course of the decarboxylation of glutaconyl-CoA to crotonyl-CoA, catalysed by the biotin-dependent sodium pump glutaconyl-CoA decarboxylase from Acidaminococcus fermentans, was elucidated using the sequence: chiral acetate----citrate----glutamate----glutaconyl-CoA----crotonyl-CoA ----chiral acetate [8].
• The other pathway via 2-hydroxyglutarate in Acidaminococcus fermentans and Fusobacterium nucleatum involves glutaconyl-CoA decarboxylase, which uses the free energy of decarboxylation to generate also an electrochemical Na(+) gradient [9].

Biological context of glutaconyl-CoA

• The pent-2-enoyl-CoA thus formed can be further metabolized by the usual enzymes of beta-oxidation, and by the further metabolism of propionyl-CoA to tricarboxylic acid-cycle intermediates [10].

Anatomical context of glutaconyl-CoA

• Mutant liver mitochondria did not oxidize glutaryl-CoA to glutaconyl-CoA, indicating deficiency of glytaryl-CoA dehydrogenase [11].
• Using a fraction purified from liver peroxisomes, we demonstrate that products of the glutaryl-CoA oxidase reaction are glutaconyl-CoA and H2O2 [12].
• These data indicate that in the absence of its mitochondrial dehydrogenation, glutaryl-CoA is oxidized in peroxisomes to glutaconyl-CoA which is probably transferred to mitochondria where it is decarboxylated and further processed [12].

Associations of glutaconyl-CoA with other chemical compounds

• The key intermediate is (R)-2-hydroxyglutaryl-CoA, which is dehydrated to glutaconyl-CoA, followed by decarboxylation to crotonyl-CoA [13].

References