Disease relevance of PCX

• The biochemistry of fatty liver and kidney syndrome. Biotin-mediated restoration of hepatic gluconeogenesis in vitro and its relationship to pyruvate carboxylase activity [1].
• Pyruvate carboxylase from Bacillus stearothermophilus: molecular size, biotin content and subunit constitution [2].

High impact information on PCX

• It does not contain biotin and its constituent polypeptides are smaller than those of pyruvate carboxylase [3].
• These tetramers, like pyruvate carboxylase, are very cold-labile and are protected from dissociation under these conditions by acetyl-CoA, a specific activator of this enzyme [3].
• Also, the structures form complexes with avidin and antibiotin antibody and thus, like pyruvate carboxylase, contain biotin [3].
• Initial velocity and isotope exchange studies confirmed that the over-all reaction, like that catalyzed by pyruvate carboxylase purified from rat liver and chicken liver, was a nonclassical Ping Pong Bi Bi Uni Uni sequence with ATP and HCO3-binding randomly in the Bi Bi partial reaction [4].
• Effects of Mg(2+) on the pre-steady-state kinetics of the biotin carboxylation reaction of pyruvate carboxylase [5].

Biological context of PCX

• The amino acid sequence of cPC shows approximately 77% identity to mammalian PC [6].
• Kinetics of nucleotide binding to pyruvate carboxylase [7].
• Incubation of affected slices in a biotin-containing nutrient medium restores both gluconeogenesis and pyruvate carboxylase actiivity (the latter to approx. 35% of the control valve) [1].
• VO2+(IV) complexes with pyruvate carboxylase: activation of oxaloacetate decarboxylation and EPR properties of enzyme-VO2+ complexes [8].
• Chicken liver pyruvate carboxylase catalyzes a nonclassical ping-pong mechanism in which the carboxylation of biotin at subsite 1 of the active site is coupled to the biotin-dependent carboxylation of pyruvate at subsite 2 [8].

Anatomical context of PCX

• Pyruvate carboxylase activities in red blood cells and liver of chicks and their dependency on biotin status. First results with activation assays. [9].
• With hepatocytes from biotin-deficient chicks, sensitivity to inhibition was increased, and was consistent with pyruvate carboxylase being rate-limiting [10].

Associations of PCX with chemical compounds

• Pyruvate carboxylase (PC) [EC 6.4.1.1] is a biotin-dependent carboxylase that catalyses the conversion of pyruvate to oxaloacetate [6].
• Binding of acetyl-CoA to chicken liver pyruvate carboxylase [11].
• Decarboxylation of oxalacetate by pyruvate carboxylase [12].
• Pyruvate carboxylase catalysis of phosphate transfer between carbamoyl phosphate and ADP [13].
• Isolation of a carboxyphosphate intermediate and the locus of acetyl-CoA action in the pyruvate carboxylase reaction [14].

Physical interactions of PCX

• Avidin is a slow-binding inhibitor of pyruvate carboxylase [15].

Regulatory relationships of PCX

• Avidin as a probe of the conformational changes induced in pyruvate carboxylase by acetyl-CoA and pyruvate [16].

Other interactions of PCX

• 2. Biotin deficiency decreased hepatic activity of pyruvate carboxylase [EC 6.4.1.1] but activity of acetyl-CoA carboxylase [EC 6.4.1.2] was comparatively unaffected [17].

Analytical, diagnostic and therapeutic context of PCX

• Molecular cloning and domain structure of chicken pyruvate carboxylase [6].
• Negatively stained enzyme-avidin complexes, seen at different stages of the titration of the biotin-binding sites on avidin with chicken liver pyruvate carboxylase, have been studied using electron microscopy [18].
• The determination of the availability to chicks of biotin in feed ingredients by a bioassay based on the response of blood pyruvate carboxylase (EC 6.4.1.1) activity [19].

References