Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Structural analogs of the substrate oxalacetate were examined as potential substrates and inhibitors for chicken liver mitochondrial phosphoenolpyruvate (P-enolpyruvate) carboxykinase. Steady-state kinetics were employed to characterize the inhibitory effects of these substrate analogs with the enzyme. Assays were carried out in both carboxylation and decarboxylation reaction directions. Pyruvate, beta-hydroxypyruvate, beta-mercaptopyruvate, beta-fluoropyruvate, DL-lactate, glycolate, glycoaldehyde, glyoxylate, glyphosate, and DL-aspartate showed no inhibitory effects by steady-state kinetics. Oxalate, acetopyruvate, and DL-, D-, and L-glycerate exhibited weak noncompetitive inhibition of the P-enolpyruvate carboxykinase-catalyzed reaction. DL-3-Nitro-2-hydroxypropionic acid, 3-nitro-2-oxopropionic acid, DL-malate, malonate, tartronate, and alpha-ketobutyrate all show weak inhibition with estimated inhibition constants greater than 20 nM. Several of these compounds were investigated by 31P NMR to determine if they function as phosphoryl acceptors for GTP. None of the compounds tested act as phosphoryl acceptors in the enzyme-catalyzed reaction. Chicken liver mitochondrial phosphoenolpyruvate carboxykinase shows a remarkably high degree of specificity at the binding site of oxalacetate.
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PMID:Analogs of oxalacetate as potential substrates for phosphoenolpyruvate carboxykinase. 232 53

The interactions of the substrate phosphoenolpyruvate and the substrate analogues (Z)-phosphoenol-alpha-ketobutyrate and (E)-phosphoenol-alpha-ketobutyrate with the enzyme-Mn complex of chicken liver phosphoenolpyruvate carboxykinase have been investigated by 1H and by 31P nuclear relaxation rate studies. Studies of the 1H and the 31P relaxation rates of the ligands in the binary Mn-ligand complexes show that these ligands interact with the metal ion via the phosphate group but not through the carboxylate. An inner sphere coordination complex is formed but the metal-ligand complex is not in the most extended conformation. In the relaxation rate studies of the ligands in the presence of the enzyme, conditions were adjusted so that all of the Mn2+ that was added resided in the ternary enzyme-Mn-ligand complex. The 1H relaxation rates for each of the three ligands were measured at 100 and at 300 MHz. In each case the normalized paramagnetic effects showed that 1/(pT2p) was greater than 1/(pT1p). A frequency dependence of the 1/(pT1p) and 1/(pT2p) values was also measured. The correlation time, tau c, for the Mn-1H interaction was calculated from the frequency dependence of 1/(pT1p) assuming a maximal frequency dependence of tau c and assuming no frequency dependence of tau c and from the T1M/T2M ratios at each frequency. The tau c values for all of the complexes, calculated at 100 MHz, varied from approximately 0.3 to 2.0 ns. These values were used to calculate the Mn-1H distances in each of the ternary complexes. The relaxation rates of 31P were also measured.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:1H and 31P relaxation rate studies of the interaction of phosphoenolpyruvate and its analogues with avian phosphoenolpyruvate carboxykinase. 409 95