Disease relevance of pyridoxal phosphate

• The hdc genes encoding the inducible pyridoxal-P-dependent histidine decarboxylase (HisDCase) of Klebsiella planticola and Enterobacter aerogenes were isolated, sequenced, and expressed in Escherichia coli under control of the lac promoter, and the overproduced enzymes were purified to homogeneity from the recombinant host [1].
• Chemical modification of the Anabaena wild-type enzyme with pyridoxal-P indicated that Lys419 was the only lysyl residue modified [2].
• These closely related pyridoxal-P enzymes show no sequence homology with the pyruvoyl-dependent HisDCases of Gram-positive bacteria [1].
• PA:PL was not affected by wide variations in vitamin B-6 intake or by the wide range of pyridoxal-P concentrations encountered while screening for hypophosphatasia [3].
• The results suggest that pyridoxal-5-phosphate or structural analogs may ultimately be useful in reducing the incidence of dental caries [4].

High impact information on pyridoxal phosphate

• SOS4 encodes a pyridoxal kinase that is involved in the biosynthesis of pyridoxal-5-phosphate, an active form of vitamin B6 [5].
• We propose that pyridoxal-5-phosphate regulates Na(+) and K(+) homeostasis by modulating the activities of ion transporters [5].
• Serine racemase is a protein representing an additional family of pyridoxal-5' phosphate-dependent enzymes in eukaryotes [6].
• The fluorescence of this intermediate is used to characterize the binding sites for the cofactor (pyridoxal-P) and substrates, which are shown to exist on the nicked protein [7].
• FANFT pretreatment decreased alanine aminotransferase activities in rats in some groups and the feeding of tryptophan had variable effects on alanine aminotransferase and plasma pyridoxyl phosphate levels [8].

Chemical compound and disease context of pyridoxal phosphate

• On the basis of the above results and taking into account the reported concentrations of fructose-P2, of pyridoxal-P, and of the adenine nucleotide pool and its energy charge in E. coli strains, it is concluded that furctose-P2 is the important physiological allosteric activator of E. coli ADP-glucose pyrophosphorylase [9].
• Biosynthesis of bacterial glycogen. Isolation and characterization of the pyridoxal-P allosteric activator site and the ADP-glucose-protected pyridoxal-P binding site of Escherichia coli B ADP-glucose synthase [10].
• Static absorbance measurements of D-serine dehydratase from Escherichia coli taken at 2 degrees C show that during the steady-state course of D-serine conversion the absorption maximum of the Schiff base of the cofactor pyridoxal 5'-phosphate (pyridoxal-P) is shifted from 415 to 442 nm [11].
• Changes in the active site of Escherichia coli maltodextrin phosphorylase created by substituting residues Lys533, Arg534, Tyr538, and Glu637 were monitored in the absence and presence of arsenate as substrate analogue using pyridoxal-P as 31P NMR reporter [12].
• Nine adult rats underwent occlusion of the left coronary artery (LCA) to assess the ability of a manganese chelate of N, N'-Bis (pyridoxal-5-phosphate) ethylenediamine-N, N'-diacetic acid (Mn-DPDP), to delineate acute myocardial ischemia [13].

Biological context of pyridoxal phosphate

• It is also shown that, when dimeric apotryptophanase is incubated in the presence of its cofactor and substrate, the kinetics of appearance of active molecules is of second order in enzyme and is independent of the pyridoxal-P concentration; its rate constant has been determined (5-10(4) M-1 S-1) [14].
• The ratio of specific activities for pyridoxal-P and p-nitrophenyl-P hydrolysis remains relatively constant during the isolation of plasma membranes [15].
• No homology was found in either the amino acid sequence of the pyridoxal-P binding peptide or the amino-terminal amino acid sequence between the enzyme and other pyridoxal-P-dependent enzymes [16].
• The experimental results have been formulated into a proposed reaction mechanism for deamination of amino acids by pyridoxal-P [17].
• It is concluded that the transport of pyridoxal-P into isolated rat liver mitochondria is energy-independent and is most consistent with passive diffusion facilitated by protein binding once this coenzyme enters the different compartments of the mitochondria [18].

Anatomical context of pyridoxal phosphate

• Human erythrocytes rapidly convert vitamin B6 to pyridoxal-P and contain soluble phosphatase activity which dephosphorylates pyridoxal-P at a pH optimum of 6-6 [19].
• These data indicate that pyridoxal-P can rapidly enter the intermembrane space of isolated mitochondria, but its penetration into the matrix occurs at a slower and more sustained rate (i.e. 9-16 pmol/h/mg of protein) [18].
• A nondialyzable inhibitor was apparently formed when intact microsomes were reacted with pyridoxal-P and NaBH4; this inhibition was also reversed by procedures which changed the kinetic properties of glucose-6-phosphatase [20].
• Pyridoxal-P is not hydrolyzed by the acid phosphatase of intact lysosomes [15].
• Additionally, as reflected by the lower specific radioactivity of [14C]pyridoxal-P in mitochondria than that in cytosol, the extent of mixing of newly synthesized and endogenous pools of pyridoxal-P in these subcellular compartments is heterogeneous [21].

Associations of pyridoxal phosphate with other chemical compounds

• The ratio of pyridoxal-P to pyridoxamine-P in isolated mitochondria is increased with 2-oxoglutarate as substrate and decreased with glutamate [21].
• In contrast, thrombin modified with pyridoxal-P in the presence of heparin incorporated up to 1 mol of pyridoxal-P per mol of thrombin [22].
• Among red blood cell vitamins, alpha-EGR was the only predictor of tHcy levels (P = 0.035), whereas alpha-ETK, red blood cell pyridoxal-5-phosphate supply (alpha-EGOT) and red blood cell folate levels had no effect [23].
• The P2 purinoceptor antagonists suramin, pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid, and pyridoxal-5-phosphate acted similarly at both receptor forms, producing noncompetitive inhibition, with IC50 values of 1-5 microM for suramin and pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid and 10-20 microM for pyridoxal-5-phosphate [24].
• Chronic administration of levodopa may result in an adaptive alteration in the decarboxylase system with an increased cellular ability to synthesize pyridoxal-5-phosphate from pyridoxine, possibly through enzyme induction [25].

Gene context of pyridoxal phosphate

• The inferred amino acid sequence of this clone shares 81% identity with the published Drosophila Ddc cDNA, including complete identity with twenty-four contiguous amino acids encompassing the pyridoxal-5-phosphate cofactor binding domain [26].
• Instead, PHOSPHO2 shows high specific activity toward pyridoxal-5-phosphate (V(max) of 633 nmol min(-1) mg(-1) and K(m) of 45.5 microM) [27].
• Two forms, termed GAD65 and GAD67, are the products of two genes and differ in sequence, molecular weight, interaction with the cofactor, pyridoxal 5'-phosphate (pyridoxal-P), and level of expression among brain regions [28].
• In the presence of formylhistidinol and formylhistidine (specific ligands of the enzyme) inactivation of histidinol dehydrogenase by pyridoxal-P is prevented [29].
• Profile analysis of kynureninase primary structure indicated the presence of a pyridoxal-P-binding site consensus sequence assigned to class-V aminotransferases, with Lys276 being the residue binding the cofactor [30].

Analytical, diagnostic and therapeutic context of pyridoxal phosphate

• Peptide mapping of tryptic digests indicated that two distinct peptides were specifically modified by pyridoxal-P [31].
• Significant decreases in plasma pyridoxal-5-phosphate (PLP), plasma glutamic-oxaloacetic transaminase (PGOT) and erythrocyte glutamic-oxaloacetic transaminase (EGOT) were found in 29 uremic patients including 14 who had been on hemodialysis an average of 15.8 months [32].
• Spectrophotometric titration of apoenzyme with pyridoxal-P showed 1 mol of pyridoxal-P bound per 52,000 g of enzyme [33].
• A sensitive and convenient method of endopeptidase assay using as substrate globin modified with pyridoxal-5-phosphate was used for determination of acid proteinases in bovine hypothalamus separated by isoelectric focusing [34].
• Preliminary evidence is presented that plasma pyridoxal-5-phosphate levels are considerably and significantly reduced (P less than 0.0001) in patients suffering from myocardial infarction when compared to a healthy control group [35].

References