Disease relevance of PDXP

• Hypophosphatasia fibroblasts were markedly deficient (2%-5% control values) in alkaline and physiologic ALP activity when 4-MUP, PLP, and PEA were used as substrate [1].
• There was no significant difference in plasma PLP levels between those with liver disease due to alcohol and those with other varieties [2].
• Plasma levels of pyridoxal-5'-phosphate (PLP), the active coenzyme form of vitamin B6, were found to be significantly lower than normal in 22 out of 31 patients with decompensated cirrhosis or subacute hepatic necrosis [2].
• Because abnormalities in PLP metabolism have been shown to cause epileptic seizures in mice null for the TNAP gene, these kinetic data help explain the variable expressivity of epileptic seizures in hypophosphatasia patients [3].
• Obesity did not affect the plasma PLP levels in these black women [4].

Psychiatry related information on PDXP

• There was no difference in plasma PLP levels between the anxiety disorder groups and normal controls [5].
• One hundred and eighty-nine subjects with either generalized anxiety disorder, panic disorder, or obsessive-compulsive disorder were evaluated for plasma pyridoxal phosphate (PLP) levels and compared with normal controls [5].

High impact information on PDXP

• Defective metabolism of pyridoxal 5'-phosphate (PLP), characterized by elevated serum PLP levels, results in reduced levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain [6].
• CIN directly dephosphorylates cofilin with high specificity and colocalizes with cofilin in motile and dividing cells [7].
• Here we report the 3D structure of the PLP synthase complex with substrate glutamine bound as well as those of the individual synthase and glutaminase subunits Pdx1 and Pdx2, respectively [8].
• It is distinguished by a glutamine amidotransferase, which is remarkable in that it alone can synthesize the cofactor form, pyridoxal 5'-phosphate (PLP), directly from a triose and a pentose saccharide and glutamine [8].
• Thus, our findings of genetic deficiency of PEA- and PLP-phosphatase activity in hypophosphatasia fibroblasts, as well as our biochemical findings, indicate that TNS-ALP acts physiologically as a lipid-anchored PEA and PLP ectophosphatase [1].

Chemical compound and disease context of PDXP

• Although impaired phosphorylation of pyridoxine hydrochloride may be one factor, the most likely explanation for these findings is an increased rate of PLP degradation which may be important in the pathogenesis of vitamin B6 deficiency in patients with severe liver disease [2].
• Since pyridoxal and PLP have been shown to have antisickling properties in vitro, these studies suggest that pyridoxine supplementation may also be of therapeutic benefit in vivo in sickle cell anemia [9].
• RESULTS: Plasma homocysteine was inversely related to serum folate, serum B12, plasma PLP, B vitamin supplement use and Chinese ethnicity, and was positively associated with hypertension, smoking, IMT, MTHFR 677T/T genotype and South Asian ethnicity [10].
• Plasma levels of pyridoxal phosphate (PLP) were determined in 20 patients with pulmonary tuberculosis before and after one week of drug therapy including isoniazid [11].
• Owing to its extensive structural similarity with Mtb Rv1155 and to the E. coli and human PNPOx enzymes, Rv2074 may be involved in the final step in the biosynthesis of pyridoxal 5'-phosphate (PLP; a vitamin B6) [12].

Biological context of PDXP

• Loss of CIN activity blocks phosphocycling of cofilin, stabilizes F-actin structures and causes massive cell division defects [7].
• The PLP co-factor is covalently bound to the active site in the crystal structure, and its binding site is similar to those of other AGTs [13].
• Vitamin B-6 status, assessed by plasma pyridoxal phosphate (PLP) concentrations, and vitamin B-6 concentrations in breast milk were examined in 47 lactating mothers supplemented with different amounts of pyridoxine.HCl (PN.HCl) during pregnancy and the first 6 mo of lactation [14].
• However, there was no significant effect of increased levels of plasma PLP on collagen-stimulated platelet aggregation and only a slight effect on ADP-stimulated aggregation [15].
• Mean plasma PLP levels were normal in patients with stable motor nerve conduction velocity and a low transfusion requirement and low in those with decreasing motor nerve conduction velocity or a high transfusion requirement but the difference between the means in each group was not statistically significant [16].

Anatomical context of PDXP

• Cerebrospinal fluid and urine analyses indicated reduced activity of aromatic L-amino acid decarboxylase and other PLP-dependent enzymes [17].
• In multivariate analyses, PLP was inversely associated with tumor necrosis factor alpha (TNF alpha) production by peripheral blood mononuclear cells (PBMC) (P < 0.001), after adjustment for age, pain score, erythrocyte sedimentation rate, and use of nonsteroidal antiinflammatory drugs [18].
• For PN-treated subjects with low presupplement plasma PLP levels, lymphocyte blastogenesis also increased significantly (p less than 0.01) in response to concanavalin A [19].
• PLP concentrations in cord blood and maternal plasma at 2 d postpartum and vitamin B-6 concentration in colostrum were positively correlated with the amount of PN.HCl supplementation prenatally (r = 0.71, p less than 0.001; r = 0.74, p less than 0.001; and r = 0.78, p less than 0.001, respectively) [14].
• Exercise induces an increase in plasma PLP, perhaps due to transfer of B-6 vitamers from liver to skeletal muscle [20].

Associations of PDXP with chemical compounds

• Obtaining the molecular properties for the human PLP phosphatase may provide new direction for investigating metabolic pathway involving vitamin B6 [21].
• Pyridoxal phosphatase catalyzes the dephosphorylation of pyridoxal 5'-phosphate (PLP) and pyridoxine 5'-phosphate [21].
• Fibroblast ALP has a low-affinity activity, with a distinctly alkaline pH optimum (9.3), toward 4-methylumbelliferyl phosphate (4-MUP), PEA, and PLP but a more physiologic pH optimum (8.3) toward physiologic concentrations (micromolar) of PEA and PLP [1].
• In the mouse, neurotransmitter metabolism can be regulated by modulation of the synthesis of pyridoxal 5'-phosphate and failure to maintain pyridoxal phosphate (PLP) levels results in epilepsy [17].
• The deleterious effect of PLP dissociation from PEG-METase could be improved by supplementing PLP and oleic acid [22].

Other interactions of PDXP

• We report the biochemical isolation of chronophin (CIN), a unique cofilin-activating phosphatase of the haloacid dehalogenase (HAD) superfamily [7].

Analytical, diagnostic and therapeutic context of PDXP

• Plasma pyridoxal-5'-phosphate (PLP) was measured by a specific method in 45 stable, chronic hemodialysis patients and 13 normal adults [16].
• The mean plasma PLP level was 37% lower, (P less than 0.0001), whereas the mean PL level was almost 90% higher (P less than 0.001) in the pregnant group than in the nonpregnant control group [23].
• These SCID mouse-SJL mouse hematopoietic cell chimeras developed passive EAE following adoptive transfer of PLP S139-151-specific SJL T lymphocyte line cells, but were resistant to active EAE induced by primary immunization with PLP S139-151 [24].
• Trace amounts of PLP in the apoenzyme preparation were removed with the aid of cysteine-sulfinic acid and gel filtration [25].
• NGF, BDNF, and PLP were found to be upregulated in OECs cultured on 3-D collagen scaffolds by the semi-quantitative RT-PCR approach [26].

References