Relationship Between Vitamin B-6 Status and Elevated Pyridoxal Kinase Levels Induced by Theophylline Therapy in Humans

1990 ◽  
Vol 120 (11) ◽  
pp. 1352-1359 ◽  
Author(s):  
Johan B. Ubbink ◽  
Rhena Delport ◽  
Siegbert Bissbort ◽  
W. J. Hayward Vermaak ◽  
Piet J. Becker
Keyword(s):  
Vitamin B ◽  
Pyridoxal Kinase

scholarly journals Inhibiting Pyridoxal Kinase of Entamoeba histolytica Is Lethal for This Pathogen

2021 ◽  
Vol 11 ◽  
Author(s):  
Suneeta Devi ◽  
Priya Tomar ◽  
Khaja Faisal Tarique ◽  
Samudrala Gourinath
Keyword(s):  
Entamoeba Histolytica ◽  
Drug Targets ◽  
Cultured Cells ◽  
De Novo ◽  
Active Form ◽  
Protozoan Parasite ◽  
Vitamin B ◽  
Pyridoxal Kinase ◽  
Small Molecule Libraries

Pyridoxal 5’-phosphate (PLP) functions as a cofactor for hundreds of different enzymes that are crucial to the survival of microorganisms. PLP-dependent enzymes have been extensively characterized and proposed as drug targets in Entamoeba histolytica. This pathogen is unable to synthesize vitamin B6via de-novo pathway and relies on the uptake of vitamin B6 vitamers from the host which are then phosphorylated by the enzyme pyridoxal kinase to produce PLP, the active form of vitamin B6. Previous studies from our lab shows that EhPLK is essential for the survival and growth of this protozoan parasite and its active site differs significantly with respect to its human homologue making it a potential drug target. In-silico screening of EhPLK against small molecule libraries were performed and top five ranked molecules were shortlisted on the basis of docking scores. These compounds dock into the PLP binding site of the enzyme such that binding of these compounds hinders the binding of substrate. Of these five compounds, two compounds showed inhibitory activity with IC50 values between 100-250 μM when tested in-vitro. The effect of these compounds proved to be extremely lethal for Entamoeba trophozoites in cultured cells as the growth was hampered by 91.5% and 89.5% when grown in the presence of these compounds over the period of 72 hours.

Mechanism of pyridoxine 5'-phosphate accumulation in PLPBP protein-deficiency

2022 ◽  
Author(s):  
Tomokazu Ito ◽  
Honoka Ogawa ◽  
Hisashi Hemmi ◽  
Diana M. Downs ◽  
Tohru Yoshimura
Keyword(s):  
De Novo ◽  
Binding Protein ◽  
Vitamin B ◽  
Wild Type ◽  
Salvage Pathway ◽  
Intracellular Accumulation ◽  
Pyridoxal Kinase ◽  
Genetic Studies ◽  
E Coli ◽  
Metabolic Systems

The pyridoxal 5'-phosphate (PLP)-binding protein (PLPBP) plays an important role in vitamin B 6 homeostasis. Loss of this protein in organisms such as Escherichia coli and humans disrupts the vitamin B 6 pool and induces intracellular accumulation of pyridoxine 5'-phosphate (PNP), which is normally undetectable in wild-type cells. The accumulated PNP could affect diverse metabolic systems through inhibition of some PLP-dependent enzymes. In this study, we investigated the as yet unclear mechanism of intracellular accumulation of PNP by the loss of PLPBP protein encoded by yggS in E. coli . Genetic studies using several PLPBP-deficient strains of E. coli lacking known enzyme(s) in the de novo or salvage pathway of vitamin B 6 , which includes pyridoxine (amine) 5'-phosphate oxidase (PNPO), PNP synthase, pyridoxal kinase, and pyridoxal reductase, demonstrated that neither the flux from the de novo pathway nor the salvage pathway solely contributed to the PNP accumulation caused by the PLPBP mutation. Studies with the strains lacking both PLPBP and PNPO suggested that PNP shares the same pool with PMP, and showed that PNP levels are impacted by PMP levels and vice versa . We show that disruption of PLPBP lead to perturb PMP homeostasis, which may result in PNP accumulation in the PLPBP-deficient strains. Importance A PLP-binding protein PLPBP from the conserved COG0325 family has recently been recognized as a key player in vitamin B 6 homeostasis in various organisms. Loss of PLPBP disrupts vitamin B 6 homeostasis and perturbs diverse metabolisms, including amino acid and α-keto acid metabolism. Accumulation of PNP is a characteristic phenotype of the PLPBP deficiency and is suggested to be a potential cause of the pleiotropic effects, but the mechanism of the PNP accumulation was poorly understood. In this study, we show that fluxes for PNP synthesis/metabolism are not responsible for the accumulation of PNP. Our results indicate that PLPBP is involved in the homeostasis of pyridoxamine 5'-phosphate, and its disruption may lead to the accumulation of PNP in PLPBP-deficiency.

scholarly journals Successful data recovery from oscillation photographs containing strong polycrystalline diffraction rings from an unknown small-molecule contaminant: preliminary structure solution ofSalmonella typhimuriumpyridoxal kinase (PdxK)

2014 ◽  
Vol 70 (4) ◽  
pp. 526-529 ◽  
Author(s):  
G. Deka ◽  
J. N. Kalyani ◽  
J. F. Benazir ◽  
H. S. Savithri ◽  
M. R. N. Murthy
Keyword(s):  
Small Molecule ◽  
Vitamin B ◽  
Molecular Replacement ◽  
X Ray Diffraction ◽  
Pyridoxal Kinase ◽  
Orthorhombic Space Group ◽  
X Ray ◽  
Cell Parameters ◽  
E Coli ◽  
Structure Solution

Pyridoxal kinase (PdxK; EC 2.7.1.35) belongs to the phosphotransferase family of enzymes and catalyzes the conversion of the three active forms of vitamin B6, pyridoxine, pyridoxal and pyridoxamine, to their phosphorylated forms and thereby plays a key role in pyridoxal 5′-phosphate salvage. In the present study, pyridoxal kinase fromSalmonella typhimuriumwas cloned and overexpressed inEscherichia coli, purified using Ni–NTA affinity chromatography and crystallized. X-ray diffraction data were collected to 2.6 Å resolution at 100 K. The crystal belonged to the primitive orthorhombic space groupP212121, with unit-cell parametersa= 65.11,b= 72.89,c= 107.52 Å. The data quality obtained by routine processing was poor owing to the presence of strong diffraction rings caused by a polycrystalline material of an unknown small molecule in all oscillation images. Excluding the reflections close to powder/polycrystalline rings provided data of sufficient quality for structure determination. A preliminary structure solution has been obtained by molecular replacement with thePhaserprogram in theCCP4 suite usingE. colipyridoxal kinase (PDB entry 2ddm) as the phasing model. Further refinement and analysis of the structure are likely to provide valuable insights into catalysis by pyridoxal kinases.

scholarly journals Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity

2021 ◽  
Author(s):  
Felix Hadtstein ◽  
Misha Vrolijk
Keyword(s):  
Peripheral Neuropathy ◽  
Sensory Neurons ◽  
Sensory Neuropathy ◽  
Vitamin B ◽  
Hereditary Neuropathy ◽  
Pyridoxal Kinase ◽  
Peripheral Tissues ◽  
Adverse Health Effects ◽  
Gaba Signaling ◽  
Gaba Neurotransmission

ABSTRACT Vitamin B-6 in the form of pyridoxine (PN) is commonly used by the general population. The use of PN-containing supplements has gained lots of attention over the past years as they have been related to the development of peripheral neuropathy. In light of this, the number of reported cases of adverse health effects due to the use of vitamin B-6 have increased. Despite a long history of study, the pathogenic mechanisms associated with PN toxicity remain elusive. Therefore, the present review is focused on investigating the mechanistic link between PN supplementation and sensory peripheral neuropathy. Excessive PN intake induces neuropathy through the preferential injury of sensory neurons. Recent reports on hereditary neuropathy due to pyridoxal kinase (PDXK) mutations may provide some insight into the mechanism, as genetic deficiencies in PDXK lead to the development of axonal sensory neuropathy. High circulating concentrations of PN may lead to a similar condition via the inhibition of PDXK. The mechanism behind PDXK-induced neuropathy is unknown; however, there is reason to believe that it may be related to γ-aminobutyric acid (GABA) neurotransmission. Compounds that inhibit PDXK lead to convulsions and reductions in GABA biosynthesis. The absence of central nervous system-related symptoms in PDXK deficiency could be due to differences in the regulation of PDXK, where PDXK activity is preserved in the brain but not in peripheral tissues. As PN is relatively impermeable to the blood–brain barrier, PDXK inhibition would similarly be confined to the peripheries and, as a result, GABA signaling may be perturbed within peripheral tissues, such as sensory neurons. Perturbed GABA signaling within sensory neurons may lead to excitotoxicity, neurodegeneration, and ultimately, the development of peripheral neuropathy. For several reasons, we conclude that PDXK inhibition and consequently disrupted GABA neurotransmission is the most plausible mechanism of toxicity.

scholarly journals Effect of tryptophan metabolites on the activities of rat liver pyridoxal kinase and pyridoxamine 5-phosphate oxidase in vitro

1985 ◽  
Vol 227 (2) ◽  
pp. 537-544 ◽  
Author(s):  
F Takeuchi ◽  
R Tsubouchi ◽  
Y Shibata
Keyword(s):  
Rat Liver ◽  
Substrate Inhibition ◽  
Maximum Velocity ◽  
Vitamin B ◽  
Pyridoxal Kinase ◽  
Tryptophan Metabolites

Pyridoxal kinase was purified 4760-fold from rat liver. The Km values for pyridoxine and pyridoxal were 120 and 190 microM respectively, and pyridoxine showed substrate inhibition at above 200 microM. Pyridoxamine 5-phosphate oxidase was also purified 2030-fold from rat liver, and its Km values for pyridoxine 5-phosphate and pyridoxamine 5-phosphate were 0.92 and 1.0 microM respectively. Pyridoxine 5-phosphate gave a maximum velocity that was 5.6-fold greater than with pyridoxamine 5-phosphate and showed strong substrate inhibition at above 6 microM. Among the tryptophan metabolites, picolinate, xanthurenate, quinolinate, tryptamine and 5-hydroxytryptamine inhibited pyridoxal kinase. However, pyridoxamine 5-phosphate oxidase could not be inhibited by tryptophan metabolites, and on the contrary it was activated by 3-hydroxykynurenine and 3-hydroxyanthranilate. Regarding the metabolism of vitamin B-6 in the liver, the effects of tryptophan metabolites that were accumulated in vitamin B-6-deficient rats after tryptophan injection were discussed.

Schutz vor Insekten

2005 ◽  
Vol 62 (11) ◽  
pp. 713-718 ◽  
Author(s):  
Rudin
Keyword(s):  
Vitamin B ◽  
Eucalyptus Citriodora ◽  
Knock Down

Erfolgreicher Schutz gegen Stiche von blutsaugenden Insekten und Zecken bedingt die konsequente Anwendung geeigneter Maßnahmen. Eine eventuell notwendige Chemoprophylaxe wird dadurch nie ersetzt. Die Umstände, unter denen der Schutz erreicht werden soll, bestimmen die Kombination der zu treffenden Maßnahmen. Von Wohnräumen kann man Insekten mit Mückengittern oder -gaze an Fenstern und Türen oder mittels Klimaanlagen fernhalten. Beim Schlafen kann man sich mit einem Moskitonetz schützen. Diese Maßnahmen können bei Bedarf durch Insektizide ergänzt oder unterstützt werden. Meistens kommen synthetische Pyrethroide entweder als «knock down»-Sprays oder elektroverdampft für die Behandlung von Räumen oder als Imprägnierungsmittel von Netzen und Gittern zum Einsatz. Wenn ein Kontakt nicht durch die Wahl von Aufenthaltsort und -zeit vermeidbar ist, werden außer Haus zum Schutz vor Stichen geeignete Kleidung sowie Repellentien eingesetzt. Kleider sollen möglichst viel Körperfläche bedecken, aus festem Gewebe, nicht eng anliegend und von heller Farbe sein. Eine zusätzliche Behandlung mit Insektiziden ist vorteilhaft. Repellentien werden direkt auf die Haut appliziert. Diethylmethylbenzamin (DEET) zeigt seit vielen Jahren eine verlässliche Wirkung. Ebenfalls verbreitete synthetische Wirkstoffe sind Bayrepel® und IR3535. Sie weisen ein noch etwas geringeres Nebenwirkungsrisiko auf, nachteilig ist jedoch die schwächere Wirkung. Von den pflanzlichen Produkten sind die mit einem Extrakt aus Eucalyptus citriodora die am besten wirksamen. Schwächere Produkte schützen Personen, die für Mücken speziell attraktiv sind, nur ungenügend. Völlig nutzlos sind auf Arm-, Halsbänder oder Kleber aufgetragene Repellentien, sowie Ultraschallgeräte, UV-Lichtfallen oder die Einnahme von Vitamin B1 oder Knoblauch.

Nutritional B12 Deficiency in Infants of Vitamin B12-Deficient Mothers

2011 ◽  
Vol 81 (5) ◽  
pp. 328-334 ◽  
Author(s):  
Oya Halicioglu ◽  
Sezin Asik Akman ◽  
Sumer Sutcuoglu ◽  
Berna Atabay ◽  
Meral Turker ◽  
...  
Keyword(s):  
Megaloblastic Anemia ◽  
Maternal Diet ◽  
Clinical Manifestations ◽  
Serum Vitamin ◽  
Failure To Thrive ◽  
Clinical Findings ◽  
Vitamin B ◽  
Animal Products ◽  
Hematological Evaluation ◽  
Nutritional Vitamin

Aim: Nutritional vitamin B12 deficiency in infants may occur because the maternal diet contains inadequate animal products. Clinical presentations of the infants who had nutritional vitamin B12 deficiency were analyzed in this study. Subjects and Methods: Patients with nutritional vitamin B12 deficiency were enrolled in the study between 2003 and 2010. The diagnosis was based on a nutritional history of mothers and infants, clinical findings, hematological evaluation, and low level of serum vitamin B12. Results: Thirty children aged 1 - 21 months constituted the study group. Poverty was the main cause of inadequate consumption of animal products of the mothers. All infants had predominantly breastfed. The most common symptoms were developmental delay, paleness, apathy, lethargy, anorexia, and failure to thrive. Hematological findings were megaloblastic anemia (83.3 %), thrombocytopenia (30 %), and severe anemia (13.3 %). All of the mothers had low serum B12 levels; eight of them had megaloblastic anemia. Conclusion: The unusual clinical manifestations of vitamin B12 deficiency may also be seen apart from neurological and hematological findings. Nutritional vitamin B12 deficiency due to maternal deficiency might be a serious health problem in infants. Therefore, screening and supplementation of pregnant and lactating women to prevent infantile vitamin B12 deficiency should be considered.

Vitamin B6 Deficiency can Reduce Fuel Storage and Utilization in Physically Trained Rats

2008 ◽  
Vol 78 (2) ◽  
pp. 64-69 ◽  
Author(s):  
Choi ◽  
Cho
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Muscle Protein ◽  
Plasma Free Fatty Acid ◽  
Vitamin B ◽  
Liver Protein ◽  
Protein Levels ◽  
Before And After ◽  
Fuel Storage ◽  
Exercise Muscle

This study investigated the effect of vitamin B6 deficiency on the utilization and recuperation of stored fuel in physically trained rats. 48 rats were given either vitamin B6-deficient (B6–) diet or control (B6+) diet for 4 weeks and were trained on treadmill for 30 minutes daily. All animals were then subdivided into 3 groups: before-exercise (BE); during-exercise (DE); after-exercise (AE). The DE group was exercised on treadmill for 1 hour just before being sacrificed. Animals in the AE group were allowed to take a rest for 2 hours after being exercised like the DE group. Glucose and free fatty acids were compared in plasma. Glycogen and triglyceride were compared in liver and skeletal muscle. Protein levels were compared in plasma, liver, and skeletal muscle. Compared with the B6+ group, plasma glucose levels of the B6– group were significantly lower before and after exercise. Muscle glycogen levels of the B6– group were significantly lower than those of the B6+ group regardless of exercise. The liver glycogen level of the B6– group was also significantly lower than that of B6+ group during and after exercise. Before exercise, plasma free fatty acid levels were not significantly different between the B6+ and B6– groups, and plasma free fatty acid levels of the B6– group were significantly lower during and after exercise. The muscle triglyceride level of the B6– group was significantly lower than that of the B6+ group before exercise, and there were no differences between B6+ and B6– groups during and after exercise. Liver triglyceride levels were not significantly different between B6+ and B6– groups. Plasma protein levels of the B6– group were lower than those of B6+ before and after exercise. Muscle protein levels of the B6– group were not significantly different from those of the B6+ group. Liver protein levels of the B6– group were significantly lower than that of the B6+ group after exercise. Liver protein levels of both B6+ and B6– groups were not significantly changed, regardless of exercise. Thus, it is suggested that vitamin B6 deficiency may reduce fuel storage and utilization with exercise in physically trained rats.

Homocysteine Levels Show Significant Differences among Mediterranean Dietary Quality Index Variables Compared to Folate and Vitamin B12 Status in Women

2015 ◽  
Vol 85 (3-4) ◽  
pp. 202-210 ◽  
Author(s):  
Ivona Višekruna ◽  
Ivana Rumbak ◽  
Ivana Rumora Samarin ◽  
Irena Keser ◽  
Jasmina Ranilović
Keyword(s):  
Mediterranean Diet ◽  
Diet Quality ◽  
Quality Index ◽  
Fruits And Vegetables ◽  
Reproductive Age ◽  
Dietary Quality ◽  
Vitamin B ◽  
Cross Sectional ◽  
Poor Diet ◽  
The Mediterranean

Abstract. Results of epidemiologic studies and clinical trials have shown that subjects following the Mediterranean diet had lower inflammatory markers such as homocysteine (Hcy). Therefore, the aim of this cross-sectional study was to assess female diet quality with the Mediterranean diet quality index (MDQI) and to determine the correlation between MDQI, homocysteine, folate and vitamin B12 levels in the blood. The study participants were 237 apparently healthy women (96 of reproductive age and 141 postmenopausal) between 25 and 93 years. For each participant, 24-hour dietary recalls for 3 days were collected, MDQI was calculated, and plasma Hcy, serum and erythrocyte folate and vitamin B12 levels were analysed. Total MDQI ranged from 8 to 10 points, which represented a medium-poor diet for the subjects. The strength of correlation using biomarkers, regardless of group type, age, gender and other measured parameters, was ranked from best (0.11) to worst (0.52) for olive oil, fish, fruits and vegetables, grains, and meat, in this order. Hcy levels showed the best response among all markers across all groups and food types. Our study shows significant differences between variables of the MDQI and Hcy levels compared to levels of folate and vitamin B12 in participants with medium-poor diet quality, as evaluated according to MDQI scores.

Serum Vitamin B12 Concentrations among Mothers and Newborns and Follow-up Study to Assess Implication on the Growth Velocity and the Urinary Methylmalonic Acid Excretion

2009 ◽  
Vol 79 (56) ◽  
pp. 297-307 ◽  
Author(s):  
Laila Hussein ◽  
Sahar Abdel Aziz ◽  
Salwa Tapouzada ◽  
Boehles
Keyword(s):  
Early Diagnosis ◽  
Growth Velocity ◽  
Methylmalonic Acid ◽  
Post Partum ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Postnatal Life ◽  
Negative Consequences ◽  
Metabolic Marker ◽  
Biochemical Measurement

Objective:Cobalamin (B12) deficiency has been reported in infants born to mothers with low cobalamin intake. Early diagnosis of vitamin B12 deficiency in infants is critical for the prevention of neurobehavioral disorders. We investigated the relationship between serum vitamin B12 level in newborns and in their healthy mothers who consumed an omnivorous diet. Anthropometry was studied longitudinally to assess the growth velocity of the infants. Urinary methylmalonic acid (MMA) excretion of 6-month old infants was compared retrospectively as the biomarker correlated with the initial serum vitamin B12 concentrations. Methods: Serum cobalamin and blood hemoglobin were determined in 84 pairs of newborns and their mothers. Urinary MMA excretion was measured in the same subjects during the first 6 months of the post partum period. Results: At birth, median serum cobalamin levels were 152.0 pmol/L in the mothers and 296.6 pmol/L in the newborns. Maternal and neonatal serum cobalamin levels had no effect on growth velocity during the first six months of postnatal life. Serum maternal and neonatal cobalamin levels were inversely associated with urinary MMA excretion. Conclusion: Early diagnosis of vitamin B12 status in neonates and infants is crucial, particularly in nutritionally deprived areas. Biochemical measurement of plasma cobalamin or its metabolic marker MMA is highly recommended. Urinary MMA measurement in cobalamin diagnostics provides an advantage in that blood sampling is not required. A vitamin B12 taskforce should be created to alleviate vitamin deficiency and its negative consequences.

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