Active Form Of Vitamin B6 Research Articles

Hyperhomocysteinemia: a risk factor for placental abruption or infarction

Objective: To establish the prevalence of hyperhomocysteinemia in women with placental abruption or infarction. Design: Forty-six women with normal pregnancy outcome (controls) and 84 women with placental abruption or infarction (study group) were selected, and studied in the non-pregnant state. Homocysteine metabolism was investigated by a standardized oral methionine loading test. Hyperhomocysteinemia was defined as a concentration of fasting and/or postmethionine plasma homocysteine exceeding the estimated 97.5 percentile level of the controls. In the fasting state, the vitamin status was investigated by the measurement of serum and red cell folate, serum vitamin B12, and whole blood pyridoxal-5′-phosphate (PLP, an active form of vitamin B6). Results: Hyperhomocysteinemia was diagnosed in four controls (9%) and 26 women of the study group (31%, P < 0.05). The median concentrations of the vitamins studied were significantly lower in women of the study group as compared to the controls, except for red cell folate, where the median concentration was comparable in both groups. The median concentration of fasting plasma homocysteine, unlike post-methionine plasma homocysteine, was significantly higher in women who experienced placental abruption or infarction in their first pregnancy than in women who had the same event after one or more uncomplicated pregnancies. Conclusion: Hyperhomocysteinemia is associated with placental abruption or infarction.

Modulation of steroid receptor‐mediated gene expression by vitamin B 6

Gene transcription mediated by steroid hormones has become one of the most extensively characterized model systems for studying the regulation of gene expression in eukaryotic cells. However, specific details of gene regulation by steroid hormones are often complex and may be unique in specific cell types. Diverse regulatory mechanisms leading to either activation or repression of particular genes frequently involve interactions between steroid hormone receptors and other ubiquitous and/or cell-specific transcription factors that act on the complex promoter of the regulated gene. Interplay between steroid receptor-mediated and other signal transduction pathways may also be involved. In addition, recent novel results indicate that moderate variations in the intracellular concentration of pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, can have pronounced modulatory effects on steroid-induced gene expression. Specifically, elevation of intracellular PLP levels leads to decreased transcriptional responses to glucocorticoid, progesterone, androgen, or estrogen hormones. Conversely, cells in a vitamin B6-deficient state exhibit enhanced responsiveness to steroid hormones. One aspect of the mechanism by which these transcriptional modulatory effects of PLP occur has recently been shown to involve interruption of functional interactions between steroid hormone receptors and the nuclear transcription factor NF1. These findings--that the vitamin B6 nutritional status of cells modulates their capacity to respond to steroid hormones--impose an additional level of cell-specific control over steroid hormone regulation of gene expression and will serve as the focal point for this review.

Phenelzine Treatment of Panic Disorder

Earlier reports indicated that phenelzine treatment may result in clinically significant reductions of vitamin B6 in some individuals. Sixteen subjects, ages 21-59 years (seven men, nine women) with panic disorder with or without agoraphobia were treated with an average of phenelzine 53.5 mg/day for an average of 10 weeks in an open treatment study. No significant effects on plasma levels of pyridoxal phosphate, the active form of vitamin B6, were discernible in this group, nor was there any clear relationship between pyridoxal phosphate levels and symptoms in the subgroup of five patients who did develop deficiency-type symptoms. Pyridoxine replacement had unclear effects in symptomatic patients.

Pyridoxal 5′-phosphate as an antidote for cyanide, spermine, gentamicin, and dopamine toxicity: An in vivo rat study

Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, readily forms complexes with a wide variety of potentially toxic substances, including cyanide (KCN), spermine (SPM), gentamicin (GM), and dopamine (DOP). The role of PLP as an antidote for these toxicants in vivo was studied. Rats were given intraperitoneal injections of the toxicant, followed by injections of either saline or PLP. For KCN, PLP increased the LD50 from 0.088 to 0.188 mmol/kg and extended the survival time at the highest dose employed from a median of 3 min to a median of 60 min. For SPM, PLP increased the LD50 from 0.162 to 0.262 mmol/kg and prevented death from renal failure at all doses employed except the highest. PLP protected against GM-induced neuromuscular paralysis and death. In the case of DOP, results were equivocal, but no deaths were seen in the PLP-treated rats. The combination of individually nontoxic doses of GM, DOP, and SPM caused death with renal tubular necrosis, pulmonary edema and hemorrhages, congestion of the viscera, and a diffuse coagulopathy. Because many seriously ill patients have elevated SPM levels and are given GM and/or DOP, we suggest that further investigation of the potential protective role of PLP in serious illness be undertaken.

Role of kynurenin and its derivatives in cardiac arrhythmias

Kynurenin is a natural derivative of the essential amino acid, tryptophan, and increased accumulation of kynurenin in the body, or its increased excretion, is regarded as a sensitive indicator of deficiency of pyrixodal-5-phosphate, i.e., the active form of vitamin B6 [2, 3, 6]. No information could be found in the literature on the effect of kynurenin and its derivatives on the genesis of cardiac pathology. In patients with attacks of angina at rest, not responding to nitrites, kynurenin accumulation in the blood serum after administration of Ltryptophan is considerably increased [4]. Correction of intermediate tryptophan metabolism and normalization of kynurenin accumulation in the blood serum are accompanied by improvement of the patient's condition, or even by recovery [5].

Low Levels of Pyridoxal 5'-Phosphate in Patients With Cystic Fibrosis

To determine the effect of cystic fibrosis on the regulation of plasma pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, we measured this compound in plasma from 56 patients with cystic fibrosis. The concentration of PLP in plasma was assayed by a radioenzymatic technique. The results of this study showed that PLP concentration was decreased significantly (6.44 +/- 5.20 ng/mL, mean +/- SD; median 4.45 ng/mL) in patients with cystic fibrosis as compared with a group of hospitalized children with neither cystic fibrosis nor hepatic disease serving as a control group (13.2 +/- 5.04 ng/mL, mean +/- SD; median 12.5 ng/mL). Additionally, 25% of the population with cystic fibrosis exhibited exceedingly low plasma PLP level (less than 2.75 ng/mL). In patients with cystic fibrosis, significant inverse linear associations were found between plasma PLP and serum levels of SGOT and SGPT (PLP v SGOT: r = -.60, P less than .03; PLP v SGPT: r = -.50, P less than .03). This study demonstrated that a deficiency of plasma PLP is a common abnormality in cystic fibrosis and that the low PLP level may be a reflection of impaired vitamin B6 metabolism associated with this disorder.

ウシ胎児大動脈培養細胞に対するビタミンB&lt;sub&gt;6&lt;/sub&gt;阻害剤の影響について

For more than 30 years, we reported that experimental atherosclerosis similar to that of human beings was produced in monkeys by Vitamin B6 deprived diet. However, as the effect of Vitamin B6 on forming atherosclerotic lesion was not obvious, we examined the effect of Vitamin B6 and its antagonists on the cultured endothelial cells from fetal bovine aorta. The patients with homocystinuria, who lack the activity of cystathione synthetase which needs Vitamin B6 as a cofactor, have the tendency to suffer from atherosclerosis in their early life. So it was considered that the impairment of sulfurcontaining amino acid metabolism might play a role in the formation of atherosclerosis in monkeys fed on Vitamin B6 deprived diet. Because the patients with cystathionine synthetase deficiency had homocysteine in their blood at higher concentrations, we also studied the effect of homocysteine and its precursor, S-adenosyl-1-homocysteine.We evaluated the effect of the above substances on the cultured endothelial cells with cell detachment assay by modifying the method of Harker et al. When seeded endothelial cells became confluent in 24 multiwell plate (Corning 25820), test media were added. After 24-hour incubation, each well was washed with PBS and still-adherent cells were counted. Results were expressed as percent detachment compared to control: % Detachment =(Control—Test)/Control×100.We used isoniazid and deoxypyridoxine as Vitamin B6 antagonists. When isoniazid was added, the results were 27.2±1.7%, 49.4±5.7%, 52.8±3.5% at concentration 1mM, 2.5mM, 5mM, respectively. When deoxypyridoxine was added, the results were 12.3±8.3%, 25.4±7.0%, 41.9±2.7% at concentration 0.5mM, 1mM, 2.5mM, respectively. On the other hand, we used pyriodoxal phosphate, active form of Vitamin B6, and pyridoxal HCl as Vitamin B6. When pyridoxal phosphate was added, the results were 0.9±3.6%, 4.4±2.5%, 8.1±2.2% at concentration 0.01mM, 0.1mM, 1mM, respectively. When pyridoxal HCl was added, the results were 7.5±1.5%, 11.7±4.1%, 18.9±2.6% at concentration 0.01mM, 0.1mM, 1mM, respectively. Also sulfur containing amino acids, DL-homocysteine and S-adenosyl-1-homocysteine was tested. When DL-homocysteine was added, the results were 2.8±6.4%, 19.0±6.3%, 16.5±6.3% at concentration 0.5mM, 1mM, 2mM, respectively. When S-adenosyl-1-homo-cysteine was added, the results were 24.2±9.1%, 32.9±7.3%, 33.2±8.1% at concentration 0.5mM, 1mM, 2mM, respectively.The role of Vitamin B6 deficiency in the formation of atherosclerosis is not clear in this study, which uses endothelial cells alone in vitro. However, it was interesting that Vitamin B6 itself, as well as its antagonists, had endothelial detaching potential, although tested drug concentrations had to be taken into consideration. It was supposed that the atherosclerosis may be caused by the impairment of multiple factors, for example, not only endothelial cells but also smooth muscle cells, platelets, coagulants and their interactions in vivo. Vitamin B6 depletion may also take part in the formation of atherosclerosis by influencing many factors but many problems regarding these mechanisms still remain to be clarified.

EFFECT OF PCB (POLYCHLOROBIPHENYLS) ON L-ASCORBIC ACID, PYRIDOXAL PHOSPHATE AND RIBOFLAVIN CONTENTS IN VARIOUS ORGANS AND ON HEPATIC METABOLISM OF L-ASCORBIC ACID IN THE RAT

Effects of continuous oral administration of PCB (polychlorobiphenyls, 10-100 mg/kg/day, 4 weeks) on tissue levels of L-ascorbic acid (vitamin C), pyridoxal phosphate and riboflavin (vitamin B2) in various organs and on hepatic metabolism of L-ascorbic acid were examined in male Wistar rats weighing 150-250 g. Riboflavin contents in the liver, kidney, brain, heart and testis were not altered by PCB treatments, whereas the hepatic level of pyridoxal phosphate, a biologically active form of vitamin B6, was significantly reduced by PCB administration. Under the same experimental conditions, L-ascorbic acid contents in the liver, kidney, lung and testis showed a significant increase. Histochemical studied revealed that in the adrenal gland, increase of L-ascorbic acid was localized in the fasciculate and reticular zones of cortex, respectively. It was found that increase of L-ascorbic acid in the liver is caused predominantly by activation of biosynthesis at the steps of galactose to D-glucuronic acid and is not due to changes in the catabolic processes of L-ascorbic acid per se. Possible significance of these changes in tissue levels and/or metabolism of vitamins in the occurrence of PCB intoxication is briefly discussed.

Biochemical assessment of the nutritional status of vitamin B6 in the human

It has been found that the human body stores only a small amount of Vitamin-B6 and can quickly be depleted of this vitamin. Pyridoxal phosphate is the active form of Vitamin-B6. Normal adults have blood plasma levels of Vitamin-B6 in excess of 50 ng/ml whereas in those with a deficiency the levels fall below 25 ng/ml. In a study of 172 alcoholic patients 25% of those with liver cirrhosis had low serum Vitamin-B6 levels. In a group of New York City schoolchildren a serum level of 36 ng/ml of B6 was determined. The vitamin appears in the urine mainly as pyridoxal but also as pyridoxamine and pyridoxine. A rapid decrease in excretion has been noted when patients received only .16 mg of Vitamin-B 6 daily. A daily supplement of 1.5 mg of pyridoxine corrected this. Age differences in excretion have been shown with children excreting more than adults. The ingestion of oral contraceptives did not alter the excretion of Vitamin-B6. Normal subjects excrete .5-1.3 mg of 4-pyridoxic acid a day. This represents 40% of daily ingested Vitamin-B6. Thus a 2 mg daily intake of Vitamin-B6 would result in a daily excretion of .8 mg of 4-pyridoxic acid. Tryptophan metabolism has been shown to be influenced by Vitamin-B6 dietary restriction. Following a loading dose of tryptophan excretion of xanthurenic acid and other tryptophan metabolites have been increased. This test has been used for detecting Vitamin-B6 deficiency. Prolonged fasting modifies interpretation of this test and oral contraceptives containing estrogen and progsterone increase the amounts of tryptophan metabolites in the urine. Large doses of pyridoxine supplements correct this increase in urinary metabolites. Transaminase activities in erythrocytes leukocytes and plasma have been used as measurements of Vitamin-B6 nutritional status. Other tests have been suggested but have not been shown to be better.

CONVERSION OF CYANO- AND HYDROXO-COBALAMIN IN VIVO INTO CO-ENZYME FORM OF VITAMIN B12 IN THE RAT.

SINCE 5,6-dimethylbenzimidazolyl cobamide co-enzyme (DBCC) was shown to be one of the active forms of vitamin B12 by Barker et al. in 1959 (ref. 1), its biochemical co-enzymatic activity (conversion of glutamate to methyl aspartate, methyl malonyl–CoA to succinyl–CoA, and 1,2-diols to aldehydes) and its physiological metabolism (tissue distribution, excretion and absorption) have been investigated2–8. It is now believed that vitamin B12 exists as a co-enzyme form in the liver, and takes part in the transformation of methyl malonyl–CoA to succinyl–CoA (ref. 9). On the other hand, enzymatic synthesis of DBCC from B12 derivatives has been confirmed by several workers at the bacterial enzymatic level. It has been reported that the liver and kidney homogenate of rat could convert cyanocobalamin (CN–B12) to co-enzyme B12 in vitro10. But the only report indicating that CN–B12 or hydroxocobalamin (OH–B12) can be converted to co-enzyme form in vivo, on the quantitative base, is Fenrych's short communication reporting the conversion of CN–B12 into the co-enzyme form in rabbit11. Our preliminary report concerning this conversion, which was obtained by 57Co-labelling of the DBCC fraction in rat liver following the intravenous administration of 57Co-labelled CN–B12 and 57Co-labelled OH–B12 in rat, will be described here.

Support for Belgian Doctors

<h3>Background</h3> The active form of vitamin B6, called pyridoxal-5-phosphate (P5P), is an essential cofactor for several enzymes involved in various pathways of intermediary metabolism. PNPO is the rate-limiting enzyme in the synthesis of pyridoxal from vitamin B6 and a lack of activity causes dependency on an external source of pyridoxal. Epileptic seizure is the clinical outcome of P5P deficiency. <h3>Purpose</h3> To provide a dosage form suitable for newborns and children. Capsules containing standardised P5P were compounded. Moreover, a fully soluble powder blend was formulated to fill the capsules and a method to determine the stability of the P5P content was developed. <h3>Materials and Methods</h3> Dissolution assays were performed using oral syringes as nurses do. Time to complete dissolution and concentration were determined at each test. P5P content was determined by HPLC-UV (205 nm). The mobile phase consisted of phosphate buffer (0.05 M; pH 2.6) at a flow rate of 1 ml/min. The right active ingredient was tested by adding vitamin B6 to samples. Degradation by-products in stress conditions were also determined. The method was validated according to ICH recommendations. <h3>Results</h3> Strengths were standardised at 10, 25, 50, 100 or 250 mg/capsule. The adopted blend is quickly solubilised in water and has a sweet taste. The HPLC readings were linear (r² = 0.9994) at the wavelength used, indicating good reproducibility and repeatability (SD = 0.46%). No matrix effect due to the diluent was observed. <h3>Conclusions </h3> As P5P is a low toxicity compound, a test treatment with P5P is given to every newborn with idiopathic seizure before any treatment with standard antiepileptics. This method allows rapid routine assay of P5P. Stability testing of 3 compounded batches is ongoing. No conflict of interest.

Pyruvate oxidation in brain

Research Article| July 01 1939 Pyruvate oxidation in brain: The active form of vitamin B1 and the role of C4 dicarboxylic acids Ilona Banga; Ilona Banga 1The Department of Biochemistry, Oxford Search for other works by this author on: This Site PubMed Google Scholar Severo Ochoa; Severo Ochoa 1The Department of Biochemistry, Oxford Search for other works by this author on: This Site PubMed Google Scholar Rudolph Albert Peters Rudolph Albert Peters 1The Department of Biochemistry, Oxford Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1939) 33 (7): 1109–1121. https://doi.org/10.1042/bj0331109 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Cite Icon Cite Get Permissions Citation Ilona Banga, Severo Ochoa, Rudolph Albert Peters; Pyruvate oxidation in brain: The active form of vitamin B1 and the role of C4 dicarboxylic acids. Biochem J 1 July 1939; 33 (7): 1109–1121. doi: https://doi.org/10.1042/bj0331109 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1939 CAMBRIDGE UNIVERSITY PRESS1939 Article PDF first page preview Close Modal You do not currently have access to this content.

Active Form of Vitamin B1 in Tissues

THOUGH there has been a strong indication since the work of Lohmann and Schuster1 that the active form of vitamin B1 in pigeon brain tissue is phosphorylated, the failure to obtain much activity with cocarboxylase in the catatorulin test with “brei” or slices has made it impossible to make a firm decision2,3. We are now able to report that with the use of two types of finely ground “avitaminous” brain preparations (in presence of fumarate) we can get either (1) a preparation which shows good catatorulin effects with small amounts of cocarboxylase (0.26 max.) and practically no effect with vitamin B1, or (2) one which still retains some catatorulin effect with large amounts of vitamin B1 (10 I3) as well as good effects with small amounts of cocarboxylase. Both preparations are rather unstable; the medium vised is as in previous experiments.