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J B Ubbink

Publications and source records attributed to J B Ubbink.

At least 73 records · Page 4Linked to original sources
PubMed1990

Relationship between vitamin B-6 status and elevated pyridoxal kinase levels induced by theophylline therapy in humans.

Theophylline administration to seven healthy male volunteers resulted in a rapid and significant decline in both plasma and erythrocyte pyridoxal-5'-phosphate levels. Total erythrocyte pyridoxal kinase levels increased during 15 wk of theophylline treatment from a mean initial activity of 19.23 +/- 5.03 (mean +/- SD) to 62.64 +/- 11.59 nmol pyridoxal-5'-phosphate formed/(g hemoglobin.h). Although plasma pyridoxal levels remained normal, the threefold increase in total erythrocyte pyridoxal kinase activity levels did not normalize plasma and erythrocyte pyridoxal-5'-phosphate levels. Pyridoxal-5'-phosphate hydrolysis was not affected by theophylline therapy. Increased pyridoxal oxidation was confirmed by elevated urinary 4-pyridoxic acid excretion after 15 wk of theophylline treatment. Mean erythrocyte alanine aminotransferase activity declined by 70%, and aspartate aminotransferase activity declined by 50%, indicating that decreased availability of pyridoxal-5'-phosphate can have widespread metabolic consequences. We conclude that the effect of theophylline on vitamin B-6 metabolism is not transitory and cannot be overcome by elevated intracellular levels of pyridoxal kinase. However, pyridoxine supplementation (10 mg/d for 1 wk) normalized indices of vitamin B-6 status and reversed the downward trend in both alanine aminotransferase and aspartate aminotransferase activity levels.

Adult↗
PubMed1990

Inhibition of pyridoxal kinase by methylxanthines.

In the presence of saturating concentrations of adenosine triphosphate (ATP) and rate-limiting amounts of pyridoxal, theophylline was found to inhibit sheep brain pyridoxal kinase (EC 2.7.1.35) competitively. The apparent inhibition constant (Ki) of theophylline for pyridoxal kinase was determined as 8.7 mumol/l. Theophylline concentrations of up to 60 mumol/l did not affect pyridoxal phosphorylation in the presence of saturating amounts of pyridoxal and rate-limiting concentrations of ATP. Caffeine was less potent to inhibit pyridoxal kinase (Ki = 45 mumol/l) due to the presence of a methyl group on the 7 position of the xanthine ring structure. Theobromine showed only a weak inhibition of pyridoxal kinase (Ki = 453 mumol/l). The presence of a hydroxyethyl, hydroxypropyl or dihydroxypropyl group on the N7 position of theophylline completely abolished inhibition of pyridoxal kinase. Enprofylline (3-propylxanthine), a recently described bronchodilator, was also able to inhibit pyridoxal kinase with a Ki of 256 mumol/l.

Animals↗
PubMed1990

Altered vitamin B6 homeostasis during aminophylline infusion in the beagle dog.

The effect of intravenous infusion of aminophylline, a strong inhibitor of pyridoxal kinase, on intra- and extracellular vitamin B6 homeostasis was investigated in four beagle dogs. Plasma and erythrocyte pyridoxal levels increased by 118% and 117% respectively after 3 hours of aminophylline infusion, (4 mg/kg body weight/hour), however, infusion of beta-hydroxyethyltheophylline, which does not inhibit pyridoxal kinase, had no effect on either intra- or extracellular vitamin B6 aldehyde derivative levels. It is suggested that theophylline induced pyridoxal kinase inhibition resulted in a disturbed equilibrium between pyridoxal and pyridoxal 5'-phosphate.

Alkaline Phosphatase↗
PubMed1989

Genetic polymorphism of glutamate-pyruvate transaminase (alanine aminotransaminase): influence on erythrocyte activity as a marker of vitamin B-6 nutritional status.

A new, sensitive, two-step method free from interference by hemoglobin that measures erythrocyte glutamate-pyruvate transaminase (E-GPT) activity is described. Several aspects of E-GPT activity as an index of vitamin B-6 nutritional status were investigated with this method. 1) GPT shows a structural genetic polymorphism with two common alleles resulting in three phenotypes. In a population study (n = 92) E-GPT activity differed significantly (p less than 0.001) among the three phenotypic groups. Plasma pyridoxal-5'-phosphate concentrations in the three groups did not differ significantly. Therefore, E-GPT activity can only be used to assess vitamin B-6 nutritional status if GPT phenotype is accounted for. 2) Pyridoxine supplementation (10 mg/d) significantly (p less than 0.0001) increased E-GPT activity and decreased (p less than 0.0001) the percentage stimulation by pyridoxal-5'-phosphate in vitro although the absolute amount of in vitro stimulation by pyridoxal-5'-phosphate changed only marginally. 3) Inorganic phosphate inhibits in vitro activation of E-GPT by pyridoxal-5'-phosphate.

Alanine Transaminase↗
PubMed1989

Evidence of a theophylline-induced vitamin B6 deficiency caused by noncompetitive inhibition of pyridoxal kinase.

A placebo-controlled, double-blind study indicated that theophylline administration to apparently healthy, young men induced significantly depressed plasma pyridoxal-5'-phosphate levels. Plasma pyridoxal levels were not affected by theophylline therapy. The effect of theophylline on circulating pyridoxal-5'-phosphate levels is explained by the observation that theophylline acts as a noncompetitive inhibitor for erythrocyte pyridoxal kinase (EC 2.7.1.35) with an apparent inhibition constant (Ki) of 1.28 x 10(-5) mol/L. Theophylline did not affect erythrocyte pyridoxamine (pyridoxine)-5'-phosphate oxidase (EC 1.4.3.5) activity. During theophylline therapy, erythrocyte pyridoxal kinase levels increased nearly twofold from an initial mean level of 24.2 +/- 4.0 (+/- SD) nmol to 46.9 +/- 7.3 nmol pyridoxal-5'-phosphate per gram of hemoglobin per hour. This partially counteracted the effect of theophylline on vitamin B6 metabolism. Nevertheless, erythrocyte pyridoxal-5'-phosphate levels in subjects given theophylline decreased significantly (p = 0.03) from pretreatment levels. The oral tryptophan load test resulted in significantly (p = 0.007) increased urinary xanthurenic acid excretion after 4 weeks of theophylline therapy. Both plasma pyridoxal-5'-phosphate levels and the tryptophan load test results normalized after 1 week of pyridoxine supplementation, indicating that 10 mg pyridoxine per day was effective to counteract the antagonistic effect of short-term theophylline therapy on vitamin B6 metabolism.

Adult↗
PubMed1988

Influence of a habitual high egg intake on serum lipid levels in a rural coloured population.

The effect of a habitual high cholesterol intake on serum cholesterol and other lipid levels against the background of a moderate fat intake was investigated in 30 rural coloured volunteers (16 men, 14 women) working on an egg farm. Protein contributed approximately 11%, fat 31%, carbohydrate 58% (sucrose 21%) of energy intake. Daily cholesterol intake averaged 575 mg. In men, although not in women, cholesterol intake correlated negatively with serum cholesterol and low-density lipoprotein cholesterol levels, indicating that a high consumption of eggs in the study population did not prejudice lipid homeostasis. The population exhibited a high profile of coronary heart disease risk factors.

Cholesterol↗
PubMed1988

Vitamin B6 nutritional status in asthma: the effect of theophylline therapy on plasma pyridoxal-5'-phosphate and pyridoxal levels.

Plasma pyridoxal-5'-phosphate concentrations were significantly lower (p less than 0.001) in a group of 28 asthmatic women when compared to 33 controls. Plasma pyridoxal levels in the two groups were not different. Theophylline was administered to a group of 17 volunteers and resulted in large reductions in plasma pyridoxal-5'-phosphate levels, while plasma pyridoxal levels and urinary 4-pyridoxic acid excretion were unaffected by theophylline therapy. An in vitro study showed that theophylline did not interfere with the high performance liquid chromatography assay for pyridoxal-5'-phosphate, indicating that theophylline could affect liver metabolism of vitamin B6.

Adolescent↗
PubMed1987

Effect of different levels of oral pyridoxine supplementation on plasma pyridoxal-5'-phosphate and pyridoxal levels and urinary vitamin B-6 excretion.

Plasma pyridoxal-5'-phosphate and pyridoxal levels increased significantly (p less than 0.05) when single, oral bolus doses of pyridoxine were increased from 10 to 25 and from 25 to 50 mg in nine female volunteers. However, when the dose was increased to 100 mg, plasma pyridoxal-5'-phosphate levels did not differ significantly from those recorded after the 50 mg dose. Within 3 h plasma pyridoxal levels rose with a factor of 3.85 compared with the 50 mg dose but high pyridoxal levels were eliminated from the circulation. Renal clearance of pyridoxal remained a constant, low percentage (less than 2.0%) of each pyridoxine supplement in spite of the observed very high circulating pyridoxal levels. Pyridoxine supplementation is discussed in relation to circulating pyridoxal-5'-phosphate and pyridoxal availability for cellular metabolism.

Administration, Oral↗
PubMed1986

Depressed plasma pyridoxal-5'-phosphate levels in tobacco-smoking men.

Tobacco-smoking men (n = 106) showed considerably lower plasma pyridoxal-5'-phosphate levels (P less than 0.001) than non-smoking controls (n = 143). A previously reported inverse relationship between plasma pyridoxal-5'-phosphate levels and age is confirmed by using new and sensitive high-performance liquid chromatography methodology for pyridoxal-5'-phosphate determinations. Plasma pyridoxal levels were neither lower in tobacco-smoking men nor could any relationship between pyridoxal levels and age be demonstrated. Two major risk factors for coronary artery disease, tobacco-smoking and increasing age, are thus associated with lower plasma pyridoxal-5'-phosphate levels.

Adult↗
PubMed1986

Determination of urinary 4-pyridoxic acid levels as 4-pyridoxic acid lactone using high-performance liquid chromatography.

A high-performance liquid chromatography method for quantitation of urinary 4-pyridoxic acid excretion is presented. Urine samples were treated with HCl to form 4-pyridoxic acid lactone. Acid-treated urine samples were diluted and analyzed by cation-exchange chromatography involving post-column alkalinization and fluorescence detection. Absence of interfering fluorescent urinary compounds was demonstrated by analyzing urine samples without lactonization and rechromatography of aliquots of 4-pyridoxic acid lactone peaks employing reverse-phase chromatography. The method is suitable for determination of urinary 4-pyridoxic acid excretion in nutritional, metabolic, and pharmacokinetic studies.

Chromatography, High Pressure Liquid↗
PubMed1985

Stability of pyridoxal-5-phosphate semicarbazone: applications in plasma vitamin B6 analysis and population surveys of vitamin B6 nutritional status.

The determination of pyridoxal-5-phosphate (PLP) and pyridoxal (PL) in plasma requires the availability of dark room facilities, due to the photosensitivity of these vitamin B6 vitamers. The fact that the semicarbazone forms of PL and PLP are more strongly fluorescent than the underivatized B6 vitamers has been exploited in plasma analyses, but it was not previously realised that these semicarbazone forms are also very stable even under conditions that lead to rapid decomposition of free PL and PLP. The stabilisation of PLP and PL obtained in this manner is sufficient and fully adequate to meet the practical requirements of clinical field studies. We report a high-performance liquid chromatographic method for plasma PLP and PL determinations based on precolumn semicarbazone formation and fluorescence detection. The method is sensitive enough for quantitative plasma PLP determinations even in B6-deficient patients.

Chromatography, High Pressure Liquid↗