Efflux system for pyridoxine in Schizosaccharomyces pombe.
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Pyridoxine-charged Schizosaccharomyces pombe released pyridoxine rapidly at 30 degrees C: very low amounts of three other B6 vitamers were also released. The rate of efflux was temperature-dependent. The initial rate of efflux was dependent on the concentration of pyridoxine in the cells: the rate was almost zero at lower than 0.02 mM and became saturated at higher than 0.2 mM. Na+, sodium azide, and dinitrophenol increased the rate in both the presence and absence of D-glucose. Mg++, thiamine, and menadione inhibited the efflux. The intracellular concentration of ATP did not significantly affect the efflux rate. The system may be dependent on a membrane potential of the yeast cells. It was found that the fission yeast cells have a gate or carrier system for efflux of pyridoxine, which was distinct from that in Saccharomyces cerevisiae. (+info)
Homocystinuria due to cystathionine synthase deficiency. Studies of nitrogen balance and sulfur excretion.
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Apparent nitrogen balances and urinary sulfur excretions were determined for normal subjects, seven cystathionine synthase-deficient patients, and a single cystathioninuric patient on semisynthetic diets containing low-adequate amounts of methionine and very low amounts of methionine and very low amounts (12 mg daily, or less) of cystine. The amounts of supplemental cystine required to prevent abnormally high nitrogen or sulfur losses were determined. The five cystathionine synthase-deficient patients who had low residual activities of this enzyme detected in fibroblast and/or liver extracts did not lose more nitrogen or sulfur on diets virtually devoid of cystine than did the normal subjects. These results suggest that the widely expressed opinion that cystine is an essential amino acid for cystathionine syntase-deficient patients requires modification. Residual enzyme activity of only a few percent of normal may obviate such a cystine requirement. These results are compatible with, and lend support to, the working hypothesis which states that the pyridoxine response in cystathionine synthase-deficient patients is mediated by an increase in the residual activity of the affected enzyme. (+info)
Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans.
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BACKGROUND: In population studies, high intakes of coffee are associated with raised concentrations of plasma homocysteine, a predictor of risk of cardiovascular disease. Chlorogenic acid is a major polyphenol in coffee; coffee drinkers consume up to 1 g chlorogenic acid/d. OBJECTIVE: We studied whether chlorogenic acid affects plasma total homocysteine concentrations in humans. For comparison we also studied the effects of black tea rich in polyphenols and of quercetin-3-rutinoside, a major flavonol in tea and apples. DESIGN: In this crossover study, 20 healthy men and women ingested 2 g (5.5 mmol) chlorogenic acid, 4 g black tea solids containing approximately 4.3 mmol polyphenols and comparable to approximately 2 L strong black tea, 440 mg (0.7 mmol) quercetin-3-rutinoside, or a placebo daily. Each subject received each of the 4 treatments for 7 d, in random order. RESULTS: Total homocysteine in plasma collected 4-5 h after supplement intake was 12% (1.2 micromol/L; 95% CI: 0.6, 1.7) higher after chlorogenic acid and 11% (1.1 micromol/L; 95% CI: 0.6, 1.5) higher after black tea than after placebo. Total homocysteine in fasting plasma collected 20 h after supplement intake was 4% (0.4 micromol/L; 95% CI: 0.0, 0.8) higher after chlorogenic acid and 5% (0.5 micromol/L; 95% CI: 0.0, 0.9) higher after black tea than after placebo. Quercetin-3-rutinoside did not significantly affect homocysteine concentrations. CONCLUSIONS: Chlorogenic acid, a compound in coffee, and black tea raise total homocysteine concentrations in plasma. Chlorogenic acid could be partly responsible for the higher homocysteine concentrations observed in coffee drinkers. Whether these effects on homocysteine influence cardiovascular disease risk remains to be established. (+info)
Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort.
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BACKGROUND: Established determinants of fasting total homocysteine (tHcy) concentration include folate and vitamin B-12 status, serum creatinine concentration, and renal function. OBJECTIVE: Our objective was to examine the relation between known and suspected determinants of fasting plasma tHcy in a population-based cohort. DESIGN: We examined the relations between fasting plasma tHcy concentrations and nutritional and other health factors in 1960 men and women, aged 28-82 y, from the fifth examination cycle of the Framingham Offspring Study between 1991 and 1994, before the implementation of folic acid fortification. RESULTS: Geometric mean tHcy was 11% higher in men than in women and 23% higher in persons aged > or = 65 y than in persons aged < 45 y (P < 0.001). tHcy was associated with plasma folate, vitamin B-12, and pyridoxal phosphate (P for trend < 0.001). Dietary folate, vitamin B-6, and riboflavin were associated with tHcy among non-supplement users (P for trend < 0.01). The tHcy concentrations of persons who used vitamin B supplements were 18% lower than those of persons who did not (P < 0.001). tHcy was positively associated with alcohol intake (P for trend = 0.004), caffeine intake (P for trend < 0.001), serum creatinine (P for trend < 0.001), number of cigarettes smoked (P for trend < 0.001), and antihypertensive medication use (P < 0.001). CONCLUSIONS: Our study confirmed, in a population-based setting, the importance of the known determinants of fasting tHcy and suggested that other dietary and lifestyle factors, including vitamin B-6, riboflavin, alcohol, and caffeine intakes as well as smoking and hypertension, influence circulating tHcy concentrations. (+info)
Analysis of the pdx-1 (snz-1/sno-1) region of the Neurospora crassa genome: correlation of pyridoxine-requiring phenotypes with mutations in two structural genes.
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We report the analysis of a 36-kbp region of the Neurospora crassa genome, which contains homologs of two closely linked stationary phase genes, SNZ1 and SNO1, from Saccharomyces cerevisiae. Homologs of SNZ1 encode extremely highly conserved proteins that have been implicated in pyridoxine (vitamin B6) metabolism in the filamentous fungi Cercospora nicotianae and in Aspergillus nidulans. In N. crassa, SNZ and SNO homologs map to the region occupied by pdx-1 (pyridoxine requiring), a gene that has been known for several decades, but which was not sequenced previously. In this study, pyridoxine-requiring mutants of N. crassa were found to possess mutations that disrupt conserved regions in either the SNZ or SNO homolog. Previously, nearly all of these mutants were classified as pdx-1. However, one mutant with a disrupted SNO homolog was at one time designated pdx-2. It now appears appropriate to reserve the pdx-1 designation for the N. crassa SNZ homolog and pdx-2 for the SNO homolog. We further report annotation of the entire 36,030-bp region, which contains at least 12 protein coding genes, supporting a previous conclusion of high gene densities (12,000-13,000 total genes) for N. crassa. Among genes in this region other than SNZ and SNO homologs, there was no evidence of shared function. Four of the genes in this region appear to have been lost from the S. cerevisiae lineage. (+info)
Effect of diet and 677 C-->T 5, 10-methylenetetrahydrofolate reductase genotypes on plasma homocyst(e)ine concentrations in slovak adolescent population.
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The objective of this study was to evaluate the effect of diet and 677 C-->T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene on plasma homocyst(e)ine concentrations in an adolescent population (113 males, age: 14.2+/-2.4 years; 202 females, age: 14.9+/-2.1 years) from a region characterized by high cardiovascular mortality. Homocyst(e)ine levels did not differ between males and females (9.4+/-3.5 and 8.9+/-3.1 micromol/l, respectively). The homozygosity for the 677 C-->T MTHFR mutation was found in 4.6 % of subjects. No differences in homocyst(e)ine levels were found between MTHFR genotypes. Analysis of the diet composition which was performed on a 24-hour daily recall basis and a food frequency questionnaire showed a low daily intake of vitamin B6 (males: 1.13 mg/66% RDA; females: 0.92 mg/61% RDA). Daily folic acid intake was 0.21 g/105% RDA in males and 0.23 g/115% RDA in females. The results of our study show that the high homocyst(e)ine levels in the adolescent population were not affected by the 677 C-->T MTHFR mutation. We conclude that an insufficient dietary intake of vitamin B6 and folic acid is responsible for this finding. This is in accord with the recommendation that the dietary allowances for folate should be reset to the originally prescribed levels of 0.4 g/day which should be sufficient to control the homocysteine levels. (+info)
Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model.
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Although hyperhomocysteinemia (HHcy) is a well-known risk factor for the development of cardiovascular disease, the underlying molecular mechanisms are not fully elucidated. Here we show that induction of HHcy in apoE-null mice by a diet enriched in methionine but depleted in folate and vitamins B6 and B12 increased atherosclerotic lesion area and complexity, and enhanced expression of receptor for advanced glycation end products (RAGE), VCAM-1, tissue factor, and MMP-9 in the vasculature. These homocysteine-mediated (HC-mediated) effects were significantly suppressed, in parallel with decreased levels of plasma HC, upon dietary supplementation with folate and vitamins B6/B12. These findings implicate HHcy in atherosclerotic plaque progression and stability, and they suggest that dietary enrichment in vitamins essential for the metabolism of HC may impart protective effects in the vasculature. (+info)
Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete.
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BACKGROUND: Current data suggest that physiologic doses of vitamin B-6 have no significant homocysteine-lowering effect. It is possible that an effect of vitamin B-6 was missed in previous trials because of a much greater effect of folic acid, vitamin B-12, or both. OBJECTIVE: The aim of this study was to investigate the effect of low-dose vitamin B-6 supplementation on fasting total homocysteine (tHcy) concentrations in healthy elderly persons who were made replete with folate and riboflavin. DESIGN: Twenty-two healthy elderly persons aged 63-80 y were supplemented with a low dose of vitamin B-6 (1.6 mg/d) for 12 wk in a randomized, double-blind, placebo-controlled trial after repletion with folic acid (400 microg/d for 6 wk) and riboflavin (1.6 mg/d for 18 wk); none of the subjects had a vitamin B-12 deficiency. RESULTS: Folic acid supplementation lowered fasting tHcy by 19.6% (P < 0.001). After folic acid supplementation, baseline tHcy concentrations ranged from 6.22 to 23.52 micromol/L and 10 subjects had suboptimal vitamin B-6 status (plasma pyridoxal-P < 20 nmol/L). Two-way analysis of variance showed that the significant improvement in vitamin B-6 status in response to vitamin B-6 supplementation (on the basis of both pyridoxal-P: and the erythrocyte aspartate aminotransferase activation coefficient) was reflected in a significant reduction in plasma tHcy of 7.5%. CONCLUSIONS: Low-dose vitamin B-6 effectively lowers fasting plasma tHcy in healthy subjects who are both folate and riboflavin replete. This suggests that any program aimed at the treatment or prevention of hyperhomocysteinemia should include vitamin B-6 supplementation. (+info)