Methylmalonic acid and coenzyme A concentrations in the livers of pair-fed vitamin B 12-deficient and vitamin B 12-treated sheep.
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ABSTRACT:
SUBMITTER: Smith RM
PROVIDER: S-EPMC1187774 | biostudies-other | 1969 May
REPOSITORIES: biostudies-other
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Project description:BackgroundElevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine β-synthase (CBS).ObjectivesWe investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength.MethodsWe measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and <210 nmol/L; pyridoxal-5'-phosphate; vitamin B-12 continuously and ≥258 pmol/L; and folate. The outcomes of interest included areal and volumetric BMD, measured by DXA and quantitative computed tomography (QCT), respectively. We evaluated associations between the bone measures and interactions of single nucleotide polymorphism with a B vitamin or biomarker in Framingham participants (n = 4310 for DXA and n = 3127 for QCT). For analysis of DXA, we validated the association results in the B-PROOF cohort (n = 1072). Bonferroni-corrected locus-wide significant thresholds were defined to account for multiple testing.ResultsThe interactions between rs2274976 and vitamin B-12 and rs34671784 and MMA <210 nmol/L were associated with lumbar spine BMD, and the interaction between rs6586281 and vitamin B-12 ≥258 pmol/L was associated with femoral neck BMD. For QCT-derived traits, 62 interactions between genetic variants and B vitamins and biomarkers were identified.ConclusionsSome genetic variants in the 1-carbon methylation pathway modify the association of B vitamin and biomarker concentrations with bone density and strength. These interactions require further replication and functional validation for a mechanistic understanding of the role of the 1-carbon metabolism pathway on BMD and risks of fracture.
| S-EPMC8326042 | biostudies-literature
Project description:BackgroundNo consensus exists about which cutoff point should be applied for serum vitamin B-12 (SB-12) concentrations to define vitamin B-12 status in population-based research.ObjectiveThe study's aim was to identify whether a change point exists at which the relation between plasma methylmalonic acid (MMA) and SB-12 changes slope to differentiate between inadequate and adequate vitamin B-12 status by using various statistical models.DesignWe used data on adults (≥19 y; n = 12,683) from NHANES 1999-2004-a nationally representative, cross-sectional survey. We evaluated 6 piece-wise polynomial and exponential decay models that used different control levels for known covariates.ResultsThe MMA-defined change point for SB-12 varied depending on the statistical model used. A linear-splines model was determined to best fit the data, as determined by the approximate permutation test; 3 slopes relating SB-12 and MMA and resulting in 2 change points and 3 subgroups were shown. The first group (SB-12 <126 pmol/L) was small and had the highest MMA concentration (median: 281 nmol/L; 95% CI: 245, 366 nmol/L; n = 157, 1.2%); many in this group could be considered at high risk of severe deficiency because combined abnormalities of MMA and homocysteine were very frequent and the concentrations themselves were significantly higher. The highest SB-12 group (SB-12 >287 pmol/L; n = 8569, 67.6%) likely had adequate vitamin B-12 status (median MMA: 120 nmol/L; 95% CI: 119, 125 nmol/L). The vitamin B-12 status of the sizable intermediate group (n = 3957, 33%) was difficult to interpret.ConclusionsThe 3 distinct slopes for the relation between SB-12 and MMA challenges the conventional use of one cutoff point for classifying vitamin B-12 status. In epidemiologic research, the use of one cutoff point would fail to separate the small, severely deficient group from the intermediate group that has neither normal nor clearly deficient vitamin B-12 concentrations (ie, unknown vitamin B-12 status). This intermediate group requires further characterization.
| S-EPMC3712554 | biostudies-literature
Project description:The size of the deoxyribonucleoside triphosphate pools of vitamin B-12-deficient cells of Euglena gracilis, and of vitamin B-12-deficient cells repleted with the vitamin, were measured. We found that the pools were very small, if they exist at all, in deficient cells but expand rapidly with the addition of the vitamin. The sizes of the pools decrease when DNA synthesis is completed, and are very small when the cells begin to divide.
| S-EPMC1163771 | biostudies-other
Project description:In vitamin B-12 (cobalamin) deficiency the metabolism of propionyl-CoA and methylmalonyl-CoA are inhibited secondarily to decreased L-methylmalonyl-CoA mutase activity. Production of acylcarnitines provides a mechanism for removing acyl groups and liberating CoA under conditions of impaired acyl-CoA utilization. Carnitine metabolism was studied in the vitamin B-12-deficient rat to define the relationship between alterations in acylcarnitine generation and the development of methylmalonic aciduria. Urinary excretion of methylmalonic acid was increased 200-fold in vitamin B-12-deficient rats as compared with controls. Urinary acylcarnitine excretion was increased in the vitamin B-12-deficient animals by 70%. This increase in urinary acylcarnitine excretion correlated with the degree of metabolic impairment as measured by the urinary methylmalonic acid elimination. Urinary propionylcarnitine excretion averaged 11 nmol/day in control rats and 120 nmol/day in the vitamin B-12-deficient group. The fraction of total carnitine present as short-chain acylcarnitines in the plasma and liver of vitamin B-12-deficient rats was increased as compared with controls. When the rats were fasted for 48 h, relative or absolute increases were seen in the urine, plasma, liver and skeletal-muscle acylcarnitine content of the vitamin B-12-deficient rats as compared with controls. Thus vitamin B-12 deficiency was associated with a redistribution of carnitine towards acylcarnitines. Propionylcarnitine was a significant constituent of the acylcarnitine pool in the vitamin B-12-deficient animals. The changes in carnitine metabolism were consistent with the changes in CoA metabolism known to occur with vitamin B-12 deficiency. The vitamin B-12-deficient rat provides a model system for studying carnitine metabolism in the methylmalonic acidurias.
| S-EPMC1135203 | biostudies-other
Project description:Analysis of livers from 74-day old male rats fed vitamin A sufficient or vitamin A deficient diet for 53 days. Either 10ug or 2ug of total RNA used in standard Affymetrix protocol
2007-11-01 | E-GEOD-1600 | biostudies-arrayexpress
Project description:1. The effect of the administration of vitamin B(12) and biotin on the metabolic pattern of vitamin B(12) in biotin-deficient rats was studied. 2. No significant changes in the absorption and excretion of orally administered [(58)Co]vitamin B(12) were noted either in vitamin B(12)-treated and or in biotin-fed rats. A significant decrease of the uptake of orally given [(58)Co]vitamin B(12) was observed in the liver and kidneys of biotin-treated rats, whereas an increase of uptake in the kidneys of vitamin B(12)-treated rats was noted as compared with biotin-deficient animals. 3. No significant difference in the excretion of radioactivity was noted between biotin deficient and biotin-fed rats when [(58)Co]vitamin B(12) was administered by injection. A small decrease was observed in vitamin B(12)-treated rats. The retention of injected [(58)Co]vitamin B(12) by major organs of biotin-treated rats was lower than that of biotin-deficient rats. A lower content of [(58)Co]vitamin B(12) was also detected in the organs, with the exception of the kidneys, of vitamin B(12)-treated rats. 4. These results are discussed in terms of an interrelationship between biotin and vitamin B(12).
| S-EPMC1206903 | biostudies-other
Project description:1. Metabolism of folate was studied in six ewes in an advanced state of vitamin B(12) deficiency as judged by voluntary food intake and in their pair-fed controls receiving vitamin B(12). A group of four animals that were maintained throughout the experiment at pasture was also studied. 2. After 34-40 weeks on the cobalt-deficient diet urinary excretion of formiminoglutamate by four deficient animals was about 3.2mmol/day and this was not significantly decreased by injection of three of them with about 4.5mug of [2-(14)C]folate/kg body weight per day for 5 days. Three days after the last injection retention of [2-(14)C]folate by the livers of the deficient animals (5.5% of the dose) was lower than that of their pair-fed controls (26% of the dose) but there was no evidence of net retention of injected folate in the livers of either group. Urinary excretion of (14)C indicated that renal clearance of folate may have been impaired in very severe vitamin B(12) deficiency. 3. As estimated by microbiological assays total folates in the livers of animals at pasture (12.9mug/g) included about 24% of 5-methyltetrahydrofolate as compared with about 72% of a total of 12.5mug/g in three further ewes fed on a stock diet of wheaten hay-chaff and lucerne-chaff. Liver folates of vitamin B(12)-deficient animals (0.5mug/g) included about 88% of 5-methyltetrahydrofolate as compared with about 51% of a total of 5.2mug/g in pair-fed animals treated with vitamin B(12). 4. Chromatography of liver folates of the pair-fed animals permitted quantitative estimates of the pteroylglutamates present. The results showed that the vitamin B(12)-deficient livers were more severely depleted of tetrahydrofolates and formyltetrahydrofolates than of methyltetrahydrofolates and that as the deficiency developed they were more severely depleted of the higher polyglutamates than of the monoglutamate within each of these classes. Results from animals injected with [2-(14)C]folate indicated an impairment of the exchange between pteroylmonoglutamates and pteroylpolyglutamates in the livers of deficient animals. 5. In vitamin B(12)-deficient animals with food intakes below 200g/day some of the liver folates were not completely reduced and some degradation of pteroylpolyglutamates was detected. The latter condition may have been associated with fatty liver. 6. The results are discussed in relation to current theories of vitamin B(12)-folate interactions.
| S-EPMC1165953 | biostudies-other
Project description:Relationships between increased adiposity and fat-soluble vitamin storage and metabolism are poorly understood. To examine these associations, 6% or 21% dietary fat was fed to rats for 11 weeks and tissue vitamin A storage determined. Two levels of supplemental vitamin A were administered. At the end of the tenth week, 3,4-didehydroretinol (DR) was administered orally, and its kinetics were followed for 1 week in serum and tissues. Model-based compartmental analysis was applied to these data. Kidney total retinol (R) concentrations were elevated in rats fed 6% compared with 21% dietary fat (n = 24/group). The fractional transfer coefficient (FTC) describing the movement of tracer from plasma to extravascular stores was two times higher in the 6% compared with the 21% fat group. Consistent with the elevated renal R in 6% fat fed rats, there was a 2-fold increase in the FTC representing tracer distribution from plasma to kidney in the 6% compared with 21% fat group. Taken together with a fat main effect on renal vitamin A, our data support the evidence that faster turnover of kidney R may help set the mechanism governing vitamin A tissue distribution during deficiency. Rats fed 21% versus 6% dietary fat conserved hepatic R more efficiently.
| S-EPMC2656663 | biostudies-literature
Project description:pre- and post-treatment sample pair Keywords: time-course
2003-04-21 | GSE220 | GEO
Project description:pre- and post-treatment sample pair Keywords: time-course
2003-04-21 | GSE242 | GEO