Nordic recommended dietary allowances for omega 3 and omega 6 fatty acids.
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Adult↗
Biomedical subjects
J I Pedersen
Publications and source records attributed to J I Pedersen.
Importance of peroxisomes in the formation of chenodeoxycholic acid in human liver. Metabolism of 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid in Zellweger syndrome.
Infantile Zellweger syndrome belongs to the group of peroxisomal disorders that lack peroxisomes. Both trihydroxycoprostanic acid (THCA), the precursor to cholic acid, and dihydroxycoprostanic acid (DHCA), the precursor to chenodeoxycholic acid, accumulate in this disease. In previous studies, we have shown that liver peroxisomes are required for the conversion of THCA into cholic acid both in vitro and in vivo by measuring a defective conversion in infants with Zellweger syndrome. In our present study, the conversion of DHCA into chenodeoxycholic acid has been measured in an infant with Zellweger syndrome to evaluate the importance of liver peroxisomes for the formation of chenodeoxycholic acid. Coprostanic acidemia was present from the second day of life with high levels of THCA and only trace amounts of DHCA. The conversion of i.v. administered [3H]DHCA into chenodeoxycholic acid was only 7% compared with the 80% conversion in an analogous study in an adult. There was, however, a rapid incorporation of 3H into biliary THCA and, after a lag phase, the 3H was incorporated into biliary cholic acid. After 72 h, 15% of [3H]DHCA was converted to cholic acid. The pool size of DHCA was 1.2 mg/m2 and the pool size of both cholic acid and chenodeoxycholic acid was markedly reduced. The renal excretion of cholic acid was more efficient than that of the less polar chenodeoxycholic acid. More polar metabolites of DHCA and THCA are formed in alternative metabolic pathways facilitating renal excretion of these toxic intermediates. We conclude that liver peroxisomes are essential for a normal conversion of DHCA into chenodeoxycholic acid.
Bile↗
Differential induction of peroxisomal oxidation of palmitic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid in rat liver.
The effect of feeding rats 20% partially hydrogenated marine oil (PHMO), 20% soybean oil, or clofibrate on the conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid to cholic acid was studied in light mitochondrial (L) fractions prepared from liver. 20% PHMO gave a doubling both of the specific and of the total activity of the cholic acid formation compared to those found in the L-fraction from animals given standard pellets. 20% soybean oil induced the specific and the total activity to a lesser extent, 1.4- and 1.2-fold, respectively. The specific and total activity of the peroxisomal beta-oxidation of palmitic acid were induced 2.4- and 2.7-fold, respectively, by PHMO feeding. Soybean oil gave a smaller increase, 2-fold, in both specific and total activity. Clofibrate, a known peroxisomal proliferator, induced the specific and total activity of the peroxisomal fatty acid beta-oxidation 5.2- and 5.7-fold, respectively, whereas the specific activity of the cholic acid formation remained unchanged compared to standard pellet feeding. The same pattern was found in the postnuclear supernatants (E-fractions), excluding the possibility that different treatments caused different distributions of organelles between the fractions. This differential induction of two similar peroxisomal reaction sequences suggests that at least two mechanisms for peroxisomal induction exist.
Acyl-CoA Oxidase↗
Uptake and degradation of vitamin D binding protein and vitamin D binding protein-actin complex in vivo in the rat.
We have labelled the rat vitamin D binding protein (DBP), DBP-actin and rat albumin with 125I-tyramine-cellobiose (125I-TC). In contrast with traditional 125I-labelling techniques where degraded radioactive metabolites are released into plasma, the 125I-TC moiety is trapped intracellularly in the tissues, where the degradation of the labelled proteins takes place. By using this labelling method, the catabolism of proteins can be studied in vivo. In this study we have used this labelling technique to compare the tissue uptake and degradation of DBP, DBP-actin and albumin in the rat. DBP-actin was cleared from plasma at a considerably faster rate than DBP. After intravenous injection of labelled DBP-actin complex, 48% of the radioactive dose was recovered in the liver after 30 min, compared with 14% when labelled DBP was administered. Only small amounts of DBP-actin complex were recovered in the kidneys. In contrast with the results obtained with DBP-actin complex, liver and kidneys contributed about equally in the uptake and degradation of DBP determined 24 h after the injection. When labelled DBP was compared with labelled albumin, the amount of radioactivity taken up by the liver and kidneys by 24 h after the injection was 2 and 5 times higher respectively. In conclusion, liver and kidneys are the major organs for catabolism of DBP in the rat. Furthermore, binding of actin to DBP enhances the clearance of DBP from circulation as well as its uptake by the liver.
Actins↗
Identification of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-enoic acid as an intermediate in the peroxisomal conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid to cholic acid.
In this study, we have identified a delta 24-unsaturated intermediate involved in the conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid to cholic acid by the peroxisomal fraction of rat liver. An accumulation of this intermediate was observed when NAD+ was omitted from the reaction mixture. The intermediate was isolated by reversed-phase high-pressure liquid chromatography and identified by combined gas-liquid chromatography-mass spectrometry. The peroxisomal fraction was able to catalyze the conversion of the delta 24-unsaturated intermediate to cholic acid in the presence of CoA, ATP, Mg2+ and NAD+. The identification of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic acid in cholic acid formation supports the proposed reaction mechanism in which the side-chain cleavage of C27-steroids is similar to that of peroxisomal beta-oxidation of fatty acids. This involves an FAD-dependent oxidase acting on 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoyl-CoA.
Adenosine Triphosphate↗
Nutrition and coronary heart disease.
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Adult↗
Reconstitution of C27-steroid 26-hydroxylase activity from bovine brain mitochondria.
We have previously demonstrated the presence of cytochrome P-450 in a soluble preparation of bovine brain mitochondria (Oftebro, H., Størmer, F.C., and Pedersen, J.I. (1979) J. Biol. Chem. 254, 4331). In the present work we show that this preparation, in the presence of NADPH, adrenodoxin and adrenodoxin reductase catalyzes omega-hydroxylation of a number of C27-steroids that are intermediates in bile acid biosynthesis. The rates of hydroxylation were 1-2 order of magnitudes lower than reported for similar preparations from rat and human liver. No significant activity was detected with cholesterol as substrate. The physiological significance of brain mitochondrial cytochrome P-450 is discussed.
Adrenodoxin↗
Effect of age, gonadectomy and hypophysectomy on mitochondrial hydroxylation of vitamin D3 (cholecalciferol) and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol in female and male rat liver.
In a previous study we found that liver mitochondrial side-chain hydroxylation of vitamin D3 (cholecalciferol) and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was higher in female than in male rats [Saarem & Pedersen (1987) Biochem. J. 247, 73-78]. The present paper describes the effects of age, gonadectomy and hypophysectomy on these activities. The sex difference became manifest above the age of 7 weeks. Ovariectomy and/or injection of oestradiol valerate had no effect on the hydroxylase activities in adult females. Castration increased, and subsequent testosterone treatment decreased, the hydroxylase activities in adult males. Hypophysectomy had no effect in females, but increased the hydroxylase activities in males. Testosterone treatment had no effect in hypophysectomized females or males. Injection of oestradiol valerate had no effect on the hydroxylase activities in hypophysectomized females. In hypophysectomized males this treatment had no effect on the vitamin D3 25-hydroxylase activity, but decreased the C27-steroid 27-hydroxylase activity in males. Microsomal 1 alpha-hydroxyvitamin D3 25-hydroxylase activity was lower in females than in males in all age groups. Castration or hypophysectomy decreased the activity in male rats. It is concluded that, in adult female rats, the mitochondrial side-chain hydroxylation of vitamin D3 and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol is independent of sex hormones. In males these activities are regulated by influence of sex hormones on the hypophysis, probably by the presence of androgens in the neonatal period. Different effects on the two hydroxylases indicate the presence of at least two different cytochromes P-450 in rat liver mitochondria.
Aging↗
Properties of guinea-pig kidney 25-hydroxyvitamin D3 1 alpha-hydroxylase assayed by isotope dilution-mass spectrometry.
1. A highly specific and accurate method based on isotope dilution-mass spectrometry was used for characterization of the renal 25-hydroxyvitamin D3 1 alpha-hydroxylase in untreated guinea pigs with a normal vitamin D status. In previous work, the properties of the enzyme had been determined in rachitic animals only. 2. With intact mitochondria, the reaction required the presence of citric acid-cycle intermediates. The uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone had an inhibitory effect on the isocitrate-supported reaction, indicating that energy-dependent transhydrogenation is of importance. Mitochondrial respiratory-chain inhibitors (cyanide, rotenone, antimycin A) had no effect on the hydroxylation. CO had an inhibitory effect, suggesting participation of a species of cytochrome P-450 in the reaction. A fraction solubilized from mitochondria by cholate became catalytically active in 1 alpha-hydroxylation of 25-hydroxyvitamin D3 after addition of ferredoxin and ferredoxin reductase. The isocitrate-supported reaction catalysed by crude mitochondria had an apparent Km of about 1 microM. 3. An atmosphere containing 50% O2 was found to be necessary for optimal activity. It is thus possible that O2 may be a limiting factor under normal conditions in vivo. 4. The results demonstrate that the mammalian renal 25-hydroxyvitamin D3 1 alpha-hydroxylase is a cytochrome P-450-dependent mixed-function oxidase with properties similar to those previously reported for the same enzyme system in chicken. The present assay and animal system seem to be suitable for further studies on the mechanism of regulation of the mammalian renal 25-hydroxyvitamin D3 1 alpha-hydroxylase under conditions when the vitamin D status is normal.
Animals↗
Assay and properties of 25-hydroxyvitamin D3 23-hydroxylase. Evidence that 23,25-dihydroxyvitamin D3 is a major metabolite in 1,25-dihydroxyvitamin D3-treated or fasted guinea pigs.
Incubation of 25-hydroxyvitamin D3 with kidney cortex mitochondria from 1,25-dihydroxyvitamin D3-treated guinea pigs resulted in the formation of 23,25-dihydroxyvitamin D3 as the major product. The identity of the product was verified by g.c.-m.s. and quantification was performed by h.p.l.c. The rates of the reaction were in the range 1.0-1.8 pmol/min per mg of mitochondrial protein (at 37 degrees C), which were 5-10 times the rates of formation of 24,25-dihydroxyvitamin D3. In mitochondrial preparations from untreated guinea pigs, the rate of 23-hydroxylation was below detection limit (0.02 pmol/min per mg of mitochondrial protein). Fasting the animals for 24 h induced the 23-hydroxylase almost as efficiently as treatment with 1,25-dihydroxyvitamin D3, with a concomitant depression of the 1 alpha-hydroxylase. The 23-hydroxylase reaction required oxidizable substrate, was decreased by low O2 partial pressures and inhibited by CO or the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone. It was stimulated by the respiratory-chain inhibitors rotenone, antimycin A and KCN. These results indicate that the guinea-pig renal mitochondrial 23-hydroxylase is a cytochrome P-450 and that the reducing equivalents are primarily supplied by NADPH via the energy-dependent transhydrogenase.
Animals↗
Subcellular localization of 3 alpha, 7 alpha-dihydroxy- and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoyl-coenzyme A ligase(s) in rat liver.
Liver peroxisomes from both rat and humans have previously been shown to contain enzymes that catalyze the oxidative cleavage of the C27-steroid side chain in the formation of bile acids. It has not been clear, however, whether the initial step, formation of the CoA-esters of the 5 beta-cholestanoic acids, also occurs in these organelles. In the present work the subcellular localization of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoyl-CoA (THCA-CoA) ligase (THCA-CoA synthetase) and of 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoyl-CoA (DHCA-CoA) ligase in rat liver has been investigated. Main subcellular fractions and peroxisome-rich density gradient fractions from rat liver were incubated with THCA or DHCA, CoA, ATP, and Mg2+. Formation of THCA-CoA and DHCA-CoA was determined after high pressure liquid chromatography of the incubation extracts. The microsomal fraction contained the highest specific (and also relative specific) activity both for the formation of THCA-CoA and DHCA-CoA. The rates of THCA-CoA formation were further increased from 124-159 nmol/mg.hr-1 in crude microsomal fractions to 184-220 nmol/mg.hr-1 when studied in purified rough endoplasmic reticulum fractions. Formation of THCA-CoA in peroxisomal fractions prepared in Nycodenz density gradients could be accounted for by a small contamination (3-7%) by microsomal protein. The distribution of THCA-CoA ligase was different from that of palmitoyl-CoA ligase that was found to be localized also to the peroxisomal fractions.
Animals↗
Clofibrate does not induce peroxisomal 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoyl coenzyme A oxidation in rat liver. Evidence that this reaction is catalyzed by an enzyme system different from that of peroxisomal acyl-coenzyme A oxidation.
The effect of clofibrate treatment of rats on the peroxisomal conversion in vitro of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid into cholic acid in liver fractions has been investigated. No increase in the activity was observed after clofibrate treatment. In contrast, peroxisomal palmitate oxidation and palmitoyl-CoA oxidase activity increased several fold. It is concluded that the enzyme system responsible for the oxidative cleavage of the steroid side chain in bile acid formation is different from the enzyme system involved in the peroxisomal beta-oxidation of long chain fatty acids.
Animals↗
An attempt to identify and describe a group of non-institutionalised elderly with the lowest nutrient score.
This report presents an attempt to identify the elderly with the least satisfactory diet (those with the 20% lowest total nutrient score (Group A)). Group A is compared with the elderly with the most satisfactory diet (those with the 20% highest total nutrient score (Group B)). The groups were compared according to demographical data, health problems, body mass index (BMI), social isolation and utilization of services. The sample, 201 women and 54 men, mean age 82 and 80 years, respectively, consisted of non-institutionalised elderly in Oslo. A food frequency interview method was used to collect information about diet. Other data were collected through interviews, observation and physical examinations. Group A had a higher percentage of women (87 vs 68%), were of higher age (83 vs 81 years), and a higher percentage had a BMI below 20 kg/m2 (36 vs 19%). The elderly in A, regardless of gender, had lower mobility function and were less often out of doors during the summer than those in B. No differences were seen in the percentages of those wearing dentures (81 vs 78%), living alone (83 vs 77%), duration of education (8.3 vs 8.4 years), and economic limitations on food purchases.
Aged↗
Dietary intakes and nutritional status of old people with dementia living at home in Oslo.
A nutritional study was carried out of 16 independent-living elderly (9 women, 7 men) suffering from dementia and a control group matched for sex and age. The study consisted of interview (with participants or relatives/home helps), a 3-d weighed dietary record and biochemical determinations of blood components. No significant difference in mean daily energy intake between demented elderly (women 7.2 +/- 2.0 MJ, men 8.6 +/- 1.2 MJ) and controls (women 6.9 +/- 0.7 MJ, men 9.4 +/- 2.0 MJ) was found. The women with dementia had lower dietary intakes of protein (P less than 0.05), thiamin (P less than 0.05) and vitamin C (P less than 0.01) than female controls. For both sexes in both groups the nutrients most lacking were vitamin D and thiamin. Dietary supplements were more frequently used among elderly with dementia (50 per cent) than among controls (13 per cent) (P less than 0.05). Except for vitamin D, supplements did not reduce the number of demented elderly with low intakes (less than two-thirds of the recommendations) because generally those in most need were non-users. The demented elderly had lower levels of haemoglobin and folic acid (blood and plasma) (P less than 0.05) but better thiamin status (alpha-transketolase) than controls (P less than 0.05). No difference in mean levels of protein, 25-hydroxyvitamin D, vitamin E, vitamin B12 in serum was found. Individuals with blood or serum levels of nutrients below reference values were more frequently found among the demented elderly than among controls. In the dementia group 2 individuals with low levels of 25-hydroxyvitamin D also had clinical evidence of osteomalacia.
Aged↗
High pressure liquid chromatography solvent systems for studies of bile acid biosynthesis.
Reversed phase high pressure liquid chromatography (HPLC) solvent systems have been developed for the separation of intermediates in the formation of bile acids and bile acid conjugates from cholesterol. Four different mobile phases (water-methanol, 10 mM acetate buffer (pH 4.37)-methanol, 30 mM trifluoroacetic acid (pH 2.9 with triethylamine)-methanol, and 50 mM potassium phosphate buffer (pH 7.0)-2-propanol) have been applied to obtain separation of all the main intermediates with use of the same reversed phase column (Zorbax ODS).
Bile Acids and Salts↗
Sex differences in the hydroxylation of cholecalciferol and of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol in rat liver.
The effect of sex hormones on hydroxylation of cholecalciferol ('vitamin D3') and of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol has been investigated in female- and male-rat livers. The mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities were respectively 4.6- and 2.7-fold higher in female- than in male-rat livers. The microsomal 1 alpha-hydroxycholecalciferol 25-hydroxylase was 2.8-fold higher in male- than in female-rat liver. No significant difference was found in the microsomal 25-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. Liver microsomes (microsomal fractions) from male, but not from female, rats also catalysed 1-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. Injection of testosterone into female rats decreased the mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities, but not to a statistically significant extent. Testosterone treatment had no effect on the microsomal hydroxylases in female-rat liver. Injection of oestradiol valerate to male rats resulted in increased activities of both mitochondrial hydroxylases to the same levels as those of control females, while the microsomal enzyme activities decreased. The present results indicate that sex hormones exert a regulatory control on the mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities.
Animals↗
Chain-shortening of prostaglandin F2 alpha by rat liver peroxisomes.
Liver peroxisomes were isolated from di(2-ethylhexyl)phthalate treated rats by isopycnic sucrose gradient centrifugation of a light mitochondrial fraction. Incubation of prostaglandin F2 alpha with purified peroxisomes resulted in conversion into a more polar product(s). In contrast, incubation with mitochondrial fractions and microsomal fractions under the same conditions did not result in any detectable conversion. The polar material obtained from a preparative incubation was purified by high performance liquid chromatography and characterized by radio-gas chromatography and gas chromatography-mass spectrometry. The structure of the polar compound was shown to be 5,7,11-trihydroxy-tetranorprost-9-enoic acid (tetranor-prostaglandin F1 alpha). Prostaglandin F2 alpha was thus chain-shortened by four carbon atoms.
Animals↗
Vitamin D status of two groups of elderly in Oslo: living in old people's homes and living in own homes.
Vitamin D status of two groups of elderly was determined by measuring serum concentrations of 25-hydroxyvitamin D3 (25-OHD), and dietary and supplemental vitamin D intake. Group A consisted of 35 women (mean age 86 years), and 21 men (mean age 80 years) living in 5 different homes for elderly. Group B consisted of free-living elderly, 24 women (mean age 76 years) and 7 men (mean age 79 years). There was no or little seasonal variation in serum 25-OHD concentrations in either group. Of those who did not use vitamin D supplements, 83% of the women and 77% of the men in group A, and 40% of the women and none of the men in group B had 25-OHD concentrations below 20 ng/ml in the winter serum samples. Of the 49 individuals who used supplements, only 2 had values below 20 ng/ml. In the institutionalized elderly, 14-15 micrograms vitamin D per day as supplement was associated with a mean increase in 25-OHD concentration in winter serum samples of 25 ng/ml. Dietary intakes of vitamin D were low for both groups, especially for the women (less than 3 micrograms). It is concluded that elderly Norwegians, in particular those living in institutions, ought to improve their vitamin D status by increasing their exposure to sunshine and by including more oily fish in their diet. If this is difficult to achieve, vitamin D supplement (10 micrograms/day) should be used.
Aged↗