Biomedical subjects

J I Pedersen

Publications and source records attributed to J I Pedersen.

At least 37 records · Page 2Linked to original sources

PubMed1998

Effect on plasma lipids and lipoproteins of replacing partially hydrogenated fish oil with vegetable fat in margarine.

We have compared the effects on lipoproteins and haemostatic variables of two hard margarines with similar functional properties, one traditional margarine containing partially hydrogenated fish oil (PHFO), and one experimental margarine based on vegetable oil (VO). Both were all-purpose cooking margarines with nearly identical functional properties. Trans fatty acids from PHFO in the traditional margarine were replaced mostly by saturated, monounsaturated and trans fatty acids of vegetable origin in the new formulation. Both test margarines contained approximately the same amount of cis polyunsaturated fatty acids. Sixteen female normolipidaemic students consumed each diet with the two test margarines for 14 d in random order (crossover design). The amount of fat was 31% energy in the PHFO diet and 32% energy in the VO diet. The test margarines provided approximately 26% energy in both diets. In the PHFO diet 7.8% of the energy was derived from trans fatty acids and 9.2% from saturated fatty acids (12:0, 14:0 and 16:0) while in the VO diet, 1.1% energy was derived from trans fatty acids and 13.3% from saturated fatty acids (12:0, 14:0 and 16:0). The natural content of cholesterol in PHFO was deliberately not balanced by addition of cholesterol to the VO diet, thus the PHFO diet contained 215 mg and the VO diet 86 mg cholesterol per 8.5 MJ. LDL-cholesterol concentration was 19% higher in subjects on the PHFO diet compared with the VO diet (P < 0.01). The ratio LDL-cholesterol:HDL-cholesterol was 12.6% higher in subjects on the PHFO diet compared with the VO diet (P < 0.01). The level of apolipoprotein (apo)A-I was 6% lower in subjects on the PHFO diet compared with the VO diet (P < 0.01). The ratio apoB:apoA-I was 10.4% higher in subjects on the PHFO diet than on the VO diet (P < 0.01). There were no significant differences in total cholesterol, HDL-cholesterol, triacylglycerols, apoB, lipoprotein(a) and haemostatic variables between the diets. Our results demonstrate that PHFO, with its unfavourable effects on plasma lipids, can be replaced by vegetable oils in margarine without appreciable loss of functional properties but with significant improvement in the effects on plasma lipoproteins.

Adult↗

PubMed1997

Molecular cloning and expression of cDNA encoding 3alpha,7alpha,12alpha-trihydroxy-5beta-chole stanoyl-CoA oxidase from rabbit liver.

The steroid side chain cleavage in bile acid formation is catalyzed by liver peroxisomal enzymes (Pedersen, J. I. and Gustafsson, J. (1980) FEBS Lett. 121, 345-348; Kase, F., Björkhem, I., and Pedersen, J. I. (1983) J. Lipid Res. 24, 1560-1567). We here describe the cloning and sequencing of a cDNA coding the first of these enzymes, a 3alpha,7alpha,12alpha-trihydroxy-5beta-choles tanoyl-CoA oxidase (THCA-CoA oxidase) from rabbit liver peroxisomes. After tryptic digestion of purified protein in a polyacrylamide gel, five peptides were isolated and sequenced. Using two oligonucleotides deduced from the amino acid sequence data, two overlappping clones were isolated from a rabbit liver cDNA library, which together made up a unique cDNA sequence of 2139 base pairs. It contained an open reading frame of 2046 base pairs encoding a protein of 681 amino acids with a molecular mass of 76,209 daltons. All five peptides could be localized within the sequence. Transfection of COS cells with the coding part of the cDNA resulted in a significant expression of THCA-CoA oxidase activity. We were not able to demonstrate 3alpha, 7alpha-dihydroxy-5beta-cholestanoyl-CoA oxidase activity under the same conditions. The obtained sequence showed 73.6% similarity with a proposed rat THCA-CoA oxidase and 81% similarity with a recently reported human branched chain acyl-CoA oxidase, indicating that these three proteins represent the same enzyme. The similarity with rat palmitoyl-CoA oxidase was 41.8%. The C-terminal tripeptide of the protein was SNL, a previously undescribed variant of the main class of peroxisomal targeting signals. Northern blot analysis revealed that the gene is transcribed in liver and kidney, and the major mRNA fraction had a size of approximately 2.6 kilobase pairs.

Amino Acid Sequence↗

PubMed1997

Dietary factors and the incidence of hip fracture in middle-aged Norwegians. A prospective study.

Dietary data from a prospective study were used to relate factors influencing calcium balance (estimates of dietary calcium intake, protein intake from nondairy animal sources (meat, fish, and eggs), and coffee consumption) to the incidence of hip fracture. During the years 1977-1983, women and men born between 1925 and 1940 and living in one of three Norwegian counties were invited to a cardiovascular screening that included a dietary survey. The attendance rate at screening was 91.1%, and 90.7% of these persons (19,752 women and 20,035 men) filled in and returned a semiquantitative dietary questionnaire. This cohort was followed for an average of 11.4 years (range, 0.01-13.8 years) with respect to hip fracture, defined as cervical or trochanteric fracture. During follow-up, 213 hip fractures were identified, excluding fractures associated with high-energy trauma and metastatic bone disease. There was no clear association between calcium intake or nondairy animal protein intake and hip fracture in this cohort. However, an elevated risk of fracture was found in women with a high intake of protein from nondairy animal sources in the presence of low calcium intake (relative risk = 1.96 (95% confidence interval 1.09-3.56) for the highest quarter of nondairy protein intake and the lowest quarter of calcium intake vs. the three lower quarters of protein intake and the three higher quarters of calcium intake). Women who drank nine or more cups of coffee per day also had an increased risk of fracture, while there was no association between coffee consumption and hip fracture in men. Although these findings do not necessarily imply causal relations, they suggest the presence of risk factors for hip fracture that act through a negative calcium balance in this population.

Adult↗

PubMed1996

[Risk factors of femoral neck fractures in Oslo].

In this matched case-control study from Oslo, risk factors for hip fracture were assessed in elderly non-institutionalized women and men. 246 hip fracture patients admitted to two hospitals in the course of one year were matched by sex and age to controls living in the catchment area of the hospitals We found increased risk of hip fracture in lean persons, in persons with self-reported weight loss because of poor appetite, and in persons with low food intake. One third of the hip fracture patients ate less than three slices of bread per day and one fourth ate less than three meals a day. We found no relation between calcium intake and hip fracture, whereas higher risk of fracture was suggested in persons with low vitamin D intake. Hip fracture was also associated with low levels of physical activity, low hand grip strength, smoking, low level of education, and frequent admissions to hospital prior to the study.

Aged↗

PubMed1996

Substrate stereospecificity in oxidation of (25S)-3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoyl-CoA by peroxisomal trihydroxy-5 beta-cholestanoyl-CoA oxidase.

Partly purified 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoyl-CoA oxidase from rabbit liver peroxisomes was found to convert the 25S- but not the 25R diastereoisomer of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-27-oyl-CoA into (24E)-3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-en-27-oic acid. In the presence of a peroxisomal THCA-CoA racemase, however, also the 25R isomer was oxidized. Since the mitochondrial steroid-27-hydroxylase, responsible for formation of THCA, is 25R specific a racemase seems to be obligatory for formation of cholic acid by the normal peroxisomal-dependent pathway.

Acyl Coenzyme A↗

PubMed1996

Effects of partially hydrogenated fish oil, partially hydrogenated soybean oil, and butter on hemostatic variables in men.

We have compared the effects of partially hydrogenated fish oil (PHFO diet), partially hydrogenated soybean oil (PHSO diet), and butterfat (butter diet) on fibrinolytic and coagulation variables in 31 young men. The three test margarines, which contributed 78% of total fat in the diets, contained 70% butterfat, PHSO, or PHFO, each with 30% of soybean oil. Fat provided approximately 35% of energy, and the content of trans-fatty acids was 0.9%, 8.5%, and 8.0% of energy in the butter diet, PHSO diet, and PHFO diet, respectively. All diets contained 420 mg cholesterol per 10 megajoules per day. All subjects consumed all three test diets for 3 weeks, in a random order (crossover design). The PHSO diet resulted in higher levels of plasminogen activator inhibitor type 1 antigen and plasminogen activator inhibitor type 1 activity than the two other test diets. Fibrinogen increased on the butter diet compared with the PHFO diet. No significant differences in the levels of factor VII, fibrinopeptide A, D-dimer, tissue plasminogen activator or beta-thromboglobulin were observed between the three test diets. The PHFO and the PHSO diets have previously been shown to result in higher levels of Lp(a) compared with the butter diet. The present findings indicate that PHSO has unfavorable antifibrinolytic effects relative to PHFO and butter and that butter may be procoagulant relative to PHFO. More controlled studies are needed to assess definitely the impact of different hydrogenated fats on risk of coronary heart disease.

Adult↗

PubMed1996

Effects of partially hydrogenated fish oil, partially hydrogenated soybean oil and butter on the susceptibility of low density lipoprotein to oxidative modification in men.

OBJECTIVE: To study the effect of partially hydrogenated fish oil (PHFO-diet), partially hydrogenated soybean oil (PHSO-diet) and butterfat (butter-diet) on the susceptibility of low density lipoprotein (LDL) to in vitro oxidative modification. DESIGN: A strictly controlled, randomized, single-blind dietary study with cross-over design. SUBJECTS: Thirty-three healthy men aged from 21 to 46 years entered the study; 29 men completed the study. INTERVENTIONS: Fat provided approximately 35% of the energy intake in all three test diets, and the content of trans-fatty acids was 8.0, 8.5 and 0.9% of energy in the PHFO-, PHSO- and butter-diets, respectively. The subjects consumed all three test diets each during three weeks, in a single-blind, random order. LDL isolated from the participants given the three different diets was subjected to Cu(2+)-induced oxidation. RESULTS: No significant differences were seen on either conjugated dienes, lipid peroxides, uptake by macrophages or relative electrophoretic mobility of LDL. Vitamin E level in serum from subjects on the PHFO-diet was significantly higher compared to the two other diets. Furthermore, no significant differences were found in the composition of the LDL particle between the three diet groups. CONCLUSIONS: Our results indicate that consumption of trans-fatty acids does not alter the susceptibility of LDL to oxidative modification.

Adult↗

PubMed1995

Risk factors for hip fracture in a high incidence area: a case-control study from Oslo, Norway.

The aim of this population-based matched case-control study was to evaluate the effect of risk factors for hip fracture in Oslo, Norway, which has some of the highest incidence rates ever reported. The study population comprised all non-institutionalized persons 50 years or older living in the catchment area of two Oslo hospitals, and cases were 246 patients admitted for hip fracture during a 1-year period. The controls were randomly selected from the study population, matched 1:1 for age and sex. Hip fracture was associated with lean body stature, smoking, low grip strength and decreased levels of physical activity, and inversely with length of education. In addition, hip fracture was inversely related to indicators of total food intake (number of meals per day, frequency of dinners, and slices of bread per day). A relation between hip fracture and low vitamin D intake was also suggested, whereas no association with dietary calcium intake was found. Finally, increased risk of fracture was seen in persons reporting two or more hospital admissions in the previous 2 years, and in those reporting weight reduction due to poor appetite during the previous year. In conclusion, the risk factor pattern for hip fracture was much the same in the elderly population of Oslo as previously described in other populations with a lower incidence of fracture. This study also indicates a relation between hip fracture and low food intake.

Aged↗

PubMed1995

[Vitamin D and osteoporosis].

Vitamin D constitutes a complex endocrine-regulated system, and is both a prohormone for the endogenous synthesis of the active hormone, calcitriol, and a vitamin which may be administered to supply the organism's requirements. No single test or investigation is available for the demonstration of vitamin D deficiency. Both vitamin D intake and ability to synthesise vitamin D decrease with increasing age, and particularly the elderly in institutionalised care are at risk of developing vitamin D deficiency. Iceland excepted, mean daily vitamin D consumption in the Nordic countries is less then 5 micrograms; and in approximately 10-25 per cent of the population, daily intake is less than 2.5 micrograms which is insufficient to maintain an adequate serum calcidiol concentration in individuals unexposed to sunlight. The recommended daily intake of 5 micrograms, currently adopted in the Nordic countries, may be too low-an intake of 10 micrograms is probably necessary to satisfy requirements in the elderly.

Adrenal Cortex Hormones↗

PubMed1995

Effects of partially hydrogenated fish oil, partially hydrogenated soybean oil, and butter on serum lipoproteins and Lp[a] in men.

We have compared the effects of partially hydrogenated fish oil (PHFO-diet), partially hydrogenated soybean oil (PHSO-diet), and butterfat (butter-diet) on serum lipids and lipoprotein[a] in 31 young men. The three test margarines, which contributed 78% of total fat in the diets, were produced from 70% of butterfat, PHSO, or PHFO, each with 30% of soybean oil. Fat provided about 35% of energy, and trans fatty acids 0.9%, 8.5%, and 8.0% of energy in the butter-, the PHSO-, and the PHFO-diet, respectively. Dietary cholesterol was balanced by the addition of dried egg powder to the PHSO- and the butter-diet; thus all diets contained 420 mg dietary cholesterol per 10 MJ per day. The subjects consumed all three test diets for 19-21 days in a random order (crossover design). The serum levels of total and LDL-cholesterol were significantly elevated on the PHFO-diet (mean values 5.42 and 3.94 mmol/L, respectively) compared to the PHSO-diet (5.11 and 3.58 mmol/L, respectively) but not different from those on the butter-diet (5.32 and 3.81 mmol/L, respectively). LDL-cholesterol was significantly reduced on the PHSO-diet compared to the butter-diet. The level of HDL-cholesterol was significantly lower on the PHFO-diet (0.98 mmol/L) when compared to the butter-diet (1.05 mmol/L) and with border-line significance compared to the PHSO-diet (1.05 mmol/L). The ratio of LDL- to HDL-cholesterol was significantly higher on the PHFO-diet (4.20) when compared to both other test diets (3.85 and 3.65, respectively). No significant differences in triglyceride values were observed. Lp[a] increased and apoA-I decreased significantly after consumption of both the PHSO-diet and the PHFO-diet, compared to the butter-diet. In conclusion, our results indicate that consumption of PHFO may unfavorably affect lipid risk indicators for coronary heart disease at least to the same extent as butterfat. To what extent the observed effects are due to the content of monoene trans, diene trans, or to the long chain saturated fatty acids in PHFO remains to be elucidated.

Adult↗

PubMed1995

Diet and vitamin D status among pregnant Pakistani women in Oslo.

OBJECTIVES: In the present study the diet and the nutritional status of pregnant Pakistani immigrant women have been compared with a group of Norwegian women. DESIGN: A cross-sectional survey of women in the 18th week of pregnancy. SETTING: Women referred to routine ultrasound examination at Aker and Ullevål Hospitals in Norway. SUBJECTS: All (58) healthy women of Pakistani origin referred from October of 1991 to January of 1992 were included, of whom 38 (66%) participated. Forty-five Norwegian women were randomly included in the same period and 38 (84%) of these women participated. RESULTS: The serum levels of 25-hydroxyvitamin D3 were significantly lower in the Pakistanis compared with the Norwegians (median 19 nmol/l vs 55 nmol/l, P < 0.001) and 83% of the Pakistani women had 25-hydroxyvitamin D3 levels below the reference value (< 30 nmol/l). The Pakistanis had higher levels of serum parathyroid hormone (median 2.6 vs 1.6 pmol/l, P < 0.001). The Pakistanis also had a lower dietary intake of vitamin D than that of the Norwegians (median 2.2 vs 3.3 micrograms/day, P < 0.05), and a lower total intake, including supplements (median 2.9 vs 7.0 micrograms/day, P < 0.001). Among the Pakistanis a correlation was found between the dietary intake of margarine, the main source of vitamin D in the diet, and the concentration of 25-hydroxyvitamin D3 in serum, r = 0.48 (P = 0.01). In general, the Pakistanis avoided any direct sunshine exposure, and no relation between outdoor activity and serum level of 25-hydroxyvitamin D3 was found. The Pakistani women had a lower intake of calcium than the Norwegians (median 793 vs 1134 mg/day, P < 0.001). CONCLUSION: This study has shown that Pakistani women living in Oslo are at great risk of developing vitamin D deficiency during pregnancy. The main reasons for this are avoidance of sun exposure, a low dietary intake of vitamin D, and no or little use of supplementation.

Adult↗

PubMed1995

Potentiating effects of clofibric acid on the differentiation of HL-60 human promyelocytic leukemia cells induced by retinoids.

Retinoids induce granulocytic differentiation of HL-60 human promyelocytic leukemia cells. In this study we demonstrate that clofibric acid, a well known peroxisome proliferator in rodent, augments the differentiation caused by 0.01 microM and 0.1 microM all-trans retinoic acid, and by 0.3 and 3 microM all-trans retinol. Clofibric acid alone has only marginal effects on the myeloid differentiation, whereas clofibric acid together with the glucocorticoid analogue dexamethasone gives a larger effect. Exposure of cultures to retinoid inhibits the growth of the cells, but despite the increased differentiation addition of clofibric acid to the medium does not further inhibit the growth. HL-60 cells express the nuclear receptor NUCI, a human receptor related to the peroxisome proliferator activated receptor (PPAR).

Cell Differentiation↗

PubMed1993

The effect of retinoids and clofibric acid on the peroxisomal oxidation of palmitic acid and of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid in rat and rabbit hepatocytes.

The effects of retinoids and the peroxisome proliferator clofibric acid on peroxisomal enzyme pathways were studied in hepatocytes from both rat and rabbit. Retinoic acid and retinol increased the activity of acyl-CoA oxidase in rabbit hepatocytes around 60% and around 30% in rat hepatocytes. Exposure to clofibric acid caused an increase in acyl-CoA oxidase activity of 115% in rat hepatocytes and of 40% in rabbit hepatocytes, indicating that rabbit is less sensitive to peroxisome proliferator than rat. Simultaneous exposure to clofibric acid and retinoids did not act additatively or synergistically. Both rabbit and rat hepatocytes expressed mRNA for the peroxisome proliferator activated receptor, (PPAR), although the transcript in rabbit was slightly smaller compared to that expressed in rat hepatocytes. The effect of retinoic acid in 7800 C1 Morris rat hepatoma cells, a cell line known to have an inducible peroxisomal beta-oxidation of fatty acids, was only slight with an increase of the acyl-CoA oxidase activity of 25% compared with control cells. As for clofibric acid, which gave a 2-fold induction of the acyl-CoA oxidase activity, the effect of retinoic acid was potentiated by dexamethasone. These cells also expressed mRNA for PPAR, with the same size as that found in rat hepatocytes. The oxidation of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA), an intermediate in bile acid formation, in rat hepatocytes increased 110% by clofibric acid and around 80% by retinoic acid. In rabbit hepatocytes, clofibric acid increased the oxidation rate 75% and retinoic acid 100%. The results presented here show similarities in the effects of retinoids and clofibric acid on the acyl-CoA oxidase activity and the oxidation rate of THCA, since they increase these two peroxisomal activities in hepatocytes in vitro. A decrease in both these enzyme activities occurs during cultivation time in untreated primary hepatocyte cultures. The present data may therefore either be explained by an increased expression or an induced stability of the enzymes involved.

Animals↗

PubMed1993

Peroxisomal oxidation of the steroid side chain in bile acid formation.

An overview of the formation of the primary bile acids is given with special emphasis on the final steps, ie the oxidative cleavage of the steroid side chain. The enzymes involved in this oxidation are localized to liver peroxisomes and catalyze conversion of di- and trihydroxy-5 beta-cholestanoic acid into chenodeoxycholic and cholic acid, respectively. Two of the intermediates in cholic acid formation have been identified, viz 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-enoic acid and 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestanoic acid. The corresponding hypothetical 24-oxo compound has not been finally identified. The first enzyme in the reaction sequence, trihydroxy-5 beta-cholestanoyl-CoA oxidase, has recently been partly purified and shown to be separate from the corresponding peroxisomal acyl-CoA oxidase. The subsequent enzymes, the trifunctional enzyme and the thiolase, are most certainly shared in the oxidation of both fatty acids and cholestanoic acids. In several peroxisomal disorders bile acid intermediates with an uncleaved steroid side chain accumulate, thus clearly demonstrating the importance of liver peroxisomes in the normal formation of bile acids in man.

Animals↗

PubMed1993

Human hepatoblastoma cells (HepG2) and rat hepatoma cells are defective in important enzyme activities in the oxidation of the C27 steroid side chain in bile acid formation.

We have examined the ability of HepG2 human hepatoblastoma cells and 7800 C1 Morris rat hepatoma cells to convert 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) and 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA) to cholic acid and chenodeoxycholic acid, respectively. Cell extracts from both these cell lines could neither form cholic acid from THCA nor from the activated form, THCA-CoA. This suggests that both cell lines are defective in two enzyme activities involved in the pathway, the microsomal THCA-CoA ligase and the peroxisomal THCA-CoA oxidase. Furthermore, we show that the subsequent enzymes are active in the conversion to bile acids, because the product of the THCA-CoA oxidase, 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-enoyl-coenzyme A (delta 24-THCA-CoA) or delta 24-THCA in the presence of THCA-CoA ligase, are converted to cholic acid by both cell lines. HepG2 cells were able to slowly form chenodeoxycholic acid and cholic acid from 5 beta-cholestane-3 alpha, 7 alpha-diol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, respectively, in 24- and 96-h incubations. The rate of cholic acid formation was lower than the rate for chenodeoxycholic acid and there was a clear accumulation of THCA. 7800 C1 Morris cells had no ability to form cholic acid or chenodeoxycholic acid after 96 h incubation. We conclude that these two cell lines have defects in two enzyme activities involved in the peroxisomal oxidation in bile acid formation, the microsomal THCA-CoA ligase and the peroxisomal THCA-CoA oxidase.

Animals↗

PubMed1992

Dietary intake in a group of independent-living old people in Oslo.

Dietary intake (24-h recall), dietary supplementation practice and relative weight (BMI) were investigated in a random sample of 257 independent-living elderly persons above 75 years. The proportion of energy from fat was unfavorably high among women (41.7%), while diet nutrient density was similar for men and women. Mean intakes of vitamin D, thiamin and iron were below recommended levels. Use of a dietary supplement was more common among women (66%) than men (48%). Average daily energy intakes of 6.3 +/- 2.1 MJ in women and 7.3 +/- 2.2 MJ in men were just below the lower limit of the reference interval. Overweight was uncommon, while 14% of the women and 4% of the men had BMI below 18.5 kg/m2; 2% had a BMI below 16. We conclude that low energy intake is the major reason for potential malnutrition in this group of elderly persons; up to 10% may be at risk for energy deficiency, while 2% were chronic energy deficient.

Aged↗

PubMed1991

Metabolic aspects of peroxisomal beta-oxidation.

In the course of the last decade peroxisomal beta-oxidation has emerged as a metabolic process indispensable to normal physiology. Peroxisomes beta-oxidize fatty acids, dicarboxylic acids, prostaglandins and various fatty acid analogues. Other compounds possessing an alkyl-group of six to eight carbon atoms (many substituted fatty acids) are initially omega-oxidized in endoplasmic reticulum. The resulting carboxyalkyl-groups are subsequently chain-shortened by beta-oxidation in peroxisomes. Peroxisomal beta-oxidation is therefore, in contrast to mitochondrial beta-oxidation, characterized by a very broad substrate-specificity. Acyl-CoA oxidases initiate the cycle of beta-oxidation of acyl-CoA esters. The next steps involve the bi(tri)functional enzyme, which possesses active sites for enoyl-CoA hydratase-, beta-hydroxyacyl-CoA dehydrogenase- and for delta 2, delta 5 enoyl-CoA isomerase activity. The beta-oxidation sequence is completed by a beta-ketoacyl-CoA thiolase. The peroxisomes also contain a 2,4-dienoyl-CoA reductase, which is required for beta-oxidation of unsaturated fatty acids. The peroxisomal beta-hydroxyacyl-CoA epimerase activity is due to the combined action of two enoyl-CoA hydratases. (For a recent review of the enzymology of beta-oxidation enzymes see Ref. 225.) The broad specificity of peroxisomal beta-oxidation is in part due to the presence of at least two acyl-CoA oxidases, one of which, the trihydroxy-5 beta-cholestanoyl-CoA (THCA-CoA) oxidase, is responsible for the initial dehydrogenation of the omega-oxidized cholesterol side-chain, initially hydroxylated in mitochondria. Shortening of this side-chain results in formation of bile acids and of propionyl-CoA. In relation to its mitochondrial counterpart, peroxisomal beta-oxidation in rat liver is characterized by a high extent of induction following exposure of rats to a variety of amphipathic compounds possessing a carboxylic-, or sulphonic acid group. In rats some high fat diets cause induction of peroxisomal fatty acid beta-oxidation and of trihydroxy-5 beta-cholestanoyl-CoA oxidase. Induction involves increased rates of synthesis of the appropriate mRNA molecules. Increased half-lives of mRNA- and enzyme molecules may also be involved. Recent findings of the involvement of a member of the steroid hormone receptor superfamily during induction, suggest that induction of peroxisomal beta-oxidation represents another regulatory phenomenon controlled by nuclear receptor proteins. This will likely be an area of intense future research. Chain-shortening of fatty acids, rather than their complete beta-oxidation, is the prominent feature of peroxisomal beta-oxidation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Peroxisomal fatty acid beta-oxidation in HepG2 cells.

HepG2 cells, originally derived from a human hepatoblastoma, contain peroxisomes which could be separated from mitochondria and other subcellular organelles by density gradient centrifugation. To determine whether this cell line was a suitable model for human peroxisomal fatty acid beta-oxidation, we investigated the ability of these cells to catabolize very-long-chain fatty acids (VLCFA). HepG2 cell homogenates or digitonin-disrupted cells oxidized both long chain fatty acids and VLCFA, although at somewhat lower rates than human liver homogenates. beta-Oxidation of VLCFA was observed in both peroxisomes and mitochondria of HepG2 cells. Peroxisomal beta-oxidation was independent of carnitine, insensitive to antimycin A and rotenone, and not blocked by an inhibitor of carnitine palmitoyl transferase I. HepG2 peroxisomes contained immunoreactive acyl-CoA oxidase, the first enzyme unique to the peroxisomal beta-oxidation pathway. In addition, HepG2 peroxisomes contained VLCFA-CoA synthetase activity. These results suggest that HepG2 may be a useful model system for the study of human peroxisomal metabolic processes, including beta-oxidation of fatty acids.

Acyl-CoA Oxidase↗