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Biomedical subjects

N Iritani

Publications and source records attributed to N Iritani.

At least 73 records · Page 4Linked to original sources

Selectivities of 1-acylglycerophosphorylcholine acyltransferase and acyl-CoA synthetase for n-3 polyunsaturated fatty acids in platelets and liver microsomes.

1- Acylglycerophosphorylcholine acyltransferase in platelets and liver microsomes showed a selectivity for polyunsaturated fatty acids. The acyl-donor specificity of the enzyme for 1- acylglycerophosphorylcholine and also 1- acylglycerophosphorylethanolamine was high for n-3 eicosapentaenoyl -CoA and docosahexaenoyl -CoA, and highest for arachidonyl-CoA. Further, the enzyme activity was higher for n-6 eicosatrienoyl -CoA than for n-3 and n-9 eicosatrienoyl -CoAs. It appears that the acyltransferase has a predominant selectivity for n-6 series, but the selectivity is not limited to this series. Acyl-CoA synthetase of liver microsomes and platelets also exhibited a high selectivity for n-3 polyunsaturated fatty acids as well as n-6. In platelets, the acyl-CoA synthetase activity preferential to polyunsaturated fatty acids (n-3 and n-6) was found by competitive aspects of incorporation, in addition to the activity preferential to palmitic acid. In any case, it is suggested that n-3 polyunsaturated fatty acids are easily incorporated into platelet and liver phospholipids.

1-Acylglycerophosphocholine O-Acyltransferase↗

Comparative study of lipogenic enzymes in several vertebrates.

The liver lipogenic enzymes are compared among rats, chickens, frogs and fish. Although the apparent Km values of glucose-6-phosphate dehydrogenase for glucose-6-phosphate are not much different among all the species, those of malic enzyme for malate are much higher in chickens and fish than in rats and frogs. Glucose-6-phosphate dehydrogenase showed very high activities compared with malic enzyme in fish liver, and malic enzyme showed high activities in chicken liver. Although the apparent Km values of acetyl-CoA carboxylase and fatty acid synthetase for substrates are in the same range among all the animals, the activity of acetyl-CoA carboxylase seems to be extremely low in fish and frog livers, and that of fatty acid synthetase is low in frog livers only. In addition, the apparent Km values of alpha-glycerophosphate acyltransferase of fish liver are very high, and the enzyme activity appears to be extremely low compared to the others. Therefore, the enzymes at the first steps of both fatty acid and glycerolipid syntheses of poikilothermos animals appear to be very low. On the other hand, the Ouchterlony double-diffusion patterns showed that the lipogenic enzymes of chickens, frogs and fish are immunologically different from those of rats, with the exception of acetyl-CoA carboxylase in chickens. Therefore, it is suggested that the fatty acid and glycerolipid forming systems of poikilothermos animals are quite different from those of homoiothermos and the lipogenesis is very low in poikilothermos.

Acetates↗

Physiological impairment in linoleic acid deficiency of rats and the effect of n-3 polyunsaturated fatty acids.

Some impairments related to membrane function were found in linoleic acid-deficient rats and the effects of fish oil feeding were investigated. In linoleic acid-deficient rats, glucose transport into erythrocytes was decreased. The concentrations of plasma free fatty acids were significantly reduced in the animals. Further, epinephrine-stimulated lipase was remarkably less sensitive to epinephrine in the deficient rat than in the corn oil-fed control rat. However, these impairments were relieved by fish oil feeding. Therefore, the impairments may be ascribed to the decrease of arachidonic acid as a polyunsaturated fatty acid in membrane phospholipids, since n-3 polyunsaturated fatty acids appear to take the place of arachidonic acid.

Adipose Tissue↗

Effect of insulin-treatment on age-dependent decrease of lipogenic enzyme induction.

The effects of insulin-treatment on induction of liver lipogenic enzymes by a fat-free diet were investigated in 1-, 2- and 9-month-old rats. The magnitudes of the induction of the enzymes were very high in 1-month-old rats and decreased with aging (Iritani, N., Fukuda, H. and Fukuda, E. (1981) Biochim. Biophys. Acta 665, 636). The induction of lipogenic enzymes was not affected by insulin injection in young rats. In 9-month-old rats, however, although the maximal magnitudes of the induction were not affected by the insulin injection, the lag periods of the induction were shortened. The lipogenic enzyme induction in 9-month-olds did not correlate with plasma insulin level but paralleled changes in the insulin binding capacities to liver plasma membranes and adipocytes. The results suggest that insulin binding is implicated in age-dependent decrease of lipogenic enzyme induction, and support our previous report (Iritani, N., Fukuda, H., Tashiro, S. and Ikeda, Y. (1982) J. Biochem. 92, 569).

Acetyl-CoA Carboxylase↗

Induction of rat liver malic enzyme messenger RNA activity by insulin and by fructose.

The effects of insulin treatment and fructose feeding on malic enzyme [EC 1.1.1.40] mRNA in liver of diabetic rats were investigated. A high fructose diet, even without insulin treatment, increased the mRNA activity, much more than a high starch diet, but to a lesser extent than insulin treatment. The increase of malic enzyme activity was approximately comparable to the change in mRNA activity, but occurred 12 hr and 30 hr after the increase of mRNA in the fructose-fed rats with and without insulin treatment, respectively. Thus, insulin and fructose appear to induce malic enzyme primarily by increasing the activity of translatable mRNA.

Animals↗

Effects of high-fructose diet on lipogenic enzymes and their substrate and effector levels in diabetic rats.

When rats adapted to a stock diet were fed on various high-carbohydrate diets, the hepatic activities of glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase were more greatly increased by fructose than by any other carbohydrate. Even in the diabetic state, the enzyme activities were somewhat increased by fructose feeding. After feeding on the diets for 9 days, the hepatic concentrations of intermediates of carbohydrate metabolism were generally lower in the diabetics than in the normals. Moreover, in both the normal and diabetic rats, the concentrations of fructose-1-phosphate, acetyl-CoA, citrate and malate were increased by fructose as were the enzyme activities. These results suggest that the metabolic pathway of fructose is predominant with respect to that of glucose and consequently lipogenesis may be able to be increased in the fructose-fed rats.

Acetyl Coenzyme A↗

Activation of catalase and other enzymes by corn oil intake.

The effects of linoleic and intake on catalase and other enzymes were investigated by feeding 0, 1, 5 or 10% corn oil diet to rats previously fed a fat-free diet. Rats fed more than 1% corn oil for 2 weeks showed significant increases of glutathione peroxidase and superoxide dismutase in liver cytosol when compared to the controls fed no corn oil. Peroxisomal catalase activity especially was increased. The catalase activity was markedly increased also by ethyl linoleate intubation. Thus, it was demonstrated that the peroxide elimination mechanisms were activated by linoleic acid intake. The elevation of peroxide elimination mechanisms were activated by linoleic acid intake. The elevation of peroxisomal catalase by linoleic acid intake might be related to the hypolipidemic effect, similar to the possible relation between peroxisome induction and the hypolipidemic effect of many hypolipidemic compounds, which has been reported.

Animals↗

Age-dependent alterations of insulin binding to hepatic plasma membranes, erythrocytes and adipocytes in rat.

The insulin binding to hepatic plasma membranes, erythrocytes and adipocytes of 1-, 2-, and 9-month-old rats was measured by using [125I]insulin. When rats were fed a fat-free diet, the capacities of the insulin bindings significantly decreased with aging, whereas the dissociation constants were not altered. The capacities of 9-month-old rats were decreased to about half those of 1-month-old rats for plasma membranes, and about one-third for erythrocytes and adipocytes. On the other hand, the plasma insulin levels tended to be high with increasing age at 9-10 a.m., while the levels were even more elevated at 8-9 p.m. and not altered by aging. The insulin binding capacities were increased by feeding the fat-free diet to rats adapted to a stock diet and the increases were reduced with aging. The insulin binding capacities correlated well with the magnitudes of induction of lipogenic enzymes as reported previously [Iritani, N., Fukuda, H., & Fukuda, E. (1981) Biochim. Biophys. Acta 665, 636]. Therefore, it is suggested that insulin binding is implicated in age-dependent alterations of lipogenic enzyme induction.

Adipose Tissue↗

Cholesterol and bile acid metabolism in hypertensive arteriolipidosis-prone rats (ALR).

Bile flow and biliary bile acids were analyzed in arteriolipidosis-prone rats (ALR), the hypertensive model for lipidemic arterial lesions with reactive hypercholesterolemia and compared to those in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Bile flow and bile acid secretion decreased in the order of WKY, SHR and ALR. When labelled cholesterol was given intraperitoneally, the biliary radioactivity secretion was significantly slow in ALR in comparison with that in WKY. The decay of radioactive cholesterol in serum after the injection was also delayed in ALR. Our data suggest that the abnormality in bile flow, biliary bile acid secretion and/or cholesterol turnover to bile acids may be pathogenically related to reactive hypercholesterolemia noted in the ALR.

Animals↗

Immunological studies of lipogenic enzymes during aging.

The effects of aging on enzyme qualities of glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase were investigated. The Ouchterlony double-diffusion pattern showed that the enzymes from livers of rats of different ages are immunologically similar to each other. In addition, immunochemical titration demonstrated that the changes in the levels of activity of rats of different age are accompanied by proportionate changes in the quantity of the enzyme protein. The Kms of the enzymes for substrates were not altered by aging. It is suggested that the age-dependent impairments of the enzyme induction (Iritani, N., Fukuda, H., and Fukuda, E. (1981) Biochim. Biophys. Acta, 665, 639) can be ascribed to decreases in the rise of enzyme protein quantities.

Acetyl-CoA Carboxylase↗

Competitive incorporation of dietary omega-3 and omega-6 polyunsaturated fatty acids into the tissue phospholipids in rats.

The incorporation of dietary omega-3 and omega-6 polyunsaturated fatty acids into the phospholipids of the liver, plasma and heart was studied by feeding rats with diets of increasing amounts of fish oil and/or corn oil up to 5% each for 2 weeks. Irrespective of the sources and amounts of dietary fat, total unsaturated fatty acids were 53-60% of phospholipid fatty acids in liver and plasma, and were 70-73% in heart. In all the animals either given or not given unsaturated fatty acid in diet, the sums of polyunsaturated fatty acids with more than three double bonds such as arachidonic acid, omega-3 polyunsaturated fatty acids and endogenous omega-9 eicosatrienoic acid were always 31-35, 18-20 and 30-38% in liver, plasma and heart, respectively. Dietary omega-3 unsaturated fatty acids and arachidonic acid appeared to be comparably incorporated into the phospholipids and substituted for each other in the phospholipids. These data may suggest that omega-3 polyunsaturated fatty acids compete with arachidonic acid for the C-2 position of the phospholipids.

Animals↗

Age-dependent modifications of lipogenic enzymes.

When 1-, 2- and 9-month-old rats previously adapted to a commercial stock diet were fed a fat-free diet (induction) and also when the process was reversed (repression), the turnovers of lipogenic enzymes in liver were measured by following time courses for the change of the enzyme activities. The magnitudes of the induction of glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase were very high in 1-month-old rats and then decreased with aging. In the induction phase, the rates of synthesis of the enzymes were markedly decreased with increasing age as compared with the rate constants of degradation. The age-dependent alterations were not shown so much in the repression phase as in the induction phase. It is suggested that the age-dependent impairment in induction may be due to some alterations in the enzyme-forming system.

Acetyl-CoA Carboxylase↗

The binding of cholic acid to protein in rat serum and liver.

After the intraperitoneal administration of radioactive cholic acid to rats, the binding of the cholic acid to protein was immunologically investigated. The serum and liver cytosol were separately incubated with antiligandin or antialbumin immunoglobulin and then subjected to sucrose density gradient centrifugation. The sedimentation behavior of the radioactivity, endogenous bile acids, glutathione S-transferase activity of ligandin and protein provided evidence that cholic acid is bound to both ligandin and albumin in liver, and mostly to albumin in serum. However, little, if any, cholic acid seems to be bound to protein in bile. These results suggest that ligandin and albumin are the major physiological carriers of bile acid.

Animals↗

Mechanism of hypercholesterolemia in arteriolipidosis-prone rats (ALR).

The cholesterol metabolism of a newly established model for atherogenesis, named arteriolipidosis-prone rats (ALR), selected from spontaneously hypertensive rats (SHR), was investigated in comparison with a substrain of SHR (B) (nonarteriolipidosis-prone rats) and the normotensive control. Wistar-Kyoto (WK) rats. Serum cholesterol of ALR was significantly lower than that of WK. Uptake of labelled serum cholesterol by the isolated liver cells at 37 degrees C was higher in ALR than in WK. The data for SHR (B) fell in between these two. On the other hand, on feeding a cholesterol diet, serum cholesterol increased in the order WK, SHR (B) and ALR, with the highest being ALR. The absorption of cholesterol in ALR was about twice as great as in WK and SHR (B).

Animals↗

Identification of shellfish fatty acids and their effects on lipogenic enzymes.

The fatty acids which are common to and characteristic of shellfish, were identified by mass spectrometry and NMR spectral analyses as being: octadecatetraenoioc acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid. When the fatty acids isolated by high performance liquid chromatography were separately intubated into rats, hepatic glucose-6-phosphate dehydrogenase (EC 1.1.1.49), malic enzyme (EC 1.1.1.40) and acetyl-CoA carboxylase (EC 6.4.1.2) were reduced more effectively as compared with linoleic acid intubation. These enzymes were reduced most markedly by eicosapentaenoic acid-intubation. The fatty acids seem to be effective components in reduction of triacylglycerol and lipogenic enzyme levels in rats fed on shellfish.

Acetyl-CoA Carboxylase↗

Effect of oxidized oil on lipogenic enzymes.

Male Wistar rats were fed for 4 wk on diets containing 2% oxidized corn oil. Liver tissue was then studied to determine the effect of feeding peroxidized oil on lipogenic enzymes. Although substances which reacted with thiobarbituric acid increased in liver microsomes and mitochondria with increasing peroxide values of the dietary corn oil fed, the activities of glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase in liver were unchanged. However, when rats were fed for 2 wk on diets containing 10% fat, of which 0.5, 5 or 10% was unoxidized corn oil and the remainder was hydrogenated beef tallow filler, the lipogenic enzyme activities and also the liver triglyceride levels were observed to decrease with increasing amounts of dietary corn oil. Therefore, although a synthetic diet containing corn oil was easy to oxidize spontaneously, the reductions of lipogenic enzymes in rats fed the diet would not have been caused by lipid peroxides but by unsaturated fatty acids themselves.

Acetyl-CoA Carboxylase↗

Effect of corn oil feeding on lipid peroxidation in rats.

Three groups of male rats were maintained on 10% fat diets containing 0.5, 5 or 10% corn oil or olive oil with 80--400 mg DL-alpha-tocopherol per kilogram. After 4 weeks on such regimens, TBA (thiobarbituric acid) values in serum, liver mitochondria and microsomes, and adipose tissue increased with rising amounts of dietary corn oil. TBA values in rats fed the 10% corn oil diet were reduced with the increase of dietary tocopherol but were still higher than the corresponding values of the 10% olive oil and 0.5% corn oil groups. When the liver microsomes were incubated with Fe3+-ADP and NADPH, the relative chemiluminescence emission in the visible region with the peroxidative cleavage of endogenous lipid was higher in the 5 and 10% corn oil groups than in the 0.5% group. On the other hand, when oxidized corn oil was given orally to rats with thoracic lymph fistula, TBA-reacting substances were recovered in thoracic lymph, but iodometric peroxide was undetectable. Therefore, TBA-reacting substances in rats fed the corn oil diets could have originated from the oxidative product of linoleic acid metabolism and also from the diet.

Adipose Tissue↗