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Biomedical subjects

R R Brenner

Publications and source records attributed to R R Brenner.

At least 91 records · Page 5Linked to original sources

Daily variations of the biosynthesis and composition of fatty acids in rats fed on complete and fat-free diets.

This report describes the daily changes in fatty acid composition and fatty acid desaturation in rats feeding on a complete diet and a fat-free diet successively. Rats on a complete diet showed a good homeostasis in the percentage of fatty acid in plasma, with a possible palmitic acid rhythm, but the fat-free diet initiated an essential fatty acid-deficient pattern in a few hours. The light-dark period in animals feeding on a complete diet motivates a feeding rhythm that causes changes in linoleic and arachidonic acids in the whole liver and microsomes that are related to delta 6 and delta 5 desaturase activities. The patterns of delta 6 and delta 5 desaturase changes were different. Linoleic acid intake during the dark periods (complete diet feeding) caused a decrease of delta 6 desaturase activity and the activation of delta 5 desaturation that led to an increase of arachidonic acid biosynthesis. The feeding of a fat-free diet eliminated the rhythm observed in linoleic and arachidonic acid composition in the liver and changed the desaturase rhythms. The delta 9 desaturase activity in the liver also showed a daily rhythm in the complete-diet period that disappeared with the change to a fat-free diet, while the activity increased markedly. A negative correlation existed between the percentage of linoleic acid in the liver and the delta 9 desaturase activity. However, no correlation was found between delta 9 desaturase activity and the percentage of 16:1 and 18:1 in the complete-diet period.

Adipose Tissue↗

Effect of different amino acid diets on delta 5, delta 6 and delta 9 desaturases.

A high-protein diet with 45% calories from casein increased delta 6 desaturase activity in rat-liver microsomes. High-protein diets with 45% calories from a synthetic mixture of amino acids in the same proportion as casein decreased the delta 9 desaturase, slightly increased the delta 5 desaturase and greatly increased delta 6 desaturase activities compared with a high-carbohydrate diet. The elimination of phenylalanine and tyrosine from the synthetic mixtures of amino acids increased the delta 6 desaturase activity. Massive amounts of phenylalanine or tyrosine in the diet inhibited delta 6 desaturase activity. Tyrosine and phenylalanine may, by conversion to tyrosine, decrease the activity of the delta 6 desaturase.

Amino Acids↗

Effect of fatty acid deficiency on microsomal membrane fluidity and cooperativity of the UDP-glucuronyltransferase.

The effect of fat deprivation on microsomal membrane fluidity of guinea-pig livers and the kinetic cooperativity of UDP-glucuronyl transferase towards its natural substrate, the UDP-glucuronic acid, were studied. Fat deprivation in the diet of weanling guinea-pigs evoked a typical essential fatty-acid-deficient pattern in the composition of the microsomal membrane. The unsaturated:saturated fatty acid ratio progressively declined in the membrane during the 21-day period tested. This decline determined a gradual increase in the fluorescence anisotropy (rs) of the membrane labeled with diphenylhexatriene and the apparent microviscosity of the lipid bilayer calculated from these values increased from 1.1 to 1.8 poise. In addition, when the infinitely slow decaying fluorescence anisotropy ((r infinity), which is proportional to the square of the lipid order parameter, was calculated from rs data, a significant increase in these parameters was also obtained. Furthermore, this decrease of the double bond index:saturated acid ratio of the membrane was associated with a parallel increase in Hill coefficients of the UDP-glucuronyl transferase that gradually lost the negative homotropic effect and cooperativity of UDP-glucuronic acid. The Hill coefficient varied from 0.39 to 0.98 during the 21-day period studied. Our observations indicate on one side that changes in the fat composition of the diet are accompanied by modifications in the lipid composition and fluidity of the microsomal membrane, and the apparent cooperativity of the enzyme. On the other side, they suggest that the evaluation of Hill coefficients of UDP-glucuronyl transferase might be used as a sensitive test to investigate conformational changes in the microsomal membrane of the liver.

Animals↗

Effect of dietary fatty acids on delta 5 desaturase activity and biosynthesis of arachidonic acid in rat liver microsomes.

The effect of different fatty acids supplemented to a fat-free diet on the activity of delta 5 desaturase was studied. Fat-free diet produces a reduction in the conversion of eicosa-8,11,14-trienoic acid to arachidonic acid. The addition of the cis-omega 6 acids, linoleic, gamma-linolenic or arachidonic to the diet produces an increase of eicosatrienoic acid desaturation, shifting delta 5 desaturase activity towards the controls on a balanced diet. This reactivation is apparently produced by induction of enzyme biosynthesis since linoleate effect was suppressed by simultaneous cycloheximide injection. On the contrary, no changes in delta 5 desaturation activity were found when the diet was supplemented with palmitic or 9-trans,12-trans-linoleic acid. The changes on the activity of delta 5 desaturase were compared with the fatty acid composition of plasma and liver microsomes.

Animals↗

Effect of environmental temperature changes on rat liver fatty acid desaturases.

Female rats warm-adapted at 30-32 C for 20-25 days and then shifted to 13-15 C for 12, 24, 48, 72 and 120 hr showed that delta 9 desaturase and fatty acid synthetase activity decay after 24 hr of cold exposure, while delta 6 and delta 5 desaturases were increased after this period of time. These results were confirmed by an increase of arachidonic acid of heart and liver microsomes phosphatidylcholine and a decrease of oleic acid. Neither NADH-cyt b5 reductase nor NADH-cyt c reductase activity of liver microsomes were significantly affected. Male rats warm-adapted under the same conditions and then shifted to 13-15 C for 120 hr did not show significant changes in fatty acid synthetase, delta 9 and delta 6 desaturases and enzymes of the microsomal electron transport chain. Therefore, the desaturase response to environmental temperature changes could be plausibly linked to female hormones.

Animals↗

Turnover of low density lipoproteins in normal and atherosclerotic rabbits.

The turnover and composition of normal and hyperlipemic (h.l.) low density lipoproteins (LDL) of rabbits, were studied. They were obtained by ultracentrifugation and labeled by Bolton and Hunter method. Normal and h.l. LDL labeled with 125I were injected directly and crossed to both groups of rabbits. Normal and h.l. LDL had a different protein/lipid ratio. The analysis of fractional catabolic rate of LDL and the half-life of the phases of rapid and slow decay, show that h.l. LDL had a fractional catabolic rate that is the half of normal LDL and an increased half life of the phases of rapid and slow decay. Apparently, two factors: a) defective LDL receptor in the h.l. rabbit and b) different physico-chemical properties between normal and h.l. LDL, would be the reason for this difference. Besides, when normal and h.l. 125I LDL were injected into h.l. and normal rabbit, respectively, LDL changed according to the injected rabbit, as can be deduced from the analysis of the half life of the phase of slow decay.

Animals↗

Essential fatty acid status in zinc deficiency. Effect on lipid and fatty acid composition, desaturation activity and structure of microsomal membranes of rat liver and testes.

The effect of zinc deficiency on the lipid composition, fluorescence anisotropy of the membrane labeled with diphenyl hexatriene and delta 9, delta 6, and delta 5 fatty acid desaturation activity of liver and testes microsomal membranes was studied. Sixty days of zinc deficiency in weanling rats evoked a loss of hair and scaled and ridged tail. The activities of delta 6 and delta 5 desaturases, that are relevant enzymes involved in linoleic acid conversion into arachidonic acid, were decreased in both liver and testes. However, the delta 9 desaturase of liver was increased by the zinc deficiency. The arachidonic acid concentration of liver and testes microsomes was decreased. The microsomal phospholipid/cholesterol ratio was markedly decreased, and this change was correlative to an increase of the fluorescence anisotropy of membranes labeled with diphenyl hexatriene, that indicated an increase of the order parameter for diphenyl hexatriene and considering the criterium of Van Blitterswijk et al., an increase of the molecular packing of the bilayer. Zinc deficiency evoked an essential fatty acid deficiency status with low eicosa-5,8,11-trienoic acid, and decrease of delta 6 and, specially, delta 5 desaturase activity, that aggravates the symptoms and avoids compensatory biosynthesis of the polyunsaturated acids of oleic family.

Animals↗

[Essential fatty acids: its transformations and functions].

Essential fatty acids, in animals, pertain to two different fatty acid families: the linoleic and the linolenic. These, and the non-essential families of oleic and palmitoleic are produced by action of the enzymes proper. The lack of essential fatty acids produces typical symptoms that are accompanied by fatty acid compositions, also typical, utilized with diagnostic value. The biological effects of essential fatty acids can be specific and nonspecific. The latter manifest themselves particularly in the phospholipid composition and, therefore, in the structure and fluency of the membranes. In contrast, specific essential fatty acids act in the formation of prostaglandins, prostacyclins, tromboxans and leucotriens. Each essential fatty acid produces specific effects, depending on the prostanoids formed and the tissue in question.

Animals↗

Effect of different carbon sources on delta 5 desaturation activity of HTC cells.

The effect of different carbon sources on delta 5 desaturation activity in Minimal Deviation Hepatoma 7288 c (HTC) cells was studied. When HTC cells were incubated in the absence of carbon sources in the medium (fasted cells) the conversion of [1-14C]eicosa-8,11,14-trienoic acid to arachidonic acid increased significantly compared to those cells incubated in S-77 medium (fed cells). This activity was not modified if fasted cells were refed with glucose. However, the activity decreased significantly by the addition of lactalbumin hydrolysate to fasted cells. This effect can not be attributed to individual aminoacids since the addition of them to an aminoacid free medium produced no changes on delta 5 desaturation activity. The incubation of HTC cells with S-77 medium supplemented with glucose, pyruvate or glucose plus pyruvate, showed similar delta 5 desaturation activity to those cells incubated in S-77 medium alone.

8,11,14-Eicosatrienoic Acid↗

Isolation and characterization of the haemolymph lipoproteins of Triatoma infestans.

1. Three lipoproteins differing in hydrated densities were isolated by ultracentrifugal procedures from the haemolymph of adult and fasted Triatoma infestans. 2. They are the high density lipoprotein HDL (d = 1.115-1.152) and the two very high density lipoproteins VHDL-I (d = 1.190-1.231) and VHDL-II (d = 1.245-1.260). HDL was the predominant lipoprotein. 3. The total lipid content expressed as % of lipoprotein weight in HDL, VHDL-I an VHDL-II was 30.1, 7.8 ad 2.9% respectively. Diacylglycerols are the predominant lipids of HDL (38.7%) and VHDL-I (27.0%) but only amount of 6.2% in VHDL-II. 4. Triacylglycerols are minor components (about 6.0%) of all fractions. 5. The phospholipids (phosphatidylethanolamine and phosphatidylcholine), sterols, sterol esters and hydrocarbons were present in all lipoprotein fractions. 6. Phospholipids and hydrocarbons were the most abundant lipids of VHDL-II.

Animals↗

[Biochemistry of the developmental cycle of Triatoma infestans (Vinchuca). VI. Identification and lipid composition of hemolymph lipoproteins of adult males].

Three lipoproteins were separated from the haemolymph of adult males of Triatoma infestans fed on hen blood. The densities were similar to the high density lipoprotein (HDL) and to two very high density lipoproteins (VHDL) isolated from a pool of adult male and female insects fasted during twelve days. The relative distribution and composition of the three lipoproteins were studied. The fatty acids were mainly carried by the 1.3 and 1.2 diacylglycerols of high density lipoprotein. Triacylglycerols were minor components. Similarly to fasted insects, the main fatty acids were oleic and palmitic. Linoleic was also present. Very high density lipoproteins (VHDL-II) (d 1.25-1.26) were found in the haemolymph of male insects. The relative distribution of HDL and VHDL on fed and fasted insects was different.

Animals↗

[Biochemistry of the evolutive cycle of Triatoma infestans (vinchuca). V. Volatile fatty acids emission].

The composition of the volatile fatty acids emitted by Triatoma infestans of both sexes was studied. They were constituted by a mixture of the acids acetic, propionic, butyric, isobutyric, isovaleric, valeric and traces of isohexanoic and octanoic. Acetic acid was predominant followed by isobutyric and then by propionic acid. The other fatty acids are minor constituents. When acetic acid was discounted, the remaining composition was similar to the volatile fatty acid distribution pattern of Brindley gland. Both sexes showed a similar composition and therefore discard the possibility that they may function as sexual pheromones.

Acetates↗

Effect of clofibrate on fatty acid desaturation of rats treated with ethanol.

The effect of clofibrate and ethanol in the rat was studied on the following aspects of lipid composition and metabolism: liver delta 5, delta 6 and delta 9 fatty acid desaturases, fatty acid synthetase and fatty acid desaturase microsomal electron transport chain activity and serum cholesterol, triacylglycerols and high (HDL), low (LDL) and very low density lipoprotein (VLDL) levels. Clofibrate administered for 9 days (0.3% W/W) did not modify the relative composition of liver phospholipids and cholesterol, but did diminish triacylglycerol levels increased by ethanol. This effect could be explained by the possible beta-adrenergic blocking properties of clofibrate or by an increased activity of peroxisomal beta-oxidation. Clofibrate also promoted a decrease in serum cholesterol and triacylglycerol levels, delta 6 desaturase activity and a suppression of the electron transport chain as measured by NADH cytochrome b5 reductase and NADH cytochrome c reductase. The drug increased delta 9 desaturase activity and fatty acid synthetase, while no effect could be found in delta 5 desaturase activity. The hypocholesterolenic effect of clofibrate can not be explained through the delta 6 desaturase inhibition, or the fatty acid synthetase enhancement. Ethanol increased the HDL and VLDL and lowered LDL serum concentrations, while clofibrate reversed these results. Considering that clofibrate could have antiatherosclerotic effect in the rat, it is difficult to explain it through these changes in lipoprotein levels, since according to Miller and Miller low HDL levels are predictive of coronary heart disease.

Animals↗

Effect of fasting on delta 5 desaturation activity in rat liver microsomes and HTC cells.

The effect of fasting on delta 5 desaturation activity in Minimal Deviation Hepatoma 7288c (HTC) cells and in rat liver microsomes was studied. When HTC cells were incubated in the absence of carbon sources in the medium (fasted cells) the conversion of [1-14C] eicosa-8,11,14-trienoic acid to arachidonic acid increased significantly compared to those cells incubated in complete medium (fed cells). This effect was also shown in rat liver microsomes of rats fasted for 12, 24 and 48 hr. Fasting produced a decrease of the amount of ethanolamine fraction in HTC cells together with a significant increase in the specific activity of the same fraction. Fasting also modified the fatty acid composition of HTC cells and rat liver microsomes. There was observed a relative increase of 18:2 omega 6 acid. The importance of the difference in fatty acid and lipid composition among fasted and fed HTC cells and rat liver microsomes on delta 5 desaturation activity was discussed.

8,11,14-Eicosatrienoic Acid↗