Influence of Kynurenine, Neopterin, Noradrenaline and Pyridoxal-5-Phosphate on Cholesterol and Phospholipid Content and Phospholipid Biosynthesis in vitro

Pteridines ◽  
1993 ◽  
Vol 4 (3) ◽  
pp. 126-130 ◽  
Author(s):  
Vera Rudzite ◽  
Edite Jurika ◽  
Gilbert Reibnegger ◽  
Günter Weiss ◽  
Helmut Wachter ◽  
...  

Summary Incorporation of fatty acids into phospholipids has been investigated using samples of rat liver tissue homogenate, Krebs-Ringer-phosphate buffer (pH = 7.4) containing 0.3% albumin, fatty acid mixture and glyceroL The addition of L-kynurenine (4 nmol/g wet weight), D-eryhro-neopterin (5 and 30 pmol/g wet weight) and noradrenaline (4 nmol/g wet weight) to incubation medium induced an increase of saturated (palmitic acid) and decrease of poly-unsaturated (linoleic and arachidonic acid) fatty acids incorporation into phospholipids. The increase of saturated fatty acids incorporation into phospholipids was more pronounced after addition of neopterin and noradrenaline to the incubation medium while the decrease of linoleic and arachidonic acid synthesis was stimulated most with kynurenine. Moreover, kynurenine stimulated whereas neopterin depressed the oleic acid incorporation into phospholipids. These changes of fatty acid incorporation into phospholipids were followed by increase of cholesterol content in samples containing kynurenine, neopterin or noradrenalin. In contrast, phospholipid content decreased in samples containing kynurenine or noradrenalin, hut was not altered by supplementation of neopterin. Since the addition of kynurenine and neopterin to incubation medium for isolated fog heart resulted in an increased noradrenaline and decreased pyridoxal-5-phosphate content in the tissue, we also added pyridoxal-5-phosphate (4 nmol/g wet weight) to incubation medium for phospholipid biosynthesis. No change of the fatty acid incorporation into phospholipids as welI as the content of phospholipids and cholesterol in samples was observed.

Pteridines ◽  
1997 ◽  
Vol 8 (3) ◽  
pp. 201-205 ◽  
Author(s):  
Vera Rudzite ◽  
Edite Jurika ◽  
Janis Jirgensons ◽  
Inga Herpfer ◽  
Günter Weiss ◽  
...  

Summary Incorporation of fatty acids into phospholipids has been investigated using samples of rat liver tissue homogenate, Krebs-Ringer-phosphate buffer (pH=7.4) containing 0.3% albumin, fatty acid mixture and glycerol. The addition of L-kynurenine (4 nmoljg wet weight) to incubation medium induced an increase of palmitic, oleic and linolenic acid and decrease of linoleic and arachidonic acid incorporation into phospholipids. These changes of fatty acid incorporation into phospholipids were followed by increase of cholesterol and decrease of phospholipids content in samples. The addition of 3-hydroxykynurenine (1.8 and 4 nmoljg wet weight), 3-hydroxyanthranilic acid (2.2 and 4 nmoljg wet weight) ,1n..:l quinolinic acid (2.4 and 4 nmoljg wet weight) to incubation medium for phospholipid biosynthesis ill vitro induced a decrease of stearic, palrnitic and linoleic acid and an increase of oleic and especially arachidonic acid incorporation into phospholipids. These changes were accompanied by a decrease of cholesterol content in samples. The influence of kynurenine on fatty acid incorporation into phospholipids was similar to that of neopterin observed earlier. The other tryptophan degradation products behaved similar to the reduced pteridine derivatives. Our results allow to suggest that L-kynurenine decreases, while 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid increase membrane fluidity in the studied concentrations.


Pteridines ◽  
1995 ◽  
Vol 6 (2) ◽  
pp. 69-73
Author(s):  
Vera Rudzite ◽  
Edite Jurika ◽  
Gabriele Baier-Bitterlich ◽  
Helmut Wachter ◽  
Dietmar Fuchs

Summary Incorporation of fatty acids into phospholipids has been investigated using samples of rat live tissue homogenate, Krebs-Ringer-phosphate buffer (pH = 7A) containing 0.3% albumin, farry acid mixture and glycerol. The addition of sepiapterin, 7,8-dihydrobiopterin and 5.6.7.8-tetrahydrobiopterin (5 and 30 pmol g wet weight) to incubation medium induced a decrease of saturated (stearic acid) and an increase of polyunsaturated (arachidonic acid) fatty acids incorporation into phospholipids. Cholesterol content decreased, but phospholiplid content did not change in samples containing sepiapterin, 7,8-dihydrobiopterin and 5,6,7,8-tetrahydrobiopterin. No changes of fatty acid incorporation into phospholipids as well as of the content of cholesterol and phospholipids were observed in samples after the addition of xanthopterin (4 and 20 nmol/g wet weight) to incubation medium for phospholipid biosynthesis in vitro. The observations made by incubation with 7,8-dihydrobiopterin, 5,6,7,8-tetrahydrobiopterin and sepiapterin where in opposite to those made earlier employing neopterin and using the same incubation procedure.


Pteridines ◽  
2000 ◽  
Vol 11 (4) ◽  
pp. 107-120 ◽  
Author(s):  
Vera Rudzite ◽  
Edite Jurika ◽  
Matthias Jäger ◽  
Dietmar Fuchs

Abstract Impairment of lipid metabolism due to excess metabolite accumulation induced by pyridoxal-5-phosphate (P-5-P)-deficiency and/or stimulated immune system has been studied and interpreted. Decreased amounts of phospholipids as well as deviations in phospholipid classes and fatty acid composition of phospholipids have been demonstrated due to kynurenine accumulation in the blood of P-5-P-deficient cardiovascular patients and white rats as well as in cardiovascular patients with activated immune system identified by an increased neopterin concentration in the blood (dilated cardiomyopathy). The addition of P-5-P to the incubation medium for phospholipid biosynthesis in vitro did not change fatty acid incorporation into phospholipids, whereas it normalised fatty acid incorporation into phospholipids in liver homogenates received from P-5-P-deficient rats: The addition of kynurenine, neopterin and noradrenalin (accumulated m isolated heart tissue after addition of kynurenine and neopterin to incubation medium for isolated heart) to incubation medium for phospholipid biosynthesis in vitro induced an increase of saturated and a decrease of polyunsaturated fatty acid incorporation into phospholipids. These changes in fatty acid incorporation into phospholipids were followed by increased cholesterol concentrations in samples and an increased cholesterol/phospholipid ratio. Our results suggest that these changes in lipids are characteristic for decreased membrane fluidity, depressed cell cycle and lowered possibility of phospholipids to keep cholesterol in solution. P-5-P-deficiency is also accompanied with excess accumulation of homocysteine in the blood. The addition of L-homocysteine to the incubation medium for phospholipid biosynthesis in vitro was followed by inverse changes in fatty acid incorporation into phospholipids when compared with kynurenine, neopterin and noradrenalin. L-homocysteine induced a decrease of saturated and an increase of polyunsaturated fatty acid incorporation into phospholipids. The cholesterol concentration decreased in samples and the cholesterol/ phospholipid ratio decreased, too . These findings suggest that changes in lipids induced by L-homocysteine are characteristic for increased membrane fluidity and stimulated cell cycle. In this study, we have observed a similar effect to L-homocysteine effect when L-homocysteine, L-tryptophan and 5,6,7,8-tetrahydrobiopterin were added to the incubation medium for phospholipid biosynthesis in vitro. The comparison of our results with data from the literature allows to suggest that excess metabolite accumulation due to activated formation and inactivated catabolism of it plays a significant role in quantitative and qualitative changes of lipids, especially phospholipids, and therefore participates in the regulation of membrane fluidity, cell cycle of normal and malignant cells as well as in keeping cholesterol in the state of solution.


1959 ◽  
Vol 37 (7) ◽  
pp. 803-810 ◽  
Author(s):  
K. K. Carroll

Young male rats were fed synthetic diets containing either no fat or various individual fatty acids for 3 to 4 weeks. They were then killed and the incorporation of acetate-1-C14 into cholesterol and fatty acids was measured in liver slices and in scrapings of intestinal mucosa. Acetate incorporation into cholesterol by liver slices was much greater in animals fed erucic acid than in those fed no fat, palmitic, stearic, oleic, or linoleic acids. A marked differential was not observed in fatty acid incorporation but values tended to be higher on the fat-free and erucic acid diets. Erucic acid did not stimulate acetate incorporation into cholesterol by mucosa and in general mucosa seemed to be less sensitive to changes in diet. The results are discussed in relation to previously observed effects of erucic acid on cholesterol metabolism.


1984 ◽  
Vol 39 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Andreas Sauer ◽  
Klaus-Peter Heise

1.In isolated chloroplasts which are provided with essential exogenous substrates for glycerolipid biosynthesis (sn-G3P and UDPgal) the incorporation of fatty acids into lipids shows the same pH dependence as the fatty acid synthesis itself with a stromal pH optimum close to 8.5. 2.Furthermore high rates of glycerolipid biosynthesis appear to be accompanied by a preferred oleate incorporation as compared to palmitate. 3.Reinvestigations of the sn-G3P requirement of plastid lysophosphatidic acid formation with rapidly prepared substrate-free chloroplast extracts under approximately physiological conditions reveal a lower specificity of the primary sn-G3P acylation for oleate, as recently found for the fatty acid transfer from purified acyl-ACP fractions on to sn-G3P, catalyzed by purified acyl transferase 1. 4.A comparison of calculated stromal sn-G3P levels under physiological conditions (0.1- 0.3 mᴍ) with those, required for half saturation of the primary acylation reaction either with oleate (Km(sn-G3P) = 0.3 mᴍ) or palmitate (Km (sn-G3P) = 0.6 mᴍ) in chloroplast extracts suggests, that both fatty acids to be involved in lysophosphatidic acid formation within chloroplasts, although oleate would be preferred. 5.The latter observation facilitates the understanding of a palmitate accumulation in chloroplast lipid fractions, induced by increasing sn-G3P concentrations in chloroplast sus­pensions. 6.Although stimulating fatty acid synthesis from acetate in intact chloroplasts, acyl-CoA- synthesizing-conditions (presence of CoA and ATP) in the applied chloroplast extracts appear to inhibit fatty acid incorporation into sn-G3P and thus to exert a regulatory function between the plastidary and extraplastidary glycerolipid biosynthesis.


Pteridines ◽  
1998 ◽  
Vol 9 (4) ◽  
pp. 201-206
Author(s):  
Vera Rudzite ◽  
Edite Jurika ◽  
Janis Jirgensons ◽  
Bernhard Widner ◽  
Guenter Weiss ◽  
...  

Summary Incorporation of fatty acids into phospholipids has been investigated using samples of rat liver homogenate, Krebs-Ringer phosphate buffer (pH=7.4) containing 0.3% albumin, fatty acid mixture and glycerol. The addition of neopterin, serotonin (0.2 and 2.0 nmoljg wet weight) without iproniasid and 5- hydroxyindoleacetic acid (20.0 nmoljg wet weight) induced an increase of saturated and a decrease of unsaturated, especially arachidonic acid, incorporation into phospholipids. These changes were accompanied with elevated cholesterol content in samples. The addition of 5,6,7,8-tetrahydrobiopterin (5 and 30 pmolj g wet weight) and serotonin (0.2 and 2.0 nmoljg wet weight) together with iproniasid (10 nmoljg wet weight) to incubation medium for phospholipid biosynthesis in vitro induced a decrease of saturated and an increase of unsaturated, especially arachidonic acid, incorporation into phospholipids. These changes were accompanied with decreased cholesterol content in samples. The influence of serotonin without iproniasid and 5-hydroxyindoleacetic acid was similar to that of neopterin, kynurenine and noradrenaline observed earlier, while the influence of serotonin together with iproniasid was similar to that of 5,6,7,8- tetrahydrobiopterin and its precursors found earlier. Our results allow to suggest that in the studied concentrations serotonin increases, while 5-hydroxyindoleacetic acid decreases membrane fluidity.


1983 ◽  
Vol 61 (12) ◽  
pp. 1265-1271 ◽  
Author(s):  
R. Roy Baker ◽  
Huu-yi Chang

The incorporation of radioactive palmitate, oleate, linoleate, and arachidonate into endogenous triacylglycerols was followed in vitro using neuronal nuclei (N1) isolated from cerebral cortices of 15-day-old rabbits. Specific rates of incorporation of fatty acids into N1 triacylglycerols were 33–42 times and more than 100 times the corresponding values for cerebral cortex homogenates and microsomal fractions (P3), respectively. Acyl-CoA synthetase specific activities in N1 were 2.2 to 3.2 times the specific rates for fatty acid incorporation into N1 triacylglycerols. Using single fatty acids, N1 acyl-CoA synthetase showed a preference for linoleate which was more highly marked in linoleate–palmitate and linoleate–arachidonate competitions. In fatty acid incorporation into N1 triacylglycerols a preference for linoleate in competition with palmitate was noted; however, there was also a relatively higher utilization of arachidonate shown competitively than was noted in acyl-CoA synthesis. The data suggested that N1 diacylglycerol acyl transferase shows a selectivity for arachidonoyl-CoA in comparison with CoA esters of palmitate or oleate. Molecular class analyses of radioactive triacylglycerol products indicated that native endogenous N1 diacylglycerols bearing arachidonate or fatty acids of equal or higher unsaturation were used preferentially in N1 triacylglycerol synthesis. This preference was significantly decreased when higher levels of endogenous diacylglycerols were produced in N1 following a phospholipase C preincubation.


Blood ◽  
1994 ◽  
Vol 84 (4) ◽  
pp. 1283-1287
Author(s):  
DW Allen ◽  
N Manning

Spur cell anemia is a hemolytic anemia seen in severe alcoholic cirrhosis that is characterized by unusual morphology and a decreased ratio of phospholipids to cholesterol in the erythrocyte membrane. We hypothesized that defective phospholipid repair may contribute to the red blood cell (RBC) phospholipid abnormalities of spur cell anemia. Therefore, we compared RBCs from normal control subjects with RBCs from spur cell anemia patients. The incorporation of [14C] arachidonic acid into the phospholipids and acylcarnitine (acyl-Cn) of spur cells and normal RBCs was analyzed by a direct-phase high performance liquid chromatography column to separate both the phospholipids and acyl-Cn. There was less uptake of the [14C] arachidonate into phosphatidylethanolamine of spur cell RBCs (12.9% +/- 1.0%) compared with normal RBCs (20.5% +/- 2.8%; P = .0245). However, more arachidonate was incorporated into the acyl-Cn of spur cells (spur cell acyl-Cn [24.5% +/- 2.9%] v normal control acyl-Cn [10.1% +/- 1.9%]; P = .0018). We conclude that phospholipid biosynthesis is inhibited and that acyl-Cn formation is spared in spur cell anemia RBCs. These metabolic changes may help account for the lipid abnormalities seen in spur cell anemia RBCs and contribute to the hemolytic process.


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