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[Protein digestibility and absorption of amino acids in various segments of the digestive tract of pigs. 2. Protein and amino acid balances at the end of the small intestine and of the whole digestive tract (apparent and true protein and amino acid digestibility)].

Growing pigs with ileum and ileocecal re-entrant canulae were given 5 different rations (pig fattening feed 1 and 2, rations with dried skim milk, wheat gluten + lysine and wheat + wheat gluten + lysine). The crude protein and amino acid excretion was quantitatively determined with ileum chyme and feces. The calculation of the amino acid balances (apparent and true digestibility) at the end of the small intestine, at the end of the wholedigestive tract and the isolated colon showed characteristic differences for the individual amino acids. On ileum level the amino acids with relatively high endogenous quotas, threonine, tryptophane, alanine, aspartic acid and glycine showed a distinctly lower, the amino acids arginine, methionine, phenylalanine, glutamic acid, proline and tyrosine a distinctly higher digestibilityhan crude protein. In comparison of the values on the feces level, including the true digestibility, these differences are largely balanced out. At the end of the small intestine the absorption of the amino acids is in the main completed. The disappearance rate of amino acids from the colon shows large differences with reference to the different rations as well as the individual amino acids. They were particularly high for various rations as far as proline, tryptophane, glycine and cystine are concerned. If wheat gluten + lysine rations were given, a net synthesis of methionine in the colon could be proved.

Amino Acids↗

[Effect of glutamic acid content of the diet on isotope-labeled glutamic acid catabolism in rats. 1. The course of 14CO excretion following intragastric administration of 14C-glutamic acid].

Male rats received in 8 groups of 10 animals each for a period of 7 days 7 synthetic diets and one semisynthetic diet on maintenance requirement level. A L-amino acid mixture corresponding to the pattern of egg protein without glutamic acid was the protein source of the synthetic diets. Glutamic acid was supplemented successively from 0 to 58 mol-% of the total amino acid content. The crude protein source of diet 8 was whole egg powder. On the 8th day of experiment 5 animals per group were labelled by intragastric infusion (i.g.) with 14C-U-glutamic acid. During the following 24 hours the excretion of CO2 and 14CO2 was measured. Throughout the experimental feeding body weight was relative constant, however, when the synthetic diets were fed it was necessary to increase the daily amount of energy from 460 to 480 kJ/kg0,67. The relative 14CO2-excretion within 24 hours was 68-75% of the dose. However, the main part of the amount of radioactivity excreted during 24 hours was found after 4 to 6 hours already. Exponential functions calculated from the data of cumulative 14CO2-excretion suggest the existence of a fast process of 14CO2-formation directly from 14C-glutamic acid, reaching a plateau within 2 hours and a slow process of oxidation of intermediates of glutamic acid metabolism, causing a continued 14CO2-formation even after 24 hours. The oxidation of 14C-glutamic acid to CO2 decreased 2 to 14 hours after i.g. labelling if the glutamic acid content of the diet increased. The same was found for the specific radioactivity of 14CO2. A storage of intermediates of glutamic acid before degradation was assumed.

Animals↗

Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipids and fatty acid profiles in women.

BACKGROUND: Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and gamma-linolenic acid (GLA) have lipid-modifying and antiinflammatory properties. The effects of supplement mixtures of these fatty acids on plasma lipids and the fatty acid compositions of serum phospholipids have received little attention. OBJECTIVE: The objective was to determine the effects of different levels of GLA supplementation together with a constant intake of EPA plus DHA on the triacylglycerol-lowering effect of EPA plus DHA alone and on the fatty acid patterns (eicosanoid precursors) of serum phospholipids. DESIGN: Thirty-one women were assigned to 1 of 4 groups, equalized on the basis of their fasting triacylglycerol concentrations. They received supplements providing 4 g EPA+DHA (4:0, EPA+DHA:GLA; control group), 4 g EPA+DHA plus 1 g GLA (4:1), 2 g GLA (4:2), or 4 g GLA (4:4) daily for 28 d. Plasma lipids and fatty acids of serum phospholipids were measured on days 0 and 28. RESULTS: Plasma triacylglycerol concentrations were significantly lower on day 28 than on day 0 in the 4:0, 4:1, and 4:2 groups. LDL cholesterol decreased significantly (by 11.3%) in the 4:2 group. Dihomo-gamma-linolenic acid increased significantly in serum phospholipids only in the 4:2 and 4:4 groups; however, total n-3 fatty acids increased in all 4 groups. CONCLUSIONS: A mixture of 4 g EPA+DHA and 2 g GLA favorably altered blood lipid and fatty acid profiles in healthy women. On the basis of calculated PROCAM values, the 4:2 group was estimated to have a 43% reduction in the 10-y risk of myocardial infarction.

Adult↗

Fatty acid metabolism assessed by 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded hearts.

BACKGROUND: The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPARalpha and fatty acid oxidation enzymes in volume-overloaded rabbit hearts. METHODS: Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. (125)I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by beta-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPARalpha and fatty acid oxidation enzymes were examined by Western blotting. RESULTS: Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0.06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by beta-oxidation was faster than the sham-control hearts (P < 0.05). However, protein levels of PPARalpha and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits. CONCLUSIONS: These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPARalpha and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli.

Animals↗

Profile of urinary bile acids in infants and children: developmental pattern of excretion of unsaturated ketonic bile acids and 7beta-hydroxylated bile acids.

Unusual bile acids, such as unsaturated ketonic and 7beta-hydroxylated bile acids, have been detected in urine early in life. To elucidate the normal profiles of usual and unusual urinary bile acids in the neonatal and pediatric periods, we measured the concentrations of 28 kinds in urine from normal newborns, infants, and children by gas chromatography-mass spectrometry. The mean total bile acid/Cr ratio in 7-d-old infants was significantly higher than in subjects of other age groups (birth, 2-4 mo, 5-7 mo, 11-12 mo, 2-3 y, 9-14 y, and adult) (p < 0.05). Relatively large amounts of unusual bile acids were detected during infancy, especially during the period up to 1 mo of age. At that time, 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5bet a-cholan-24-oic, 7alpha, 12alpha-dihydroxy-3-oxo-5beta-chol-1-en-24-oic, and 7alpha,12alpha-dihydroxy-3-oxo-4-cholen-24-oic acids were predominant among the unusual urinary bile acids present. Moreover, the levels of 3alpha,7beta,12alpha-trihydroxy-5beta-cholan+ ++-24-oic acid increased significantly after 2-4 mo of age. These results indicate that bile acid synthesis and metabolism in the liver of developing infants are significantly different from that occurring in the liver of adults. Significant amounts of urinary isomerized 7beta-hydroxylated bile acids were detected after late infancy, probably because of changes in the intestinal bacterial flora response to a change in nutrition. We describe, for the first time, evidence of the epimerization of the 7alpha-hydroxyl group of cholic acid, which may be unique to human development.

Adolescent↗

Effect of ascorbic acid on iron absorption from different types of meals. Studies with ascorbic-acid-rich foods and synthetic ascorbic acid given in different amounts with different meals.

The effect of ascorbic acid on the absorption of non-heme iron was studied in 299 subjects. Different meals in which the non-heme iron was labelled with two different radio-iron isotopes were served with and without ascorbic acid to the same subject. Other meals containing foods with a known high content of ascorbic acid were also studied. Studies were also made giving different amounts of ascorbic acid with different meals. Marked differences in the enhancement of iron absorption were seen when ascorbic acid was given in different meals. It is suggested that ascorbic acid promotes iron absorption from the diet by reducing the negative effect on iron absorption of certain ligands such as phytates and tannins present in the diet. This interpretation is supported by observations that the most pronounced effects of ascorbic acid were found in meals with a high content of ligands known to inhibit iron absorption. Crystalline ascorbic acid and native ascorbic acid in foods appeared to have the same effect in promoting absorption of iron. The results indicate that ascorbic acid has a key physiologic role in facilitating the absorption of non-heme iron from the diet and that about 50 mg of the vitamin in each main meal is desirable for optimum effect.

Adult↗

An improved method for the measurement of total lipid-bound sialic acids after cleavage of alpha 2,8 sialic acid linkage with Vibrio cholerae sialidase in the presence of cholic acid, SDS and Ca2+.

In the measurement of total lipid-bound sialic acids involving periodic acid oxidation, as in the periodate-resorcinol assay, the inner sialic acids of disialoglycolipids (such as GD3 and GD2) are not involved because their alpha 2,8 ketosidic linkages are resistant to periodic acid oxidation, even after acid/enzyme hydrolysis or alkali pretreatment. However, the sialic acids from these glycolipids can be recovered completely after cleavage of alpha 2,8 linkages by V. cholerae sialidase in the presence of cholic acid, sodium dodecyl sulphate and calcium. Interestingly, removal of calcium or detergent(s) or both significantly minimizes the sialidase action on the disialyl residues of these gangliosides. Therefore, we recommend sialidase (Vibrio cholerae) pretreatment of the glycolipids in the presence of cholic acid, SDS and Ca2+ for complete recovery of sialic acids from di- and polysialogangliosides and for accurate measurement of total lipid-bound sialic acids by periodate-resorcinol assay.

Calcium↗

Blood fatty acid composition of pregnant and nonpregnant Korean women: red cells may act as a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus.

Relative fatty acid composition of plasma and red blood cell (RBC) choline phosphoglycerides (CPG), and RBC ethanolamine phosphoglycerides (EPG) of pregnant (n = 40) and nonpregnant, nonlactating (n = 40), healthy Korean women was compared. The two groups were of the same ethnic origin and comparable in age and parity. Levels of arachidonic (AA) and docosahexaenoic (DHA) acids were lower (P < 0.05) and palmitic and oleic acids higher (P < 0.0001) in plasma CPG of the pregnant women. Similarly, the RBC CPG and EPG of the pregnant women had lower AA and DHA (P < 0.05) and higher palmitic and oleic acids (P < 0.01). The reduction in DHA and total n-3 fatty acids in plasma CPG of the pregnant women was paralleled by an increase in docosatetraenoic (DTA) and docosapentaenoic (DPA) acids of the n-6 series and in DPA/DTA ratio. In the RBC phospholipids (CPG and EPG) of the pregnant women, DTA and DPA acids of the n-6 series and DPA/DTA ratio did not increase with the decrease of the n-3 metabolites (eicosapentaenoic acid, DPA, and DHA) and total n-3. Since pregnancy was the main identifiable variable between the two groups, the lower levels of AA and DHA in RBC CPG and EPG of the pregnant women suggest that the mothers were mobilizing membrane AA and DHA to meet the high fetal requirement for these nutrients. It may also suggest that RBC play a role as a potential store of AA and DHA and as a vehicle for the transport of these fatty acids from maternal circulation to the placenta to be utilized by the developing fetus.

Adult↗

Convulsant action of intracerebroventricularly administered l-kynurenine sulphate, quinolinic acid and other derivatives of succinic acid, and effects of amino acids: structure-activity relationships.

Succinic acid, and the derivatives which have been tested, i.e. phthalic, l-glutamic, l-aspartic, citric and laevulinic acids, in doses of 5,2,5,20,20 and 50 micrograms, respectively, as well as l-kynurenine sulphate and quinolinic acid, injected into the brain ventricles in mice, induced clonic seizures. When administered intraperitoneally or orally they antagonize strychnine-induced seizures. The convulsant effect of l-kynurenine sulphate was observed only when the pH of the solution was 4.0 or lower, while the actions of the other drugs tested were not dependent upon pH. Control intraventricular injections of 5 microliters of 0.06 N sulphuric acid (equivalent to 16.7 micrograms of SO4(2-), the same dose as was injected when a convulsant dose of 50 micrograms of l-kynurenine was administered) induced seizures in 25% of the mice. It is suggested that the convulsant effect of quinolinic acid and l-kynurenine sulphate is related to a moiety of succinic acid (O = C-C-C-C = O). The effect of l-kynurenine sulphate comprises the action of the cation of kynurenine and that of the anion of sulphuric acid. Reduction of the convulsant effect of l-kynurenine sulphate by alpha-amino acids and taurine is presumably related to a "shielding" of both amino- and carbonyl groups of 1-kynurenine. There is no evidence that l-kynurenine sulphate, in small doses, shares the central effects of the inhibitory amino acids.

Amino Acids↗

In vivo and in vitro effects of gamma-linolenic acid and eicosapentaenoic acid on prostaglandin production and arachidonic acid uptake by human endometrium.

This study examines the effect of a 6 month dietary supplement of either gamma-linolenic acid (GLA) or eicosapentaenoic acid (EPA) on the synthesis of prostaglandins E2 and F2 alpha by the endometrium of women with regular menstrual cycles. Samples of endometrium, obtained pre- and post-treatment, were incubated in vitro for 2 h and the prostaglandins E2 and F2 alpha released into the medium measured by radioimmunoassay. The ability of the tissue to take up 14C-arachidonic acid before and after treatment was also examined. Both GLA and EPA caused a marked decrease in the synthesis of prostaglandins E2 and F2 alpha (P < 0.001) but under the experimental conditions used, there was no consistent effect on arachidonic acid uptake. Body mass index, serum testosterone, fasting insulin and serum sex hormone-binding globulin (SHBG) concentrations did not change during the 6 month treatment period. An effect of GLA and EPA on arachidonic acid uptake into endometrial tissue explants was demonstrated in vitro. In the presence of both GLA and EPA, uptake into phospholipids (particularly phosphatidylcholine) decreased while uptake into triglycerides increased. Free 14C-arachidonic acid levels (that which could not be removed from the tissue by washing) also increased. Suppression of endometrial prostaglandin E2 and F2 alpha synthesis following GLA or EPA supplementation can be explained as direct competition between these fatty acids and arachidonic acid (the precursor of 2-series prostaglandins) for incorporation into membrane phospholipids. The amount of arachidonic acid available for 2-series prostaglandin synthesis will therefore be reduced. However, other mechanisms may exist which need to be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice.

In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-kappaB, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-kappaB, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P<0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P<0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P<0.05). Folic acid also reduced VPA-induced alterations in p53, NF-kappaB, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-kappaB, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

Animals↗

delta 22-Ursodeoxycholic acid, a unique metabolite of administered ursodeoxycholic acid in rats, indicating partial beta-oxidation as a major pathway for bile acid metabolism.

We describe for the first time the identification of 3 alpha, 7 beta-dihydroxy-5 beta-chol-22-en-24-oic acid (delta 22-UDCA) in the plasma, bile, intestinal contents, and liver tissue of Sprague-Dawley rats after intravenous and oral administration of ursodeoxycholic acid (UDCA). Infusion of [2,2,4,4-2H4]UDCA confirmed delta 22-UDCA to be a specific metabolite of UDCA. Definitive confirmation of this unique and major metabolite was established by liquid secondary ionization mass spectrometry and gas chromatography-mass spectrometry by comparison of the retention index and mass spectrum with an authentic standard of delta 22-UDCA. When rats were fed a diet containing 1.0% UDCA, high concentrations of delta 22-UDCA were found in the plasma (40.3 +/- 11.8 mumol/L) and liver tissue (300.9 +/- 64.2 nmol/g of tissue), and these represented 36% and 57%, respectively, of the UDCA concentration. In animals fed 0.4% and 1.0% UDCA, the mass of delta 22-UDCA in the jejunum was high (7.5 +/- 0.9 and 6.6 +/- 0.6 mg, respectively), accounting for 50-60% of the total UDCA, but diminished markedly along the intestine, accounting for < 3% of the total UDCA in the colon. Although delta 22-UDCA was not found in biological samples from control rats, delta 22-beta-muricholic and delta 22-omega-muricholic acids were normal constituents of plasma and intestinal contents and were major muricholate isomers in liver tissue and bile. Synthesis of delta 22-bile acids appears to be highly specific toward bile acids possessing a functional 7 beta-hydroxyl group. We presume that, in common with pathways for endogenous bile acid synthesis, partial side-chain oxidation of UDCA occurs in the peroxisome with formation of alpha/beta unsaturation; since UDCA has only a 5-carbon side chain, release of propionic or acetic acid is not possible, beta-oxidation proceeds no further, and delta 22-UDCA is formed. While the mechanism of formation and physiological significance of delta 22-bile acids remain to be established, our data indicate that partial beta-oxidation is a quantitatively important pathway for endogenous bile acid synthesis and for UDCA metabolism in this species.

Animals↗

Influence of chronic ascorbic acid deficiency and excessive ascorbic acid intake on bile acid metabolism and bile composition in the guinea pig.

The influence of chronic ascorbic acid (AA) deficiency and excessive ascorbate consumption on bile acid metabolism, liver and plasma cholesterol levels, hepatic microsomal cytochromes and biliary lipid composition was investigated. Male weanling guinea pigs were fed a cereal-based scorbutigenic diet supplemented with four levels of AA for 7 weeks: deficient, 15 and 30 mg/kg; control, 500 mg/kg; and excess, 20,000 mg/kg. Bile acid kinetic parameters were determined following the intraperitoneal administration of [24-14C] chenodeoxycholic acid. Dietary extremes of AA caused similar alterations in the parameters studied. Relative to the control group, the deficient and excess groups exhibited reduced cytochrome P-450 concentration, lower cholesterol 7 alpha-hydroxylase activity, lower bile acid turnover rate, prolonged bile acid half-life and increased plasma and liver cholesterol concentrations. Deficient and excess groups also exhibited lower biliary cholesterol saturation (i.e., increased bile acid-neutral sterol ratios) than controls. Urinary bile acid excretion was 2- to 3-fold higher in excess guinea pigs than in the other three groups. The data demonstrate the exceptional susceptibility of cholesterol 7 alpha-hydroxylase activity to alteration by dietary extremes of AA, resulting in marked inhibition of bile acid synthesis and elevation of cholesterol levels by both inadequate and excessive AA intake.

Animals↗

Carp oil or oleic acid, but not linoleic acid or linolenic acid, inhibits tumor growth and metastasis in Lewis lung carcinoma-bearing mice.

I examined the effects of carp oil, oleic acid, linoleic acid and linolenic acid on tumor growth and metastasis to the liver in mice implanted intrasplenically with highly metastatic Lewis lung carcinoma (LLC) tumors. Carp oil (0.1 or 0.2 mL per mouse) significantly reduced tumor growth and metastasis to the liver. Carp oil at 100 or 1000 mg/L inhibited the DNA synthesis in LLC cells, the capillary-like tube formation of human dermal microvascular endothelial cells (HMVEC) at 1000 mg/L and the adherence of LLC cells to HMVEC at 10 to 1000 mg/L (in vitro). Carp oil (0.2 mL per mouse) inhibited the angiogenesis induced by Matrigel supplemented with vascular endothelial growth factor (VEGF) and heparin (in vivo). Antitumor and antimetastatic actions of carp oil might be partly attributable to the inhibition of DNA synthesis in LLC cells and angiogenesis through the inhibition of the adherence of LLC cells to the microvascular endothelium. Oleic acid (0.1 or 0.2 mL per mouse) significantly inhibited the metastasis to the liver, but it had no effect on the primary solid-tumor growth. Oleic acid inhibited the angiogenesis in both in vitro and in vivo models. Oleic acid at 1000 micromol/L inhibited the DNA synthesis in LLC cells but did not affect the DNA synthesis in HMVEC. These inhibitory actions of oleic acid may be attributable to the inhibition of angiogenesis induced by the tumor. Linoleic acid and linolenic acid had no effect on tumor growth or metastasis to the liver.

Animals↗

Cysteine sulfinic acid in the central nervous system: specific binding of [35S]cysteic acid to cortical synaptic membranes--an investigation of possible binding sites for cysteine sulfinic acid.

Specific binding sites for cysteine sulfinic acid, an excitatory amino acid, in crude synaptic membrane fractions of rat cerebral cortex were examined, using L-[35S]cysteic acid as a ligand. Two specific binding systems of [35S]cysteic acid were found, one Na+-dependent and the other Na+-independent. The Na+-independent specific binding of [35S]cysteic acid was saturable, with a Kd of 474 nM and Bmax of 3.29 pmol/mg protein. The binding was optimal at pH 7.4 and at 37 degrees C. Treatment of the membranes with proteases, concanavalin A, or Triton X-100 markedly reduced the binding. Of various compounds related to cysteic acid, L-cysteine sulfinic acid was the most effective competitor of this binding. These results indicate the existence of an Na+-independent specific binding site for cysteic acid in the synaptic membrane of rat cerebral cortex, which may be different from that for glutamate. Possible involvement of cysteine sulfinic acid as an endogenous ligand for this binding site is discussed.

Amino Acids, Sulfur↗

Biochemical changes in progressive muscular dystrophy, XVI. Effect of glutamic acid, aspartic acid and glycine on the amino acid content of skeletal muscle of dystrophic mice.

The effect of exogenous administration of glutamic acid (GL), aspartic acid (A) and glycine (G) on individual amino acids in the free amino acid pool was studied in skeletal muscles of 60- to 70-day-old normal (N) and dystrophic (D) mice. Both N and D mice received either 0.25 ml of saline (S) or 250 mg/kg weight of GL, A or G in 0.25 ml S subcutaneously for 13 days. GL, A, G or S did not cause any significant changes in the body and skeletal muscle weights of either group. Most of the individual amino acids were increased in skeletal muscles of GL-treated mice and were decreased in A- or G-treated animals compared to S administration in the N group. The picture was more dramatic in the D group: GL-induced amino acid elevations were more pronounced than the values of N- or S-treated D controls. A and G elicited amino acid increases in D mice compared to their S-treated counterparts. Most of the individual amino acids in skeletal of the D group were decreased relative to N mice after S, GL or A administration. This was evident when the D/N ratio was calculated for S, GL and A. The situation was very different after G administration since of the individual amino acids were augmented in the skeletal muscle of D mice compared to N animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

[Effect of combination therapy of clofibric acid and nicotinic acid derivatives on fatty acid metabolism in hyperlipoproteinemia].

71 patients (42 males and 29 females at the age of 45-76 years) with primary hyperlipoproteinaemia were treated with clofibrin acid and derivatives of nicotinic acid during 3 years. Gas-chromatographic analyses of the composition of fatty acids of their serum cholesterol ester and triglyceride fractions showed an increase of linoleic, linolenic, arachidonic, eicosapentaenic acid as well as a decrease of palmitinic, palmitoleinic, stearic, oleic and eicosatrienic acid under treatment. The changes were more efficient than under monotherapy. Selective competitive inhibition of unesterified fatty acid, blocking of lipolysis, influence on the hepatogenic metabolism of fatty acids and on the LCAT as well as better utilization of the alimentary repeatedly unsaturated fatty acids were discussed as possible mechanism. The increase of the polyunsaturated fatty acids with their interrelations to the prostaglandin metabolism must be seen in the sense of a vasoprotective effect.

Aged↗

Effect of dietary fats on arachidonic acid and eicosapentaenoic acid biosynthesis and conversion to C22 fatty acids in isolated rat liver cells.

The desaturation, chain elongation and esterification of [1-14C]eicosapentaenoic acid, [1-14C]arachidonic acid, [1-14C]eicosatrienoic acid, [1-14C]linolenic acid and [1-14C]linoleic acid were studied in isolated liver cells. Rats fed diets with either 15% hydrogenated coconut oil or 15% partially hydrogenated marine oil, both deficient in essential fatty acids, 15% soybean oil or standard pellet diet with 6% fat, were used. The delta 4-desaturation of 22:5(n - 3) and 22:4(n - 6) as well as the delta 6-desaturase activity was distinctly higher in cells from animals fed coconut or marine oil than with soybean oil or standard pellet. The rate of delta 5-desaturation of 20:3(n - 6) and 20:4(n - 3) was nearly the same in cells from rats fed coconut, marine and soybean oils and higher than with standard pellet. The chain elongation of 20:5(n - 3) to 22:5(n - 3) was distinctly more pronounced than the elongation of 20:4(n - 6) with all four diets. 20:5(n - 3) was mainly esterified in the phospholipids with marine and coconut oils, and mainly in triacylglycerol with standard pellet and soybean oils. The proportion of [1-14C]20:4(n - 6) in the phospholipids to that in triacylglycerol decreased in the order marine oil greater than coconut oil greater than standard pellet greater than soybean oil. The different endogenous arachidonic acid content in the phospholipids induced by the different diets increased in the same order. 20:5(n - 3) was rapidly esterified in triacylglycerol and phospholipids, then liberated especially from the triacylglycerol fraction, chain elongated to 22:5(n - 3) and reesterified.

Animals↗