SEARCH · PubMed Health

Results for “ACID”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources

PubMed1983

Kinetic analysis of the accumulation of gamma-aminobutyric acid by particulate fractions of rat brain: comparison of the effects of nipecotic acid and cis-3-aminocyclohexane-1-carboxylic acid.

Kinetic analyses indicate that nipecotic acid and cis-3-aminocyclohexane-1-carboxylic acid (cis-3-ACHC) inhibit GABA accumulation by similar mechanisms of action. Both amino acids are competitive inhibitors of particulate GABA accumulation when GABA and the inhibitor are added simultaneously to tissue fractions. However, preincubating the tissue with either amino acid produces noncompetitive inhibition of GABA accumulation at low concentrations of inhibitor and mixed inhibition at higher concentrations. The possible roles of intrasynaptosomal mechanisms and of astroglia in producing these effects are discussed. The most notable difference between cis-3-ACHC and the other amino acid inhibitors of GABA accumulation, such as nipecotic acid, cis-4-OH-nipecotic acid, guvacine, beta-proline, homo-beta-proline, and 2,4-diaminobutyric acid (DABA), is that cis-3-ACHC is approximately 3.5 times more potent as an inhibitor following preincubation. Thus, while cis-3-ACHC does inhibit GABA transport, its major site of action in the synaptosome may be intracellular.

Amino Acids↗

PubMed1984

Uptake of arachidonic acid, arachidic acid, oleic acid and their incorporation into phospholipids and triacylglycerols of isolated murine hepatocytes. Effect of thrombin-antithrombin III complex.

Uptake and metabolism of arachidonic acid, arachidic acid and oleic acid were investigated in isolated hepatocytes prepared from mouse liver with the collagenase perfusion method. The rate of uptake of arachidonic acid was time- and concentration- dependent. 94-98% of the arachidonic acid was incorporated into the phospholipid and triacylglycerol fractions following a 60 min incubation period at 37 degrees C. In the presence of thrombin-anti-thrombin III complex a change in the distribution of arachidonic acid incorporated into lipid fractions was found, i.e. increased incorporation into phosphatidyl-serine and phosphatidylethanolamine, whereas the uptake was not altered. There was no change in the uptake and incorporation of arachidic acid and oleic acid.

Animals↗

PubMed1996

Syntheses of (-)-Isocitric Acid Lactone and (-)-Homoisocitric Acid. A New Method of Conversion of Alkynylsilanes into the Alkynyl Thioether and Corresponding Carboxylic Acids.

A simple, stereoselective synthesis of natural isocitric and homoisocitric acids from a common alkynylsilane correlates the stereochemistry of these acids. Starting with dimethyl D-malate dianion, methyl 2-hydroxy-3-carbomethoxy-6-(trimethylsilyl)-5-hexynoate (6a) was prepared with a good stereoselectivity (threo/erythro 90/10). Oxidative cleavage of the triple bond provided isocitric acid lactone (8') in 15% overall yield starting from D-malic acid diester 1. The synthesis of homoisocitric acid relied on a new method of conversion of alkynylsilane to alkynyl thioether, which is converted to the carboxylic acid of the same chain length. Addition of benzenesulfenyl chloride to (trimethylsilyl)alkyne 6b and elimination of trimethylsilyl chloride gave the corresponding thioether 10, which by acid hydrolysis gave homoisocitric acid (11) in a 24% yield from D-malic acid ester. This novel method of conversion of alkynylsilane to the corresponding acid was illustrated with several other alkynyltrimethylsilanes.

Journal Article↗

PubMed2005

Biological activities of conjugated fatty acids: conjugated eicosadienoic (conj. 20:2delta(c11,t13/t12,c14)), eicosatrienoic (conj. 20:3delta(c8,t12,c14)), and heneicosadienoic (conj. 21:2delta(c12,t14/c13,t15)) acids and other metabolites of conjugated linoleic acid.

The elongated form of conjugated linoleic acid (CLA), conjugated eicosadienoic acid (CEA, conj. 20:2delta(c11,t13/t12,c14)), was generated from CLA by liver microsomal fractions. Subsequent testing showed that dietary CEA significantly reduced body fat, and increased lean mass similar to CLA when compared to controls. CEA also decreased lipoprotein lipase activity and triacylglyceride, and increased glycerol release in 3T3-L1 adipocytes, correlated with the trans-12,cis-14 isomer, but CEA required a longer incubation period than cells treated with CLA. Based on the fact that CEA fed animals had CLA in tissue, we suggest that the effect of CEA is due to the CLA converted from CEA in the system. The delta-6 desaturated and elongated form of trans-10,cis-12 CLA (conjugated eicosatrienoic acid, CETA, conj. 20:3delta(c8,t12,c14)) inhibited LPL activity and increased glycerol release but was less active than trans-10,cis-12 CLA or CEA. The 21-carbon conjugated fatty acid, conjugated heneicosadienoic acid (CHDA, conj. 21:2delta(c12,t14/c13,t15)), was not active on LPL inhibition, triacylglyceride, or glycerol release in 3T3-L1 adipocytes. We also provide evidence that CLA was metabolized to conjugated dodecadienoic acid (conj. 12:2delta(c3,t5/t4,c6)). In addition, there were indications of the presence of conjugated tetradecadienoic acid (conj. 14:2delta(c5,t7/t6,c8)), suggesting that CLA can be metabolized through fatty acid beta-oxidation. This is the first work to report the presence of conjugated 12 and 14 carbon fatty acids, originated from CLA, and the biological activities of CEA, CETA and CHDA.

Animals↗

PubMed1999

Methylated eicosapentaenoic acid and tetradecylthioacetic acid: effects on fatty acid metabolism.

We introduced methyl or ethyl groups to the 2- or 3-position of the eicosapentaenoic acid (EPA) molecule to investigate whether the branching of EPA could influence its hypolipidemic effect in rats. The most effective branching involved two methyl groups in the 2-position and one methyl group in the 3-position. These EPA derivatives increased hepatic mitochondrial and peroxisomal beta-oxidation and decreased plasma lipids concomitant with suppressed acetyl-coenzyme A (CoA) carboxylase (EC 6.4.1.2) and fatty acid synthase (EC 2.3.1.85) activities. This was followed by elevated activities of camitine O-palmitoyltransferase (EC 2.3.1.21) and possibly 2,4-dienoyl-CoA reductase (EC 1.3.1.34), as well as induced mRNA levels of these enzymes and fatty acyl-CoA oxidase. The fatty acid composition in liver changed, with an increased 18:1 n-9 content, whereas the expression of delta9-desaturase remained unchanged. We investigated the flux of fatty acids in cultured hepatocytes, and found that oxidation of [1-14C]-labeled palmitic acid increased but the secretion of palmitic acid-labeled triglycerides decreased after addition of 2-methyl-EPA. The fatty acyl-CoA oxidase (EC 1.3.3.6) activity in these cells remained unchanged. A significant negative correlation was obtained between palmitic acid oxidation and palmitic acid-labeled synthesized triglycerides. To investigate whether the hypolipidemic effect occurred independently of induced peroxisomal beta-oxidation, we fed rats 2-methyl-tetradecylthioacetic acid. This compound increased the peroxisomal but not the mitochondrial beta-oxidation, and the plasma lipid levels were unchanged. In conclusion, EPA methylated in the 2- or 3-position renders it more potent as a hypolipidemic agent. Furthermore, this study supports the hypothesis that the mitochondrion is the primary site for the hypolipidemic effect.

Animals↗

PubMed2004

Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+).

PURPOSE: The purpose of this study was to analyze the transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the Na(+)/Cl(-)-coupled amino acid transporter ATB(0,+). METHODS: The interaction of amino acid esters and valganciclovir with the cloned rat ATB(0,+) was evaluated in a mammalian cell expression system and in the Xenopus oocyte expression system. RESULTS: In mammalian cells, expression of ATB(0,+) induced glycine uptake. This uptake was inhibited by valine and its methyl, butyl, and benzyl esters. The benzyl esters of other neutral amino acids were also effective inhibitors. Valganciclovir, the valyl ester of ganciclovir, was also found to inhibit ATB(0,+)-mediated glycine uptake competitively. Exposure of ATB(0,+)-expressing oocytes to glycine induced inward currents. Exposure to different valyl esters (methyl, butyl, and benzyl), benzyl esters of various neutral amino acids, and valganciclovir also induced inward currents in these oocytes. The current induced by valganciclovir was saturable with a K0.5 value of 3.1+/-0.7 mM and was obligatorily dependent on Na+ and Cl-. The Na+:Cl-:valganciclovir stoichiometry was 2 or 3:1:1. CONCLUSIONS: Amino acid esters and the amino-acid-based prodrug valganciclovir are transported by ATB(0,+). This shows that ATB(0,+) can serve as an effective delivery system for amino acid-based prodrugs.

Amino Acid Transport System ASC↗

PubMed2004

N-cyclohexanecarbonylpentadecylamine: a selective inhibitor of the acid amidase hydrolysing N-acylethanolamines, as a tool to distinguish acid amidase from fatty acid amide hydrolase.

Anandamide ( N-arachidonoylethanolamine) and other bioactive N-acylethanolamines are degraded to their corresponding fatty acids and ethanolamine. This hydrolysis is mostly attributed to catalysis by FAAH (fatty acid amide hydrolase), which exhibits an alkaline pH optimum. In addition, we have identified another amidase which catalyses the same reaction exclusively at acidic pH values [Ueda, Yamanaka and Yamamoto (2001) J. Biol. Chem. 276, 35552-35557]. In attempts to find selective inhibitors of this acid amidase, we screened various derivatives of palmitic acid, 1-hexadecanol, and 1-pentadecylamine with N-palmitoylethanolamine as substrate. Here we show that N-cyclohexanecarbonylpentadecylamine inhibits the acid amidase from rat lung with an IC50 of 4.5 microM, without inhibiting FAAH at concentrations up to 100 microM. The inhibition was reversible and non-competitive. This compound also inhibited the acid amidase in intact alveolar macrophages. With the aid of this inhibitor, it was revealed that rat basophilic leukaemia cells possess the acid amidase as well as FAAH. Thus the inhibitor may be a useful tool to distinguish the acid amidase from FAAH in various tissues and cells and to elucidate the physiological role of the enzyme.

Amides↗

PubMed1976

Plasma amino acids in reptiles after feeding protein or amino acids and after injecting amino acids.

Turtles (Pseudemys scripta elegans) and alligators (Alligator mississipiensis) were fed fish, casein, or free amino acid mixtures, or were injected with free amino acid mixtures, quantities in each case being equivalent to about 42 mmoles of amino acids/kg body weight. The experiments were designed to determine whether protein synthesis normally precedes catabolism of the amino acids absorbed from digesting food. Both animals disposed of free or food-derived amino acids more rapidly than could be accounted for by catabolism alone, but the transient increases in turtle plasma concentrations consisted mostly of essential amino acids, whereas the alligator plasma showed little increase in essential amino acids and considerable rises in four nonessential amino acids, glutamine, glutamic acid, glycine and alanine. Despite some species variation, these two species with low metabolic rates apparently utilized protein synthesis to dispose of amino acid mixtures prior to the necessarily slow process of catabolism for energy.

Administration, Oral↗

PubMed2007

Effect of omeprazole on acid gastroesophageal reflux and gastric acidity in preterm infants with pathological acid reflux.

INTRODUCTION: Proton pump inhibitor (PPI) therapy is increasingly being used to treat premature infants with gastroesophageal reflux disease (GERD); however, the efficacy of PPI on acid production in this population has yet to be assessed in this patient group. The aim of this study was to determine the effect of 0.7 mg/kg/d omeprazole on gastric acidity and acid gastroesophageal reflux in preterm infants with reflux symptoms and pathological acid reflux on 24-h pH probe. METHODS: A randomized, double blind, placebo-controlled, crossover design trial of omeprazole therapy was performed in 10 preterm infants (34-40 weeks postmenstrual age). Infants were given omeprazole for 7 d and then placebo for 7 d in randomized order. Twenty-four-hour esophageal and gastric pH monitoring was performed on days 7 and 14 of the trial. RESULTS: Compared to placebo, omeprazole therapy significantly reduced gastric acidity (%time pH <4, 54% vs 14%, P < 0.0005), esophageal acid exposure (%time pH <4, 19% vs 5%, P < 0.01) and number of acid GER episodes (119 vs 60 episodes, P < 0.05). CONCLUSIONS: Omeprazole is effective in reducing esophageal acid exposure in premature infants with pathological acid reflux on 24-h pH probe; however, the far more complex issues of safety and efficacy have yet to be addressed.

Anti-Ulcer Agents↗

PubMed1989

Synthesis of new bile acid analogues and their metabolism in the hamster: 3 alpha, 6 alpha-dihydroxy-6 beta-methyl-5 beta-cholanoic acid and 3 alpha, 6 beta-dihydroxy-6 alpha-methyl-5 beta-cholanoic acid.

This paper reports the chemical synthesis of two new bile acid analogues, namely, 3 alpha, 6 beta-dihydroxy-6 alpha-methyl-5 beta-cholanoic acid from 3 alpha-hydroxy-6-oxo-5 beta-cholanoic acid and describes their metabolism in the hamster. A Grignard reaction of the oxo acid with methyl magnesium iodide in tetrahydrofuran gave two epimeric dihydroxy-6-methyl-cholanoic acids which were separated as the methyl esters by silica gel column chromatography. The configuration of the 6-methyl groups was assigned by proton nuclear magnetic resonance spectroscopy and was supported by the chromatographic properties of the new compounds. The metabolism of the two new bile acid analogues was studied in the hamster. After intraduodenal administration of the 14C-labeled analogues into bile fistula hamsters, both compounds were absorbed rapidly from the intestine and secreted into bile. Intravenous infusion studies revealed that these compounds were efficiently extracted by the liver; the administered analogues became major biliary bile acids, present as either the glycine or taurine conjugates. These compounds are useful to study the effect of methyl-substituted bile acids on cholesterol and bile acid metabolism and may possibly possess cholelitholytic properties.

Animals↗

PubMed1982

Influence of fatty acids on the binding of calcium to human albumin. Correlation of binding and conformation studies and evidence for distinct differences between unsaturated fatty acids and saturated fatty acids.

The influence of various fatty acids of 14-18 carbon chain lengths on the binding of calcium to human serum albumin was studied. The cis-unsaturated fatty acids (myristoleic, palmitoleic, oleic, and linoleic) caused a much larger increase in the affinity and maximum binding of calcium for albumin than did saturated fatty acids (myristic, palmitic, and stearic). For the unsaturated fatty acids, the influence on calcium-albumin binding increased as the degree of unsaturation increased or the chain length decreased. With oleic or linoleic acid, increases in calcium binding were observed at approximately 2-3 mol of fatty acid/mol of albumin, while for myristic, palmitic, or elaidic acid, concentrations of 5-7 fatty acids/mol of albumin were required. The maximum fluorescence emission of albumin was found to change in parallel with the calcium binding for oleic, palmitic, and elaidic acids. We conclude that 1) cis-unsaturated and saturated or trans-unsaturated fatty acids have very different effects on the binding of calcium to human albumin, 2) the alteration in calcium binding is likely due to a conformational change in the albumin molecule, and 3) changes in calcium binding to albumin are observed at levels of cis-unsaturated fatty acids which are obtainable in vivo.

Binding Sites↗

PubMed1981

Synthesis of (22R and 22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acids and structure of haemulcholic acid, a unique bile acid isolated from fish bile.

(22R and 22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acids were synthesized, starting from chenodeoxycholic acid, in order to establish the chemical structure of haemulcholic acid, which has been found in certain fish as the major bile component. Oxidative decarboxylation of diformoxylated chenodeoxycholic acid with lead tetraacetate yielded 24-nor-5 beta-chol-22-ene-3 alpha, 7 alpha-diol, which was hydroxylated to form a mixture of (22R and 22S)-24-nor-5 beta-cholane-3 alpha, 7 alpha, 22,23-tetrols. Lead tetraacetate oxidation of the mixture yielded 3 alpha, 7 alpha-dihydroxy-23,24-dinor-5 beta-cholan-22-a1. A Reformatsky reaction of the dihydroxydinorcholanal with bromoacetate resulted in the formation of a mixture of (22R and 22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acids. The bile acids epimeric at C-22 were resolved by silica gel column chromatography, and their configurations of C-22 were assigned by a modification of Horeau's method and 13C-nuclear magnetic resonance spectroscopy. By direct comparison with synthetic bile acids, the naturally occurring haemulcholic acid was shown to be (22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acid.

Animals↗

PubMed2001

Infant plasma trans, n-6, and n-3 fatty acids and conjugated linoleic acids are related to maternal plasma fatty acids, length of gestation, and birth weight and length.

BACKGROUND: Arachidonic acid (AA) and docosahexaenoic acid (DHA) are important for growth and neural development. trans Fatty acids (TFAs) may inhibit desaturation of linoleic acid (LA) and alpha-linolenic acid (ALA) to AA and DHA, respectively. Conjugated linoleic acids (CLAs) also alter lipid metabolism and body fat. OBJECTIVE: We determined the associations of birth outcome with maternal and infant plasma concentrations of TFAs, CLAs, AA, and DHA. DESIGN: In healthy women, we sampled maternal blood at 35 wk gestation (n = 58) and umbilical cord blood at birth (n = 70). RESULTS: Mean (+/- SEM) TFA concentrations (% by wt) in infant plasma were as follows: triacylglycerol, 2.83 +/- 0.19 (range: 0.63-12.79); phospholipid, 0.67 +/- 0.03 (0.11-1.33); and cholesteryl ester, 2.04 +/- 0.01 (0.86-4.24). LA, AA, DHA, TFA, and CLA concentrations in infant phospholipids correlated with the same fatty acid in maternal plasma phospholipids (n = 44; P < 0.05). Infant plasma cholesteryl ester and triacylglycerol TFAs and cholesteryl ester CLAs (r = -0.33, -0.42, and -0.49, respectively) were significantly inversely related to length of gestation. Triacylglycerol and cholesteryl ester AA were positively related to length of gestation (r = 0.41 and 0.37, respectively) and birth weight (r = 0.27 and 0.23, respectively). Inverse correlations occurred between infant plasma TFA and DHA concentrations in triacylglycerols (r = -0.33) and between TFA and AA concentrations in cholesteryl esters (r = -0.23). CONCLUSION: The results suggest possible important effects of TFAs and of AA on fetal growth and length of gestation.

Arachidonic Acid↗

PubMed1980

Effects of biliary bile acid composition on biliary cholesterol saturation in gallstone patients treated with chenodeoxycholic acid and/or ursodeoxycholic acid.

Chenodeoxycholic acid (cheno) and ursodeoxycholic acid (urso) dissolve cholesterol gallstones in humans. In the present study conjugation of biliary bile acids with glycine and taurine and their effects on biliary cholesterol saturation were investigated during treatment with cheno, urso, and cheno-urso. Ten patients were included in this study, and every patient served as his own control. Each of the treatment periods lasted for 3 mo. During treatment with cheno or urso, daily doses of 11.9-15.6 mg/kg were administered, while during treatment with cheno-urso each bile acid was administered at one-half the dose. In the control period biliary bile acids consisted of 31.8 +/- 2.8% glycocheno, 10.9 +/- 1.2% taurocheno, 1.0 +/- 0.1% glycourso, and 0.3 +/- 0.1% taurourso. During the three treatment periods dihydroxy bile acids in bile and glycine conjugation of these dihydroxy bile acids increased significantly (P < 0.05). During treatment with urso the amounts of glycourso in bile were positively correlated to the dose of urso administered (P < 0.05). No correlation existed between urso dose and the amounts of taurourso in bile. Biliary cholesterol was 9.0 +/- 1.0 mol% in the control period and decreased during treatment with cheno, urso, and chenourso to 5.2 +/- 0.5, 3.7 +/- 0.3, and 3.8 +/- 0.3 mol%, respectively. Cholesterol saturation index corrected for the biliary content of glycourso and taurourso was 1.2 +/- 0.1 in the control period and decreased during treatment with cheno, urso, and cheno-urso to 0.8 +/- 0.1, 1.0 +/- 0.1 and 0.7 +/- 0.1, respectively. Thus urso treatment led to the lowest biliary content of cholesterol, but cheno-urso treatment led to significantly lower cholesterol saturation indices than urso treatment (P < 0.05).

Aged↗

PubMed1969