Branched-chain Carboxylic Acids Research Articles

Grouping of short alkyl-chain branched carboxylic acids for developmental toxicity

Read-across (RAx) and grouping of chemicals into categories are well-known concepts in toxicology. Recently, ECHA proposed a grouping approach for branched-chain carboxylic acids (BCAs) including more than 60 branched-chain saturated carboxylic acids for hazard identification. Grouping was based only on structural considerations. Due to developmental effects of two members, ECHA postulated that “all short carbon chain acids … are likely reproductive and developmental toxicants”. This work analyzes available data for BCAs. The number of compounds in the group can be significantly reduced by eliminating metal and organic salts of BCAs, compounds of unknown or variable composition, and complex reaction products or biological materials (UVCB compounds). For the resulting reduced number of compounds, grouping is supported by similar physicochemical data and expected similar biotransformation. However, analysis of adverse effects for compounds in the group and mechanistic information show that BCAs, as a class, do not cause developmental effects in rats. Rather, developmental toxicity is limited to selected BCAs with specific structures that share a common mode of action (histone deacetylase inhibition). Thus, the proposed grouping is unreasonably wide and the more detailed analyses show that structural similarity alone is not sufficient for grouping branched-chain carboxylic acids for developmental toxicity.

In Staphylococcus aureus, the acyl-CoA synthetase MbcS supports branched-chain fatty acid synthesis from carboxylic acid and aldehyde precursors.

In the human pathogen Staphylococcus aureus, branched-chain fatty acids (BCFAs) are the most abundant fatty acids in membrane phospholipids. Strains deficient for BCFAs synthesis experience auxotrophy in laboratory culture and attenuated virulence during infection. Furthermore, the membrane of S. aureus is among the main targets for antibiotic therapy. Therefore, determining the mechanisms involved in BCFAs synthesis is critical to manage S. aureus infections. Here, we report that the overexpression of SAUSA300_2542 (annotated to encode an acyl-CoA synthetase) restores BCFAs synthesis in strains lacking the canonical biosynthetic pathway catalyzed by the branched-chain α-keto acid dehydrogenase (BKDH) complex. We demonstrate that the acyl-CoA synthetase activity of MbcS activates branched-chain carboxylic acids (BCCAs), and is required by S. aureus to utilize the isoleucine derivative 2-methylbutyraldehyde to restore BCFAs synthesis in S. aureus. Based on the ability of some staphylococci to convert branched-chain aldehydes into their respective BCCAs and our findings demonstrating that branched-chain aldehydes are in fact BCFAs precursors, we propose that MbcS promotes the scavenging of exogenous BCCAs and mediates BCFA synthesis via a de novo alternative pathway.

Scientific Opinion on Flavouring Group Evaluation 7, Revision 6 (FGE.07Rev6): saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched-chain carboxylic acids from chemical group 5.

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 55 flavouring substances assigned to the Flavouring Group Evaluation 07 (FGE.07), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Fifty‐three substances have already been considered in FGE.07 and its revisions. This revision 6 includes two additional substances which have been cleared with respect to genotoxicity in FGE.201Rev2 (4‐methyl‐3‐hepten‐5‐one [FL‐no: 07.261]) and FGE.204Rev1 (non‐2‐en‐4‐one, [FL‐no: 07.187]). The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC) and available data on metabolism and toxicity. The Panel concluded that none of the 55 substances gives rise to safety concerns at their levels of dietary intake, when estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate. Normal and maximum use levels were available for all flavouring substances. For 52 substances, including the newly included substances [FL‐no: 07.187 and 07.261], their ‘modified Theoretical Added Maximum Daily Intakes’ (mTAMDIs) estimates were above the TTC for their structural classes (I and II). Therefore, for these 52 flavouring substances, more detailed data on uses and use levels should be provided to finalise their safety evaluations.

Reversible Neonatal Cholestasis Following In Utero Exposure to Valproic Acid

Valproic acid (VPA) is a branched-chain carboxylic acid with broad anticonvulsant activity. Its spectrum of activity is thought to be mediated by combined molecular effects on intercellular Na+ currents, neuron K+ channels, and inhibition of gamma-aminobutyric acid (GABA) transaminase (1,2). VPA is metabolized in the liver by cytochrome P-450 oxidase. Hepatotoxicity related to valproate therapy has been reported in certain individuals and appears to be caused by the accumulation of toxic metabolites, which may include 4-en-valproate (3). The hepatotoxicity has been ascribed to an inherited or acquired deficiency in the cytochrome P-450 enzyme-dependent beta-oxidation pathway, and is inducible by other drugs such as phenobarbital or phenytoin (4). Fatal hepatic failure can result, with a disproportionately large number of such cases observed in patients less than two years old with neurologic abnormalities, severe seizures, and multiple anti-epileptic drug therapy (3,5,6,7). However, neonatal hepatic toxicity in humans coincident with intrauterine VPA exposure has rarely been reported (8,9,10); these cases were never reversible, andconfounding etiologic variables could not be excluded. In pregnancy, VPA readily crosses the placenta and accumulates with fetal blood concentrations greater than those in the mother (11). It is a known human teratogen primarily associated with neural tube developmental defects such as spina bifida. A specific "fetal valproate syndrome," marked by fetal growth deficiency, developmental delay, and an increased incidence of craniofacial, cardiovascular, and digital abnormalities, has also been reported (1,3,12,13,14). Furthermore, a dose-dependent relationship in the occurrence of major malformations and minor anomalies has been suggested (15). Major malformations reported include persistent patent ductus arteriosus, trigonocephaly, aplasia of the first ribs, dysplasia of the sternum, meningomyelocele, aplasia of the radius, and congenital hip dislocation. Minor malformations included brachycephaly, dysmorphic facial features, long thin fingers, and inverted or accessory nipples. The teratogenic potential is thought to be mediated by a secondary zinc deficiency induced by complexing with VPA (16), as well as by inhibition of microsomal epoxide hydrolase (17), which may enhance the teratogenic potential of concomitant anticonvulsant therapy. Numerous animal models have been developed for the study of VPA. VPA has been shown to have equal teratogenic potential as trimethadione in mice (18). Skeletal abnormalities, delayed parturition, and postnatal growth (5) have been reported in both mice and rats receiving VPA. In addition, Paulson and Paulson (19) noted defects of the palate, eyes, heart, and limb buds in animal models. Animal models for a VPA-associated cholestasis, however, are lacking.

A comparative study on liquid phase equilibria of aqueous mixtures of two structurally close carboxylic acids with sec-amyl alcohols at 298.2 K

This research reports the results of measurements on liquid-liquid equilibrium (LLE) for the four ternary systems of (water + butyric or 3-methylbutyric acids + sec-amyl alcohol) and (water + butyric or 3-methylbutyric acids + sec-isoamyl alcohol) at 298.2 K and 0.1 MPa. According to the measured solubility and tie-line data, the related phase diagrams for the studied systems were plotted. Due to the strong structural similarity of the studied system's constituents, the influence of the chemical structures of the acids and the solvents on the LLE behavior was comparatively studied. The ternary systems display two forms of LLE phase diagrams. The aqueous systems of butyric acid and the two structural isomers (sec-amyl alcohol and sec-isoamyl alcohol) exhibit type-1 phase behavior of LLE, whereas the type-2 behavior was observed for the systems containing the branched chain carboxylic acid (3-methylbutyric acid). The activity coefficients models of UNIQUAC and NRTL fit the measured tie line-data. According to the measured LLE data, the values of the models' binary interaction parameters were optimized using MATLAB Fminsearch function. Based on the experimental data, the mass distribution coefficients and selectivity were evaluated and systematically compared for the studied systems. Finally, reliability of the obtained NRTL parameters was checked using topological analysis connected to the Gibbs tangent plane test.

A comparative study of liquid–liquid equilibria for aqueous mixtures of straight chain and branched chain carboxylic acids with methyl isobutyl carbinol

Liquid-liquid equilibrium (LLE) data of the (water + butyric or 3-methylbutyric acids + methyl isobutyl carbinol) ternary systems were experimentally obtained at T = (298.2, 303.2, and 308.2) K and P = 0.1 MPa for the first time. Using solubility and tie-line measurements, the triangle phase diagrams were obtained and influence of the chemical structure of the acids on the LLE behaviour was studied. The first ternary aqueous system containing butyric acid and the alcohol displays type-1 LLE behaviour, while the second one including 3-methylbutyric acid exhibits type-2 phase diagram. The reliability of the experimental data was checked using the Othmer-Tobias and Hand correlation equations. The UNIQUAC and NRTL thermodynamic models were used to fit the experimental tie line data and values of the corresponding binary interaction parameters were determined. The binary model parameters were optimized by the MATLAB fminsearch function. According to the experimental tie-line data, distribution coefficients and separation factors were determined for the studied systems.

Combination of type II fatty acid biosynthesis enzymes and thiolases supports a functional β-oxidation reversal

An engineered reversal of the β-oxidation cycle (r-BOX) and the fatty acid biosynthesis (FAB) pathway are promising biological platforms for advanced fuel and chemical production in part due to their iterative nature supporting the synthesis of various chain length products. While diverging in their carbon-carbon elongation reaction mechanism, iterative operation of each pathway relies on common chemical conversions (reduction, dehydration, and reduction) differing only in the attached moiety (acyl carrier protein (ACP) in FAB vs Coenzyme A in r-BOX). Given this similarity, we sought to determine whether FAB enzymes can be used in the context of r-BOX as a means of expanding available r-BOX components with a ubiquitous set of well characterized enzymes. Using enzymes from the type II FAB pathway (FabG, FabZ, and FabI) in conjunction with a thiolase catalyzing a non-decarboxylative condensation, we demonstrate that FAB enzymes support a functional r-BOX. Pathway operation with FAB enzymes was improved through computationally directed protein design to develop FabZ variants with amino acid substitutions designed to disrupt hydrogen bonding at the FabZ-ACP interface and introduce steric and electrostatic repulsion between the FabZ and ACP. FabZ with R126W and R121E substitutions resulted in improved carboxylic acid and alcohol production from one- and multiple-turn r-BOX compared to the wild-type enzyme. Furthermore, the ability for FAB enzymes to operate on functionalized intermediates was exploited to produce branched chain carboxylic acids through an r-BOX with functionalized priming. These results not only provide an expanded set of enzymes within the modular r-BOX pathway, but can also potentially expand the scope of products targeted through this pathway by operating with CoA intermediates containing various functional groups.

Utilization of multiple substrates by butyrate kinase from Listeria monocytogenes

Listeria monocytogenes, the causative agent of listeriosis, can build up to dangerous levels in refrigerated foods potentially leading to expensive product recalls. An important aspect of the bacterium's growth at low temperatures is its ability to increase the branched-chain fatty acid anteiso C15:0 content of its membrane at lower growth temperatures, which imparts greater membrane fluidity. Mutants in the branched-chain α-keto dehydrogenase (bkd) complex are deficient in branched-chain fatty acids (BCFAs,) but these can be restored by feeding C4 and C5 branched-chain carboxylic acids (BCCAs). This suggests the presence of an alternate pathway for production of acyl CoA precursors for fatty acid biosynthesis. We hypothesize that the alternate pathway is composed of butyrate kinase (buk) and phosphotransbutyrylase (ptb) encoded in the bkd complex which produce acyl CoA products by their sequential action through the metabolism of carboxylic acids. We determined the steady state kinetics of recombinant His-tagged Buk using 11 different straight-chain and BCCA substrates in the acyl phosphate forming direction. Buk demonstrated highest catalytic efficiency with pentanoate as the substrate. Low product formation observed with acetate (C2) and hexanoate (C6) as the substrates indicates that Buk is not involved in either acetate metabolism or long chain carboxylic acid activation. We were also able to show that Buk catalysis occurs through a ternary complex intermediate. Additionally, Buk demonstrates a strong preference for BCCAs at low temperatures. These results indicate that Buk may be involved in the activation and assimilation of exogenous carboxylic acids for membrane fatty acid biosynthesis.

Characterization of the Clostridium difficile volatile metabolome using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry.

Clostridium difficile is a bacterial pathogen capable of causing life-threatening infections of the gastrointestinal tract characterized by severe diarrhea. Exposure to certain classes of antibiotics, advanced age, and prolonged hospitalizations are known risk factors for infection by this organism. Anecdotally, healthcare providers have reported that they can smell C. difficile infections in their patients, and several studies have suggested that there may indeed be an olfactory signal associated with C. difficile-associated diarrhea. In this study, we sought to characterize the volatile molecules produced by an epidemic strain of C. difficile (R20291) using headspace solid-phase microextraction (HS-SPME) followed by two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS). We report on a set of 77 volatile compounds, of which 59 have not previously been associated with C. difficile growth in vitro. Amongst these reported compounds, we detect both straight-chain and branched-chain carboxylic acids, as well as p-cresol, which have been the primary foci of C. difficile volatile metabolomic studies to-date. We additionally report on novel sulfur-containing and carbonyl-containing molecules that have not previously been reported for C. difficile. With the identification of these novel C. difficile-associated volatile compounds, we demonstrate the superior resolution and sensitivity of GC×GC-TOFMS relative to traditional GC-MS.

Broad substrate specificity of phosphotransbutyrylase from Listeria monocytogenes: A potential participant in an alternative pathway for provision of acyl CoA precursors for fatty acid biosynthesis

Listeria monocytogenes, the causative organism of the serious food-borne disease listeriosis, has a membrane abundant in branched-chain fatty acids (BCFAs). BCFAs are normally biosynthesized from branched-chain amino acids via the activity of branched chain α-keto acid dehydrogenase (Bkd), and disruption of this pathway results in reduced BCFA content in the membrane. Short branched-chain carboxylic acids (BCCAs) added as media supplements result in incorporation of BCFAs arising from the supplemented BCCAs in the membrane of L. monocytogenes bkd mutant MOR401. High concentrations of the supplements also effect similar changes in the membrane of the wild type organism with intact bkd. Such carboxylic acids clearly act as fatty acid precursors, and there must be an alternative pathway resulting in the formation of their CoA thioester derivatives. Candidates for this are the enzymes phosphotransbutyrylase (Ptb) and butyrate kinase (Buk), the products of the first two genes of the bkd operon. Ptb from L. monocytogenes exhibited broad substrate specificity, a strong preference for branched-chain substrates, a lack of activity with acetyl CoA and hexanoyl CoA, and strict chain length preference (C3–C5). Ptb catalysis involved ternary complex formation. Additionally, Ptb could utilize unnatural branched-chain substrates such as 2-ethylbutyryl CoA, albeit with lower efficiency, consistent with a potential involvement of this enzyme in the conversion of the carboxylic acid additives into CoA primers for BCFA biosynthesis.

Valproic Acid versus Lamotrigine as First-line Monotherapy in Newly Diagnosed Idiopathic Generalized Tonic -Clonic Seizures in Adults - A Randomized Controlled Trial.

Idiopathic Generalized Tonic-Clonic Seizures (GTCS) are frequently encountered in adults. Their successful control is necessary to improve the quality of life of these patients. Valproic acid is a simple branched-chain carboxylic acid and lamotrigine is a phenyltriazine derivative. Opinions differ in regards to their effectiveness in idiopathic GTCS. To compare the effectiveness of valproic acid and lamotrigine in newly diagnosed adults with idiopathic generalized tonic-clonic seizures. The present prospective randomized study was conducted on 60 patients suffering from idiopathic GTCS. Thirty patients received valproic acid and rest 30 patients received lamotrigine. All patients were followed regularly monthly for one year for treatment response and adverse effects. After 12 months follow-up, 76.67% patients taking valproic acid and 56.67% patients taking lamotrigine were seizure-free. Common adverse effects recorded were nausea, dyspepsia, headache and skin rash. Valproic acid is more effective than lamotrigine as first-line drug in the treatment of adults with newly diagnosed idiopathic generalized tonic-clonic seizures.

Short branched-chain C6 carboxylic acids result in increased growth, novel ‘unnatural’ fatty acids and increased membrane fluidity in a Listeria monocytogenes branched-chain fatty acid-deficient mutant

Listeria monocytogenes is a psychrotolerant food borne pathogen, responsible for the high fatality disease listeriosis, and expensive food product recalls. Branched-chain fatty acids (BCFAs) of the membrane play a critical role in providing appropriate membrane fluidity and optimum membrane biophysics. The fatty acid composition of a BCFA-deficient mutant is characterized by high amounts of straight-chain fatty acids and even-numbered iso fatty acids, in contrast to the parent strain where odd-numbered anteiso fatty acids predominate. The presence of 2-methylbutyrate (C5) stimulated growth of the mutant at 37°C and restored growth at 10°C along with the content of odd-numbered anteiso fatty acids. The C6 branched-chain carboxylic acids 2-ethylbutyrate and 2-methylpentanoate also stimulated growth to a similar extent as 2-methylbutyrate. However, 3-methylpentanoate was ineffective in rescuing growth. 2-Ethylbutyrate and 2-methylpentanoate led to novel major fatty acids in the lipid profile of the membrane that were identified as 12-ethyltetradecanoic acid and 12-methylpentadecanoic acid respectively. Membrane anisotropy studies indicated that growth of strain MOR401 in the presence of these precursors increased its membrane fluidity to levels of the wild type. Cells supplemented with 2-methylpentanoate or 2-ethylbutyrate at 10°C shortened the chain length of novel fatty acids, thus showing homeoviscous adaptation. These experiments use the mutant as a tool to modulate the membrane fatty acid compositions through synthetic precursor supplementation, and show how existing enzymes in L. monocytogenes adapt to exhibit non-native activity yielding unique ‘unnatural’ fatty acid molecules, which nevertheless possess the correct biophysical properties for proper membrane function in the BCFA-deficient mutant.

Addition of Valproic Acid to CHO Cell Fed-Batch Cultures Improves Monoclonal Antibody Titers

Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. Cell line A responded highly positively, cell line B responded mildly positively, and cell line C did not respond. We then performed factorial experiments to identify the optimal VPA concentration and day of addition for cell line A. After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes.

Flavouring Group Evaluation 01 Rev2 (FGE.01 Rev2): Branched-chain aliphatic saturated aldehydes, carboxylic acids and related esters of primary alcohols and branched-chain carboxylic acids from chemical groups 1 and 2

Flavouring Group Evaluation 01 Rev2 (FGE.01 Rev2): Branched-chain aliphatic saturated aldehydes, carboxylic acids and related esters of primary alcohols and branched-chain carboxylic acids from chemical groups 1 and 2

Simultaneous Determination of Valproic Acid and its Toxic Metabolites, 4-ene-VPA and 2,4-diene-VPA in Rat Plasma using a Gas Chromatographic-mass Spectrometric Method

− A gas chromatographic-mass spectrometric (GC-MS) method was developed for the simultaneous determination of valproic acid (VPA) and its toxic metabolites, 4-ene-VPA and 2,4-diene-VPA in rat plasma. Extraction was performed in weak acidic condition (pH 5.2) to avoid degradation of 4-ene-VPA and 2,4-diene-VPA. The recoveries for 4-eneVPA and 2,4-diene-VPA were more than 70% and that for VPA was 33-42%. R value for each compounds exceeded 0.998 in calibration curve during all the analysis. Accuracy and precision ranged from 88.3 to 113.2% and from 2.16 to 14.2%, respectively The method was successfully applied to monitor plasma concentrations of VPA, 4-ene-VPA and 2,4-diene-VPA after intravenous administration of VPA at the dose of 100 mg/kg, suggesting that these toxic metabolites may involved in the hepatotoxicity induced by VPA. Key words− valproic acid (VPA), 4-ene-VPA, 2,4-diene-VPA, quantitative analysis, GC-MS (gas chromatographic-mass spectrometry), pharmacokinetics Valproic acid (VPA, 2-propylpentanoic acid, Fig. 1) is a broad-spectrum antiepileptic agent that has a branched-chain carboxylic acid structure. VPA has been used to treat bipolar disorder, migraine, and neuropathic pain (Loscher et al., 1993; Murakami et al., 1992; Sugimoto et al., 1983), but it has been demonstrated to be associated with fatal liver toxicity (Perucca, 2002; Zimmerman et al., 1982; Zafrani et al., 1982; Bryant et al., 1986). Although the mechanism by which VPA leads to liver toxicity has not been fully elucidated, a large body of evidence suggests that reactive VPA metabolites (4ene-VPA; 2-propyl-4-pentanoic acid and its subsequent metabolite, 2,4-diene-VPA; 2-propyl-2,4-pentanoic acid) may mediate the hepatotoxicity by inhibiting mitochondrial fatty acid β-oxidation (Zimmerman et al., 1982; Gerber et al., 1979; Kassahun et al., 1991). Therefore it is important to monitor the plasma concentration of 4-ene-VPA and 2,4diene-VPA as well as VPA itself to evaluate effect and toxicity of VPA. In order to monitor plasma concentration of VPA and its toxic metabolites, it is necessary to have reliable and sensitive method for the simultaneous quantitative determination of those compounds. Because of structural similarity between fatty acid (non polar compound) and VPA, most of analytical method for VPA and/or its metabolite has been used GC-MS (gas chromatography-mass spectrometry) (Fisher et al., 1992; Yu et al., 1995; Leis et al., 2003). But those reports did not focus on the toxic metabolites, 4-ene-VPA and 2,4-diene-VPA, so it is very hard to evaluate pharmacokinetics of VPA and its toxic metabolites. Recently the method using HPLC-MS/MS (high performance liquid chromatography-tandem mass spectrometry) was reported to analyze VPA, however this method was developed only for the quantification of VPA and 4-eneVPA. Thus it is also not adequate to monitor plasma concentrations of VPA and its toxic metabolites (Cheng et al., 2007). Moreover, sample extraction with organic solvent was performed in the pH condition less than pH 3, which was not favorable condition for 4-ene-VPA and 2,4-diene-VPA since they could be degraded in acidic condition. In this study we developed adequate method for the quantitative analysis of VPA, 4-ene-VPA and 2,4-diene-VPA in rat plasma. We used mild pH condition to prevent degradation of the metabolites. This analytical method was validated and applied to evaluate pharmacokinetics of VPA and its metabolites after intravenous administration to rats. Corresponding Author : Tel : +82-2-958-5062, E-mail : jbhluck@kist.re.kr DOI : 10.4333/KPS.2010.40.3.155 156 Min Sun Lee, Young-Joo Lee, Bong Chul Chung and Byung Hwa Jung J. Pharm. Invest., Vol. 40, No. 3 (2010) Experimental

Influence of fatty acid precursors, including food preservatives, on the growth and fatty acid composition of Listeria monocytogenes at 37 and 10degreesC.

Listeria monocytogenes is a food-borne pathogen that grows at refrigeration temperatures and increases its content of anteiso-C(15:0) fatty acid, which is believed to be a homeoviscous adaptation to ensure membrane fluidity, at these temperatures. As a possible novel approach for control of the growth of the organism, the influences of various fatty acid precursors, including branched-chain amino acids and branched- and straight-chain carboxylic acids, some of which are also well-established food preservatives, on the growth and fatty acid composition of the organism at 37 degrees C and 10 degrees C were studied in order to investigate whether the organism could be made to synthesize fatty acids that would result in impaired growth at low temperatures. The results indicate that the fatty acid composition of L. monocytogenes could be modulated by the feeding of branched-chain amino acid, C(4), C(5), and C(6) branched-chain carboxylic acid, and C(3) and C(4) straight-chain carboxylic acid fatty acid precursors, but the growth-inhibitory effects of several preservatives were independent of effects on fatty acid composition, which were minor in the case of preservatives metabolized via acetyl coenzyme A. The ability of a precursor to modify fatty acid composition was probably a reflection of the substrate specificities of the first enzyme, FabH, in the condensation of primers of fatty acid biosynthesis with malonyl acyl carrier protein.

Flavouring Group Evaluation 7, Revision 2 (FGE.07Rev2) : Saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched-chain carboxylic acids from chemical group 5

Flavouring Group Evaluation 7, Revision 2 (FGE.07Rev2) : Saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched-chain carboxylic acids from chemical group 5

Flavouring Group Evaluation 7, Revision 1 (FGE.07Rev1): Saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched-chain carboxylic acids from chemical group 5 (Commission Regulation (

Flavouring Group Evaluation 7, Revision 1 (FGE.07Rev1): Saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched-chain carboxylic acids from chemical group 5 (Commission Regulation (

Flavouring Group Evaluation 1, Revision 1 (FGE.01Rev 1): Branched-chain aliphatic saturated aldehydes, carboxylic acids and related esters of primary alcohols and branched-chain carboxylic acids from chemical groups 1 and 2 (Commission Regulation (EC) No

Flavouring Group Evaluation 1, Revision 1 (FGE.01Rev 1): Branched-chain aliphatic saturated aldehydes, carboxylic acids and related esters of primary alcohols and branched-chain carboxylic acids from chemical groups 1 and 2 (Commission Regulation (EC) No

Influence of the alkyl-chain on the symmetry and structural changes of Zn 4O(RCO 2) 6 complexes in film phase—An FT-IR study

The Zn 4O(RCO 2) 6 complexes of a selection of straight- and branched-chain carboxylic acids have been prepared in CCl 4 and characterized by their 13C NMR, 1H NMR and mid-FT-IR spectra. Their structural stability was studied by FT-IR-spectroscopy over a 4-day long period of time in CCl 4 solution and as cast films. The observed characteristic spectroscopic features have been discussed. The cast film samples showed extremely diverse behaviour from instant decomposition to the perfect conservation of the original T d symmetry, even though water was not excluded from the system. An explanation, supported by ab initio quantum chemical calculations on the conformation of the free carboxylate ions with various alkyl-chains, has been given for the diverse behaviour of the samples. Formation of a hydrocarbon moiety, with somewhat extended anti-periplanar (all- trans) conformation, perpendicular to the carboxylate plane was the essential factor in the preservation of the structure and the quaternary α-carbon was an additional requirement to sustain its symmetry. Two attempts at preparing the corresponding Zn 4O(RCO 2) 6 complexes from water have been successful in the cases when the R-groups fulfilled the requirements in geometry stated above.