R2(4hydroxyphenoxy)propionic acid(RHPPA)is a key intermediate for the synthesis of classic herbicides with high selectivity against grassy weed.The main route for RHPPA biosynthesis is to hydroxylate the substrate R2p...R2(4hydroxyphenoxy)propionic acid(RHPPA)is a key intermediate for the synthesis of classic herbicides with high selectivity against grassy weed.The main route for RHPPA biosynthesis is to hydroxylate the substrate R2phenoxypropionic acid(RPPA)at C4 position with microbes.In order to provide sufficient RPPA for the industrial production of RHPPA,an effective RPPA synthesis method was established and optimized in this work.The synthesis process mainly consisted of two steps:(1)synthesis of S2chloropropionic acid from Lalanine via diazotization and chlorination reactions;and(2)synthesis of RPPA from S2chloropropionic acid and phenol via etherification reaction.The optimal reaction conditions were as follows:HCl:NaNO_(2):KI:LAla=2.0:1.2:0.7:1.0(in molar),125℃reflux for 1.5 h,with KI as catalyst,and KI:S2chloropropionic acid:phenol=0.075:1.2:1.0(in molar).Under these conditions,an improved molar conversion rate(74.9%,calculated in phenol)was achieved.After extraction using anionic exchange resin Amberlite IRA400(CI),RPPA product with a purity of 95.08%was obtained.The purified RPPA was identified and evaluated in the application of the biotransformative production of RHPPA.The results indicated that the synthesized RPPA supported the RHPPA biosynthesis with a comparable yield as that of the standard RPPA.The RPPA synthesis method provided herein exhibited the advantages of low price and easy availability of raw materials,less toxicity of reagents,simple manipulations,and low equipment/instrument requirements.展开更多
Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for autism.Mitoch...Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for autism.Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate.Rat models of autism were established by intracerebroventricular injection of propionic acid.These rat models had memory dysfunction,decreased muscle coordination and gait imbalance.Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines,oxidative stress and lipid biomarkers.Oral administration of 10,20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner.These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism.This study was approved by the RITS/IAEC,SIRSA,HARYANA on March 3,2014(approval No.RITS/IAEC/2014/03/03).展开更多
A rapid and simple method is presented for determining β-N-oxalyl-α. β- diaminopropionic acid (β -ODAP) and its much less toxic α -isomer (α -ODAP) in Lathyrus sativus. Seed and foliage extracts of Lathyrus sati...A rapid and simple method is presented for determining β-N-oxalyl-α. β- diaminopropionic acid (β -ODAP) and its much less toxic α -isomer (α -ODAP) in Lathyrus sativus. Seed and foliage extracts of Lathyrus sativus were treated with 1-fluoro-2,4-dinitrobenzene (FDNB) and a reversed-phase high-performance liquid chromatographic method for the separation of the derivatives in the pmol range is reported.展开更多
Mild stir-assisted membrane dispersion extraction(MDE) method was employed to enhance propionic acid(HA)extraction and compared to the mechanical stirred extraction(MSE) method. Triocylamine(TOA) and tributyl phosphat...Mild stir-assisted membrane dispersion extraction(MDE) method was employed to enhance propionic acid(HA)extraction and compared to the mechanical stirred extraction(MSE) method. Triocylamine(TOA) and tributyl phosphate(TBP) were chosen as model extractant to extract HA. Firstly, droplet size and the size distribution of organic phase were analyzed, and then the effects of phase ratio, extractant and HA concentration on extraction performance were investigated. Comparing the two extraction methods, the results show mild stir-assisted MDE method reduced the mass transfer equilibrium time compared to MSE method. The mass transfer mechanism was explored by analyzing mass transfer resistance. Mild stir-assisted MDE had less total mass transfer resistance than MSE. When the extractant concentration was 40%, the extraction process was controlled by organic phase mass transfer process with HA volume fraction was 1% and controlled by both of reaction process and organic phase mass transfer process when HA concentration increased to 5%. This work may provide a new type of extraction method for the recovery of organic carboxylic acid.展开更多
S)-2-(6’-methoxyl-（-naphthyl） propionic acid （（S）-Naproxen, ee 99%） has been prepared starting from （6-methoxyl-α-naphthyl）propan-1-one and D-sorbitol under SmCl3 catalysis.
This paper reports on the resolution of(R,S)-2-(4-methylphenyl)propionic acid(MPPA)enantiomers by enzymatic esterification in organic solvent.Novozym 435(CALB)has the best catalytic performance compared with other lip...This paper reports on the resolution of(R,S)-2-(4-methylphenyl)propionic acid(MPPA)enantiomers by enzymatic esterification in organic solvent.Novozym 435(CALB)has the best catalytic performance compared with other lipases.Of the alcohols screened,n-hexanol is the best acyl acceptor and gives the highest enzyme activity and enantioselectivity in n-hexane.Response surface methodology(RSM)was used to evaluate the influence of the factors,such as temperature,enzyme amount,substrate concentration and reaction time on the substrate conversion(c)and enantiomeric excess(ee).The correlation coefficient R2 for enantiomeric excess and the conversion are 0.9827 and 0.9910,respectively,indicating that can accurately predict the experimental results.By simulation and optimization,the optimal conditions were obtained,involving 600 mmol·L^-1 MPPA concentration(0.60 mmol),850 mmol·L^-1 hexanol concentration(0.85 mmol),58 mg enzyme amount,75℃temperature and 4.5 h reaction time,respectively.Under the optimized conditions,the experimental values of conversion and enantiomeric excess were 89.34%and 97.84%,respectively,which are in good agreement with the model predictions.展开更多
BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple gen...BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple genetic disorders at once.Here,we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects(PGT-M)approach for detecting propionic acidemia(PA)in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit(PCCA)couple.CASE SUMMARY A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling.They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit(PCCB)genotype.Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant(c.2041-1G>T,ClinVar:RCV-000802701.1;dbSNP:rs1367867218)in both parents.The couple requested in vitro fertilization(IVF)and PGT-M for PA.From IVF,12 oocytes were collected and fertilized,of which two resulted in high-quality embryos.Trophectoderm biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were euploid.Endpoint polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female embryo.Both embryos were transferred,resulting in a clinical pregnancy and the delivery of a healthy male newborn(38 wk,weight:4080 g,length:49 cm,APGAR 9/9).The absence of PA was confirmed by expanded newborn screening.CONCLUSION We show that using PGT-M with Whole Genome Amplification templates,coupled with IVF,can reduce the transmission of a pathogenic variant of the PCCA gene.展开更多
One of the most common recessively inherited organic acidemias is the Propionic Acidosis (PA) which results from Propionyle-CoA Carboxylase (PCC) enzyme deficiency that is necessary for the catabolism of the branched ...One of the most common recessively inherited organic acidemias is the Propionic Acidosis (PA) which results from Propionyle-CoA Carboxylase (PCC) enzyme deficiency that is necessary for the catabolism of the branched chain Amino Acids and other metabolites. Classically this disease presented with high anion gap metabolic acidosis with its clinical consequences. We report 4 patients who presented to our facility with sepsis like picture and no metabolic acidosis. All of them were found to have high ammonia level. Diagnosis was confirmed by tandem MS/MS and urine Gas Chromatography/ Mass Spectrometry (GC/MS). All of them were treated supportively and by supplementation of adequate calories and PA formula. The different presentations may be very well attributed to the PCC molecular defects heterogeneity. Mutations in both genes PCCA and PCCB can cause PA with more frequent heterogeneity of PCCA gene. In spite of the fact that PCCB gene is responsible for the most of the oriental cases, our first patient condition was attributed to PCCA gene with a rare mutation which was not described in the literatures.展开更多
Propionic acidemia is an autosomal recessive disorder that is due to deficiency in the enzyme propionyl-CoA carboxylase. Cardiomyopathy is a well-known phenomenon in propionic acidemia that it may rapidly progress to ...Propionic acidemia is an autosomal recessive disorder that is due to deficiency in the enzyme propionyl-CoA carboxylase. Cardiomyopathy is a well-known phenomenon in propionic acidemia that it may rapidly progress to death. Here we describe a case of propionic acidemia in a 27-year-old man who developed adult-onset secondary dilated cardiomyopathy. In early infancy he was diagnosed with propionic acidemia and was later noted to have mild mental retardation, mild renal failure, and optic nerve atrophy. Although he was in good energy status with a low-protein diet and carnitine supplementation, he was admitted to our university hospital with decompensate heart failure, which resulted in low-output cardiac syndrome with massive mitral regurgitation and left ventricular dyssynchrony. Cardiac resynchronization therapy (CRT) and continuous hemodiafiltration followed by hemodialysis (HD) dramatically improved his clinical status.展开更多
The production and accumulation of propionic acid affect significantly anaerobic wastewater treatment system, but the reasons are not approached until now. Based on the results of continuous-flow tests and the analysi...The production and accumulation of propionic acid affect significantly anaerobic wastewater treatment system, but the reasons are not approached until now. Based on the results of continuous-flow tests and the analysis of biochemistry and ecology, two mechanisms of producing propionic acid have been put forward. It is demonstrated that the reasons of propionic acid production and accumulation are not caused by higher hydrogen partial pressure. The combination of specific pH value and ORP is the ecological factor affecting propionic acid production, and the equilibrium regulation of NADH/NAD+ ratio in cells is the physiological factor. Meanwhile, it is put forward that using the two-phase anaerobic treatment process and the ethanol type fermentation in anaerobic reactor to avoid propionic acid accumulation are efficient methods.展开更多
The sterically hindered condensation of β-triphenylgermanyl propionic acid withα-hydroxy phosphonic ester has been studied.The failure of conventional ways of the condensation is probablydue to the bulky groups Ph&l...The sterically hindered condensation of β-triphenylgermanyl propionic acid withα-hydroxy phosphonic ester has been studied.The failure of conventional ways of the condensation is probablydue to the bulky groups Ph<sub>3</sub>Ge-and-P（O）（OR）<sub>2</sub>.However,several novel O,O-dialkyl-α-（β-triphenylgermanyl）propionoxy phosphonic esters have been synthesized successfully in good yields by using DCC catalyzed bypyridine or HOBt.The reactivity has much to do with the steric hindrance of the groups R.Thelarger the OR,the slower the reaction rate is.All the new products were characterized by <sup>1</sup>H NMR,IRspectra,MS and elemental analyses.A single crystal A<sub>1</sub> was obtained and the structure was determined byX-ray diffraction.Preliminary bioassays showed that the new products exhibit antitumor activity.展开更多
Tertiary amines dissolved in diluents are attractive extractants for recovery of carboxylic acids from dilute aqueous solutions. Quantitative Fourier transform infrared (FTIR) analysis of organic solutions containing ...Tertiary amines dissolved in diluents are attractive extractants for recovery of carboxylic acids from dilute aqueous solutions. Quantitative Fourier transform infrared (FTIR) analysis of organic solutions containing various concentrations of trioctylamine (TOA), n octanol, and propionic acid was carried out, and liquid liquid equilibrium was investigated using TOA in n octanol as the solvent. The fraction of ion pair association between TOA and propionic acid in the organic phase was quantitatively determined by FTIR. The apparent reactive extraction equilibrium constant, K 11 , was calculated using the quantitative FTIR spectrum and the equilibrium data. The results show that the fraction of ion pair association depends on diluent concentration, complex dissolution for propionic acid, and association between TOA and propionic acid. The K 11 based on quantitative FTIR has the same loading trend as that from the equilibrium data.展开更多
3-(4-Phenyl) benzoyl propionic acid was used as the starting material for the synthesisof furanones (2), pyrrolinones (5), pyridazinones (7), benzoxazinones (8) and quinazolinones (9-11). The behaviour of the derivati...3-(4-Phenyl) benzoyl propionic acid was used as the starting material for the synthesisof furanones (2), pyrrolinones (5), pyridazinones (7), benzoxazinones (8) and quinazolinones (9-11). The behaviour of the derivatives of furanones and benzoxazinones toward different nucleophiles is reported.展开更多
Background:Propionic acidemia(PA)is caused by a deficiency of propionyl CoA carboxylase.A characteristic urine organic acid profile includes 3-hydroxypropionate,methylcitrate,tiglylglycine,and propionylglycine.The dia...Background:Propionic acidemia(PA)is caused by a deficiency of propionyl CoA carboxylase.A characteristic urine organic acid profile includes 3-hydroxypropionate,methylcitrate,tiglylglycine,and propionylglycine.The diagnosis of PA is confirmed by detection of mutations in the PCCA or PCCB genes.We herein report the clinical and molecular findings of four Thai patients with PA.Methods:Clinical findings of four Thai patients with PA were retrospectively reviewed.Urine organic acids were analyzed by gas chromatography-mass spectrometry.PCR-sequencing analyses of encoding exons and intron/exon boundaries of the PCCA and PCCB genes were performed.Results:All patients had neonatal onset of PA.One patient died of cardiomyopathy,and another one of pneumonia and metabolic decompensation.The remainder experienced significant neurocognitive impairment.Mutation analysis of the PCCA gene identified homozygous c.1284+1G>A in patient 1,c.230G>A(p.R77Q)and c.1855C>T(p.R619X)in patient 2,homozygous c.2125T>C(p.S709P)in patient 3,and only one mutant allele,c.231+1G>T in patient 4.No PCCB mutation was identified.Four mutations including c.230G>A,c.231+1G>T,c.1855C>T,and c.2125T>C have not been reported previously.Conclusions:The clinical and molecular study of these Thai patients provided additional knowledge of the genotype and phenotype characteristics of PA.The results of the study suggested that PCCA mutations in Asian populations were distinct from those of other populations.展开更多
BACKGROUND Alcoholism is regarded as a risk factor for vitamin B_(12)(VB_(12))deficiency.Because V B_(12) serves as a coenzyme of methylmalonyl-CoA mutase,a key enzyme in propionate metabolism,the ^(13)C-propionate br...BACKGROUND Alcoholism is regarded as a risk factor for vitamin B_(12)(VB_(12))deficiency.Because V B_(12) serves as a coenzyme of methylmalonyl-CoA mutase,a key enzyme in propionate metabolism,the ^(13)C-propionate breath test(PBT)has been studied as a non-invasive diagnostic modality for VB_(12) deficiency.However,the conventional PBT requires 2 h,which is inconvenient in clinical practice.We hypothesized that a faster PBT can be used to evaluate propionate metabolism and is more easily adaptable for clinical practice.AIM To evaluate a faster PBT for assessing the effects of long-term ethanol consumption on propionate metabolism in ethanol-fed rats(ERs).METHODS ERs were obtained by replacing standard drinking water(for control rats,CRs)with 16%ethanol solution in descendants of F344/DuCrj rats.Faster PBT was performed by administering ^(13)C-propionate aqueous solution to male and female ERs and CRs by inserting a metal tubule from the mouth to the stomach;exhaled gas was collected in a bag to measure its ^(13)CO_(2)/12CO_(2) isotope ratio via infrared isotope spectrometry.Serum VB_(12) and alanine transaminase(ALT)levels were measured via chemiluminescence immunoassay and the lactate dehydrogenaseultraviolet method,respectively.We evaluated statistical differences in mean body weight,change in ^(13)CO_(2)(Δ^(13)CO_(2)‰),peakΔ^(13)CO_(2)‰,and serum VB_(12) and ALT,between males and females and between ERs and CRs using the t-test and Mann-Whitney U test for normally and non-normally distributed variables,respectively.RESULTS Males weighed significantly more than females(P<0.001);CRs weighed significantly more than ERs(P<0.008).Δ^(13)CO_(2) reached a peak(C_(max))at 20 min and 30 min in females and males,respectively,decreasing after 20-30 min without rebound in all groups.Males had significantly higher C_(max) andΔ^(13)CO_(2) at 15-45 min than females(P<0.05;for all pairs).Propionate metabolism was enhanced in male ERs relative to male CRs,whereas metabolism did not differ markedly between ERs and CRs for females.Males had higher serum VB_(12) levels than females,without prominent differences between the ER and CR groups.Male CRs had notably higher ALT levels than male ERs.Thus,chronic ethanol consumption may trigger fatty acid production via intestinal bacteria and changes in gut microbiome composition.CONCLUSION Faster PBT shows that 16%ethanol consumption promotes propionate metabolism without inducing liver injury.This PBT may be used clinically to evaluate gut flora status.展开更多
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic fai...BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the- counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractable pruritus that developed shortly after taking naproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS: Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.展开更多
<strong>Introduction: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) use is very common. NSAIDs use could be associated with elevated eosinophil count which could be a class effect or patient-rela...<strong>Introduction: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) use is very common. NSAIDs use could be associated with elevated eosinophil count which could be a class effect or patient-related. Inflammation could be the link between NSAIDs use and eosinophilia. <strong>Aims: </strong>To compare the pattern of eosinophil count in the peripheral blood of frequent users of NSAIDs and healthy controls. <strong>Methodology: </strong>Two hundred (one hundred frequent users of NSAIDs and 100 healthy controls) participants who had no known risk factor for kidney disease and had given informed consent were recruited. Blood was taken to determine the white cell count and differentials, serum electrolyte and creatinine, and random blood sugar. <strong>Results:</strong> The mean age of NSAIDs users was not significantly different from controls, P = 0.3. The mean eosinophil count was higher in males than females. The incidence of eosinophilia in NSAIDs users was 4%. The mean Eosinophil count of NSAIDs users was insignificantly higher than controls, 164.3 ± 51 6 vs 135. 6 ± 53.4, P = 0.4. The mean platelet count of NSAIDs users was significantly higher compared to controls, P = 0.04. The mean hematocrit of NSAIDs users was significantly lower than the controls, P = 0.02. Propionic acid derivatives were associated with the highest eosinophil count. Eosinophil count was positively related to age and serum creatinine and inversely related to blood glucose, hematocrit and glomerular filtration rate.<strong> Conclusion: </strong>The incidence of eosinophilia was 4%. The eosinophil count was higher in frequent NSAIDs users than occasional and non-users, in males than females and with use propionic acid derivatives compared to other NSAIDs. The Eosinophil count was positively related to age and platelet count. Being commoner in inflammatory states, the tissue destruction associated with elevated EC can be avoided by the prevention and prompt treatment of inflammatory conditions.展开更多
The metabolic fate of 1 -nitropropane （1-NP） has not been previously reported. In this study male rats and chimpanzees were given single doses of 40 mg/kg ip and 5 mg/kg iv 1-[1-<sup>14</sup>C]NP, respec...The metabolic fate of 1 -nitropropane （1-NP） has not been previously reported. In this study male rats and chimpanzees were given single doses of 40 mg/kg ip and 5 mg/kg iv 1-[1-<sup>14</sup>C]NP, respectively. The quantitative extent of urinary and fecal elimination was similar in both species. The rats excreted 16.5% ofthedosein urine and 1.7% in feces. For chimpanzees the respective values were 14.8 and 1.2%. Experiments with rats demonstrated that the major route of elimination was by exhalation. With a total elimination via the lungs of 72.6%, rats expired 10.3% of the dose as unchanged 1-NP. Five polar metabolites were isolated from the urine of chimpanzees. The two major metabolites were identified as 3-hydroxypropionic acid and 7V-methyl-N-2-（methylsulfinyl）ethylpropionic acid amide （NMPA）. Both substances were also excreted in rat urine. The two identified metabolites indicate that 1-NP was degraded to propionic acid, part of which was modified to 3-hydroxypropionic acid or NMPA. A hypothetical pathway for the biochemical generation of NMPA is suggested.（c）1989 Academic Press, Inc.展开更多
The formation and breaking of intramolecular hydrogen bondsof bilirubin in CDCl<sub>3</sub>-DMSO-d<sub>6</sub> binary solvent have been investigated by meansof NMR spectroscopy.The chemical shi...The formation and breaking of intramolecular hydrogen bondsof bilirubin in CDCl<sub>3</sub>-DMSO-d<sub>6</sub> binary solvent have been investigated by meansof NMR spectroscopy.The chemical shifts of protons at dipyrrinone lactam C=Oand N-H,Pyrrole N-H,C-5,C-15 and methylene groups of 8,12-propionic acidside-chains changed markedly as a function of composition of the binarysolvent.The hydrogen bond formation is dependent on the conformation ofpropionic acid side-chains.展开更多
Vapor phase carbonylation of ethanol with Ni/C and Ni-Zn/C catalyst was investigatedunder atmospheric pressure.Ni-Zn/C was found to have a significantly higher activity andselectivity than Ni/C.Effects of Zn and Ni lo...Vapor phase carbonylation of ethanol with Ni/C and Ni-Zn/C catalyst was investigatedunder atmospheric pressure.Ni-Zn/C was found to have a significantly higher activity andselectivity than Ni/C.Effects of Zn and Ni loading on ethanol conversion and productdistributions were also investigated,and the sequence of metal loading was compared.The cata-lyst was characterized by XRD（X-ray diffraction）and SEM-EDS.The spectra of XRDdemonstrated that the catalyst structure was changed from crystalline to non-crystalline in theprocess of carbonylation.Stable iodide compound was formed due to the interaction betweenC<sub>2</sub>H<sub>5</sub>I and active metals.The authors believe that the active phase of carbonylation might havebeen non-crystalline.展开更多
文摘R2(4hydroxyphenoxy)propionic acid(RHPPA)is a key intermediate for the synthesis of classic herbicides with high selectivity against grassy weed.The main route for RHPPA biosynthesis is to hydroxylate the substrate R2phenoxypropionic acid(RPPA)at C4 position with microbes.In order to provide sufficient RPPA for the industrial production of RHPPA,an effective RPPA synthesis method was established and optimized in this work.The synthesis process mainly consisted of two steps:(1)synthesis of S2chloropropionic acid from Lalanine via diazotization and chlorination reactions;and(2)synthesis of RPPA from S2chloropropionic acid and phenol via etherification reaction.The optimal reaction conditions were as follows:HCl:NaNO_(2):KI:LAla=2.0:1.2:0.7:1.0(in molar),125℃reflux for 1.5 h,with KI as catalyst,and KI:S2chloropropionic acid:phenol=0.075:1.2:1.0(in molar).Under these conditions,an improved molar conversion rate(74.9%,calculated in phenol)was achieved.After extraction using anionic exchange resin Amberlite IRA400(CI),RPPA product with a purity of 95.08%was obtained.The purified RPPA was identified and evaluated in the application of the biotransformative production of RHPPA.The results indicated that the synthesized RPPA supported the RHPPA biosynthesis with a comparable yield as that of the standard RPPA.The RPPA synthesis method provided herein exhibited the advantages of low price and easy availability of raw materials,less toxicity of reagents,simple manipulations,and low equipment/instrument requirements.
文摘Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for autism.Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate.Rat models of autism were established by intracerebroventricular injection of propionic acid.These rat models had memory dysfunction,decreased muscle coordination and gait imbalance.Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines,oxidative stress and lipid biomarkers.Oral administration of 10,20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner.These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism.This study was approved by the RITS/IAEC,SIRSA,HARYANA on March 3,2014(approval No.RITS/IAEC/2014/03/03).
基金Tshe prOject!(39770469) supported by the National Natural Science Foundation of China.
文摘A rapid and simple method is presented for determining β-N-oxalyl-α. β- diaminopropionic acid (β -ODAP) and its much less toxic α -isomer (α -ODAP) in Lathyrus sativus. Seed and foliage extracts of Lathyrus sativus were treated with 1-fluoro-2,4-dinitrobenzene (FDNB) and a reversed-phase high-performance liquid chromatographic method for the separation of the derivatives in the pmol range is reported.
基金Supported by the Chinese High Technology Research and Development Program(2015CB251402,17-163-12-ZD-001-013-01)the National Natural Science Foundation of China(21676215,21676273,U1507203)+3 种基金China Petroleum Enterprise Cooperation Project(PRIKY17094)China Postdoctoral Science Foundation(2018M633556)the Youth Innovation Promotion Association,CAS(2016043)the Shaanxi Provincial Science Foundation(2017SF-201,2018JQ2052).
文摘Mild stir-assisted membrane dispersion extraction(MDE) method was employed to enhance propionic acid(HA)extraction and compared to the mechanical stirred extraction(MSE) method. Triocylamine(TOA) and tributyl phosphate(TBP) were chosen as model extractant to extract HA. Firstly, droplet size and the size distribution of organic phase were analyzed, and then the effects of phase ratio, extractant and HA concentration on extraction performance were investigated. Comparing the two extraction methods, the results show mild stir-assisted MDE method reduced the mass transfer equilibrium time compared to MSE method. The mass transfer mechanism was explored by analyzing mass transfer resistance. Mild stir-assisted MDE had less total mass transfer resistance than MSE. When the extractant concentration was 40%, the extraction process was controlled by organic phase mass transfer process with HA volume fraction was 1% and controlled by both of reaction process and organic phase mass transfer process when HA concentration increased to 5%. This work may provide a new type of extraction method for the recovery of organic carboxylic acid.
文摘S)-2-(6’-methoxyl-（-naphthyl） propionic acid （（S）-Naproxen, ee 99%） has been prepared starting from （6-methoxyl-α-naphthyl）propan-1-one and D-sorbitol under SmCl3 catalysis.
基金supported by the National Natural Science Foundation of China(21676077)。
文摘This paper reports on the resolution of(R,S)-2-(4-methylphenyl)propionic acid(MPPA)enantiomers by enzymatic esterification in organic solvent.Novozym 435(CALB)has the best catalytic performance compared with other lipases.Of the alcohols screened,n-hexanol is the best acyl acceptor and gives the highest enzyme activity and enantioselectivity in n-hexane.Response surface methodology(RSM)was used to evaluate the influence of the factors,such as temperature,enzyme amount,substrate concentration and reaction time on the substrate conversion(c)and enantiomeric excess(ee).The correlation coefficient R2 for enantiomeric excess and the conversion are 0.9827 and 0.9910,respectively,indicating that can accurately predict the experimental results.By simulation and optimization,the optimal conditions were obtained,involving 600 mmol·L^-1 MPPA concentration(0.60 mmol),850 mmol·L^-1 hexanol concentration(0.85 mmol),58 mg enzyme amount,75℃temperature and 4.5 h reaction time,respectively.Under the optimized conditions,the experimental values of conversion and enantiomeric excess were 89.34%and 97.84%,respectively,which are in good agreement with the model predictions.
文摘BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple genetic disorders at once.Here,we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects(PGT-M)approach for detecting propionic acidemia(PA)in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit(PCCA)couple.CASE SUMMARY A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling.They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit(PCCB)genotype.Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant(c.2041-1G>T,ClinVar:RCV-000802701.1;dbSNP:rs1367867218)in both parents.The couple requested in vitro fertilization(IVF)and PGT-M for PA.From IVF,12 oocytes were collected and fertilized,of which two resulted in high-quality embryos.Trophectoderm biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were euploid.Endpoint polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female embryo.Both embryos were transferred,resulting in a clinical pregnancy and the delivery of a healthy male newborn(38 wk,weight:4080 g,length:49 cm,APGAR 9/9).The absence of PA was confirmed by expanded newborn screening.CONCLUSION We show that using PGT-M with Whole Genome Amplification templates,coupled with IVF,can reduce the transmission of a pathogenic variant of the PCCA gene.
文摘One of the most common recessively inherited organic acidemias is the Propionic Acidosis (PA) which results from Propionyle-CoA Carboxylase (PCC) enzyme deficiency that is necessary for the catabolism of the branched chain Amino Acids and other metabolites. Classically this disease presented with high anion gap metabolic acidosis with its clinical consequences. We report 4 patients who presented to our facility with sepsis like picture and no metabolic acidosis. All of them were found to have high ammonia level. Diagnosis was confirmed by tandem MS/MS and urine Gas Chromatography/ Mass Spectrometry (GC/MS). All of them were treated supportively and by supplementation of adequate calories and PA formula. The different presentations may be very well attributed to the PCC molecular defects heterogeneity. Mutations in both genes PCCA and PCCB can cause PA with more frequent heterogeneity of PCCA gene. In spite of the fact that PCCB gene is responsible for the most of the oriental cases, our first patient condition was attributed to PCCA gene with a rare mutation which was not described in the literatures.
文摘Propionic acidemia is an autosomal recessive disorder that is due to deficiency in the enzyme propionyl-CoA carboxylase. Cardiomyopathy is a well-known phenomenon in propionic acidemia that it may rapidly progress to death. Here we describe a case of propionic acidemia in a 27-year-old man who developed adult-onset secondary dilated cardiomyopathy. In early infancy he was diagnosed with propionic acidemia and was later noted to have mild mental retardation, mild renal failure, and optic nerve atrophy. Although he was in good energy status with a low-protein diet and carnitine supplementation, he was admitted to our university hospital with decompensate heart failure, which resulted in low-output cardiac syndrome with massive mitral regurgitation and left ventricular dyssynchrony. Cardiac resynchronization therapy (CRT) and continuous hemodiafiltration followed by hemodialysis (HD) dramatically improved his clinical status.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 59578021) the National Distinguished Young Scientists Fund of China.
文摘The production and accumulation of propionic acid affect significantly anaerobic wastewater treatment system, but the reasons are not approached until now. Based on the results of continuous-flow tests and the analysis of biochemistry and ecology, two mechanisms of producing propionic acid have been put forward. It is demonstrated that the reasons of propionic acid production and accumulation are not caused by higher hydrogen partial pressure. The combination of specific pH value and ORP is the ecological factor affecting propionic acid production, and the equilibrium regulation of NADH/NAD+ ratio in cells is the physiological factor. Meanwhile, it is put forward that using the two-phase anaerobic treatment process and the ethanol type fermentation in anaerobic reactor to avoid propionic acid accumulation are efficient methods.
基金the National Natural Science Foundation of China.
文摘The sterically hindered condensation of β-triphenylgermanyl propionic acid withα-hydroxy phosphonic ester has been studied.The failure of conventional ways of the condensation is probablydue to the bulky groups Ph<sub>3</sub>Ge-and-P（O）（OR）<sub>2</sub>.However,several novel O,O-dialkyl-α-（β-triphenylgermanyl）propionoxy phosphonic esters have been synthesized successfully in good yields by using DCC catalyzed bypyridine or HOBt.The reactivity has much to do with the steric hindrance of the groups R.Thelarger the OR,the slower the reaction rate is.All the new products were characterized by <sup>1</sup>H NMR,IRspectra,MS and elemental analyses.A single crystal A<sub>1</sub> was obtained and the structure was determined byX-ray diffraction.Preliminary bioassays showed that the new products exhibit antitumor activity.
基金the National Natural Science Foundationof China(No. 2 9836 130 )
文摘Tertiary amines dissolved in diluents are attractive extractants for recovery of carboxylic acids from dilute aqueous solutions. Quantitative Fourier transform infrared (FTIR) analysis of organic solutions containing various concentrations of trioctylamine (TOA), n octanol, and propionic acid was carried out, and liquid liquid equilibrium was investigated using TOA in n octanol as the solvent. The fraction of ion pair association between TOA and propionic acid in the organic phase was quantitatively determined by FTIR. The apparent reactive extraction equilibrium constant, K 11 , was calculated using the quantitative FTIR spectrum and the equilibrium data. The results show that the fraction of ion pair association depends on diluent concentration, complex dissolution for propionic acid, and association between TOA and propionic acid. The K 11 based on quantitative FTIR has the same loading trend as that from the equilibrium data.
基金Permanent address:Chemistry Department,Faculty of Science,Fayoum,Cairo University,Egypt.
文摘3-(4-Phenyl) benzoyl propionic acid was used as the starting material for the synthesisof furanones (2), pyrrolinones (5), pyridazinones (7), benzoxazinones (8) and quinazolinones (9-11). The behaviour of the derivatives of furanones and benzoxazinones toward different nucleophiles is reported.
文摘Background:Propionic acidemia(PA)is caused by a deficiency of propionyl CoA carboxylase.A characteristic urine organic acid profile includes 3-hydroxypropionate,methylcitrate,tiglylglycine,and propionylglycine.The diagnosis of PA is confirmed by detection of mutations in the PCCA or PCCB genes.We herein report the clinical and molecular findings of four Thai patients with PA.Methods:Clinical findings of four Thai patients with PA were retrospectively reviewed.Urine organic acids were analyzed by gas chromatography-mass spectrometry.PCR-sequencing analyses of encoding exons and intron/exon boundaries of the PCCA and PCCB genes were performed.Results:All patients had neonatal onset of PA.One patient died of cardiomyopathy,and another one of pneumonia and metabolic decompensation.The remainder experienced significant neurocognitive impairment.Mutation analysis of the PCCA gene identified homozygous c.1284+1G>A in patient 1,c.230G>A(p.R77Q)and c.1855C>T(p.R619X)in patient 2,homozygous c.2125T>C(p.S709P)in patient 3,and only one mutant allele,c.231+1G>T in patient 4.No PCCB mutation was identified.Four mutations including c.230G>A,c.231+1G>T,c.1855C>T,and c.2125T>C have not been reported previously.Conclusions:The clinical and molecular study of these Thai patients provided additional knowledge of the genotype and phenotype characteristics of PA.The results of the study suggested that PCCA mutations in Asian populations were distinct from those of other populations.
基金the Japan Society for the Promotion of Science KAKENHI Grant, No. JP21K18089
文摘BACKGROUND Alcoholism is regarded as a risk factor for vitamin B_(12)(VB_(12))deficiency.Because V B_(12) serves as a coenzyme of methylmalonyl-CoA mutase,a key enzyme in propionate metabolism,the ^(13)C-propionate breath test(PBT)has been studied as a non-invasive diagnostic modality for VB_(12) deficiency.However,the conventional PBT requires 2 h,which is inconvenient in clinical practice.We hypothesized that a faster PBT can be used to evaluate propionate metabolism and is more easily adaptable for clinical practice.AIM To evaluate a faster PBT for assessing the effects of long-term ethanol consumption on propionate metabolism in ethanol-fed rats(ERs).METHODS ERs were obtained by replacing standard drinking water(for control rats,CRs)with 16%ethanol solution in descendants of F344/DuCrj rats.Faster PBT was performed by administering ^(13)C-propionate aqueous solution to male and female ERs and CRs by inserting a metal tubule from the mouth to the stomach;exhaled gas was collected in a bag to measure its ^(13)CO_(2)/12CO_(2) isotope ratio via infrared isotope spectrometry.Serum VB_(12) and alanine transaminase(ALT)levels were measured via chemiluminescence immunoassay and the lactate dehydrogenaseultraviolet method,respectively.We evaluated statistical differences in mean body weight,change in ^(13)CO_(2)(Δ^(13)CO_(2)‰),peakΔ^(13)CO_(2)‰,and serum VB_(12) and ALT,between males and females and between ERs and CRs using the t-test and Mann-Whitney U test for normally and non-normally distributed variables,respectively.RESULTS Males weighed significantly more than females(P<0.001);CRs weighed significantly more than ERs(P<0.008).Δ^(13)CO_(2) reached a peak(C_(max))at 20 min and 30 min in females and males,respectively,decreasing after 20-30 min without rebound in all groups.Males had significantly higher C_(max) andΔ^(13)CO_(2) at 15-45 min than females(P<0.05;for all pairs).Propionate metabolism was enhanced in male ERs relative to male CRs,whereas metabolism did not differ markedly between ERs and CRs for females.Males had higher serum VB_(12) levels than females,without prominent differences between the ER and CR groups.Male CRs had notably higher ALT levels than male ERs.Thus,chronic ethanol consumption may trigger fatty acid production via intestinal bacteria and changes in gut microbiome composition.CONCLUSION Faster PBT shows that 16%ethanol consumption promotes propionate metabolism without inducing liver injury.This PBT may be used clinically to evaluate gut flora status.
文摘BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the- counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractable pruritus that developed shortly after taking naproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS: Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.
文摘<strong>Introduction: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) use is very common. NSAIDs use could be associated with elevated eosinophil count which could be a class effect or patient-related. Inflammation could be the link between NSAIDs use and eosinophilia. <strong>Aims: </strong>To compare the pattern of eosinophil count in the peripheral blood of frequent users of NSAIDs and healthy controls. <strong>Methodology: </strong>Two hundred (one hundred frequent users of NSAIDs and 100 healthy controls) participants who had no known risk factor for kidney disease and had given informed consent were recruited. Blood was taken to determine the white cell count and differentials, serum electrolyte and creatinine, and random blood sugar. <strong>Results:</strong> The mean age of NSAIDs users was not significantly different from controls, P = 0.3. The mean eosinophil count was higher in males than females. The incidence of eosinophilia in NSAIDs users was 4%. The mean Eosinophil count of NSAIDs users was insignificantly higher than controls, 164.3 ± 51 6 vs 135. 6 ± 53.4, P = 0.4. The mean platelet count of NSAIDs users was significantly higher compared to controls, P = 0.04. The mean hematocrit of NSAIDs users was significantly lower than the controls, P = 0.02. Propionic acid derivatives were associated with the highest eosinophil count. Eosinophil count was positively related to age and serum creatinine and inversely related to blood glucose, hematocrit and glomerular filtration rate.<strong> Conclusion: </strong>The incidence of eosinophilia was 4%. The eosinophil count was higher in frequent NSAIDs users than occasional and non-users, in males than females and with use propionic acid derivatives compared to other NSAIDs. The Eosinophil count was positively related to age and platelet count. Being commoner in inflammatory states, the tissue destruction associated with elevated EC can be avoided by the prevention and prompt treatment of inflammatory conditions.
文摘The metabolic fate of 1 -nitropropane （1-NP） has not been previously reported. In this study male rats and chimpanzees were given single doses of 40 mg/kg ip and 5 mg/kg iv 1-[1-<sup>14</sup>C]NP, respectively. The quantitative extent of urinary and fecal elimination was similar in both species. The rats excreted 16.5% ofthedosein urine and 1.7% in feces. For chimpanzees the respective values were 14.8 and 1.2%. Experiments with rats demonstrated that the major route of elimination was by exhalation. With a total elimination via the lungs of 72.6%, rats expired 10.3% of the dose as unchanged 1-NP. Five polar metabolites were isolated from the urine of chimpanzees. The two major metabolites were identified as 3-hydroxypropionic acid and 7V-methyl-N-2-（methylsulfinyl）ethylpropionic acid amide （NMPA）. Both substances were also excreted in rat urine. The two identified metabolites indicate that 1-NP was degraded to propionic acid, part of which was modified to 3-hydroxypropionic acid or NMPA. A hypothetical pathway for the biochemical generation of NMPA is suggested.（c）1989 Academic Press, Inc.
文摘The formation and breaking of intramolecular hydrogen bondsof bilirubin in CDCl<sub>3</sub>-DMSO-d<sub>6</sub> binary solvent have been investigated by meansof NMR spectroscopy.The chemical shifts of protons at dipyrrinone lactam C=Oand N-H,Pyrrole N-H,C-5,C-15 and methylene groups of 8,12-propionic acidside-chains changed markedly as a function of composition of the binarysolvent.The hydrogen bond formation is dependent on the conformation ofpropionic acid side-chains.
基金Supported by the Guangdong Provincial Naturial Science Foundation of China.
文摘Vapor phase carbonylation of ethanol with Ni/C and Ni-Zn/C catalyst was investigatedunder atmospheric pressure.Ni-Zn/C was found to have a significantly higher activity andselectivity than Ni/C.Effects of Zn and Ni loading on ethanol conversion and productdistributions were also investigated,and the sequence of metal loading was compared.The cata-lyst was characterized by XRD（X-ray diffraction）and SEM-EDS.The spectra of XRDdemonstrated that the catalyst structure was changed from crystalline to non-crystalline in theprocess of carbonylation.Stable iodide compound was formed due to the interaction betweenC<sub>2</sub>H<sub>5</sub>I and active metals.The authors believe that the active phase of carbonylation might havebeen non-crystalline.
