SEARCH · PubMed Health
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.
A simple and accurate method for the extraction and quantitative estimation of individual, volatile free fatty acids of human blood is described. Values in normal serum, plasma, and red cells are given. Besides acetic and propionic, normal and isobutyric and isovaleric acids have been found.
Cultures of Tetrahymena pyriformis were incubated for 1 hour with a mixture of acetate, pyruvate, and pentanoate with only one substrate labeled at a time and with the position of the label chosen so that [1-14-C]acetyl coenzyme A was an early product of the metabolism of each substrate. The appearance of label in CO2, lipids, glycogen, glutamate, and alanine were measured and results interpreted in terms of a previously developed three-compartment model of metabolism, which was found to quantitatively describe the data even when two of the flux rates (the flux of acetyl-CoA from the peroxisomal to the outer mitochondrial compartment and from the outer mitrochondrial to the inner mitochondrial compartment) were set equal to zero. This reduction in the number of independent parameters leads to the model being overdetermined and to a probably unique fit of the three-compartment model tof the present data and to previous data when octanoate was the fatty acid substrate. Pentanoate was metabolized to a greater extent than octanoate and did not inhibit growth. Pentanoate inhibited acetate utilization in both the inner mitochondrial and peroxisomal compartments as indicated by a reduction in the incorporation of label from [1-14-C]acetate into lipids and into CO2, but there was no difference in oxidation of [2-14-C]pyruvate when pentanoate was the fatty acid substrate as compared to octanoate. Glyconeogenesis was inhibited when pentanoate was substituted for octanoate. Similar experiments were performed on cells treated with 4-pentenoic acid. The effects of 4-pentenoic acid were essentially the same whether octanoate or pentanoate was the fatty acid substrate, i.e. inhibition of glyconeogenesis from all labeled substrates and inhibition of [2-14-C]pyruvate oxidation. The results indicate that the effects of pentanoate are largely confined to the peroxisomal and the inner mitochondrial compartments whereas the effects of 4-pentenoic acid are confined to the peroxisomal and outer mitochondrial compartments.
Inherited organic acidemias are a group of metabolic disorders currently being described and investigated as gas-liquid chromatography is applied to unexplained diseases of infancy and childhood. Common clinical presentations include attacks of ketoacidosis, unexplained metabolic acidosis, failure of normal development, seizures, and other neurologic abnormalities. Hyperglycinemia, hyperammonemia, and hypoglycemia are other laboratory findings frequently present. Diagnosis depends on examination of urine, and sometimes blood, by gas-liquid chromatography to measure concentrations of organic acids and organic acid derivatives. Prognosis in many cases is excellent if diagnosis is made promptly and the metabolic acidosis can be reversed. Recovery from neurologic deficits has frequently been seen. Long-term therapy is generally dependent on restricting precursors of the toxic organic acid which builds up as a consequence of the enzyme deficiency. If there is some enzyme activity retained or if alternate metabolic pathways exist, success with therapy is likely.
Volatile free fatty acids (VFA) in blood increased approximately twofold in dogs subjected to total hepatectomy. The average total plasma VFA preoperatively was 1,585 mug percent and shortly before death, postoperatively, was 2,798 mug percent. The corresponding red cell concentrations were essentially the same. Acetic acid was 81 percent of the total VFA, propionic acid 7 percent, isobutyric acid 4 percent, butyric acid one percent, and isovaleric acid 5 percent. There was little or no isovalerate in red cells. The increments in the individual fatty acids after hepatectomy were highly variable, but the average increase with time was almost linear. The increase in VFA probably reflects an increased utilization of the branched-chain aminoacids by extrahepatic tissues.
We studied the effect of incubation temperature on the production of shortchain fatty acids (SCFA) by pig cecal bacteria in vitro in order to assess short-term influences of body temperature on bacterial metabolism in the large intestine. We employed a 200 mL scale continuous culture system using cecal bacteria from commercially slaughtered pigs as innoculum. The culture was maintained at 30, 37, 40 or 42 degrees C and continuously diluted by continuous feeding of bicarbonate buffer (pH 7.4) added with lactose (10 g/L) and by simultaneous continuous efflux both at 4.17 mL/h. We monitored SCFA concentration of the culture for 12 h, which represents their production rate. Concentrations of SCFA increased during the first several hours and plateaued at around 11 h of incubation. Incubation temperature significantly affected mean concentrations from 1 to 12 h of acetic (40 degrees C>42 degrees C= 37 degrees C>30 degrees C), propionic (40 degrees C>42 degrees C=30 degrees C), n-butyric (42 degrees C>37 degrees C>30 degrees C, 40 degrees C>30 degrees C) and n-valeric (42 degrees C=40 degrees C>37 degrees C>30 degrees C) acids, and total SCFA (40 degrees C>42 degrees C= 37 degrees C> 30 degrees C) (p<0.05). These results indicate that both hyperthermia and hypothermia depress the microbial breakdown of carbohydrates.
Anaerobic-aerobic batch experiments indicated that poly-hydroxy-alkanoate (PHA) form was important in determining the net phosphorus removal resulting from different volatile fatty acids (VFAs). Poly-3-hydroxy-butyrate (3HB) content was found to correlate fairly well with higher observed aerobic phosphorus uptake per unit PHA carbon degraded. Poly-3-hydroxy-valerate (3HV) correlated with lower aerobic phosphorus uptakes per unit PHA carbon degraded. These experiments, conducted with synthetic wastewater, imply that VFA speciation might have a significant effect on aerobic phosphorus uptakes and net phosphorus removal. In addition, the model parameter fP.UPT (Barker and Dold, 1997) could vary with the proportion of acetic to propionic acid received (i.e., the acetic/propionic acid ratio may be an important parameter for these systems). Carbohydrate data implied that the lower aerobic phosphorus uptake resulting from 3HV might have been caused by a greater fraction of PHA carbon shunting to carbohydrate biosynthesis during aerobiosis.
Environmental soil contamination at an industrial site in Marion, Ohio (USA) with tetrachloroethene (perchloroethene, PCE) resulted in residual cis-1, 2-dichloroethene (DCE) contamination that had not declined after more than 15 years. Microcosm slurries containing 2.6% soil from this site were supplemented with different electron donors, i.e., individual fatty acids or alcohols. None of the microcosms supported complete DCE dechlorination, unless PCE was added to the microcosm at initiation. The addition of fresh PCE resulted in the dehalogenation of PCE to DCE in the microcosms supplemented with fatty acids having an even number of carbon atoms (acetate, butyrate, and caproate), but not in those with an odd number of carbon atoms (formate, propionate, and valerate), where negligible or no activity was detected. No significant further DCE degradation was observed in any of the microcosms supplied with fatty acids as electron donors. Microcosms supplemented with freshly added PCE bioconverted PCE to DCE and completely dehalogenated both the ex-novo and soil-supplied DCE within 60 days, but only if alcohols having an even number of carbon atoms (ethanol or butanol) were also added as electron donors. Odd-numbered alcohols either did not produce dehalogenation (as with methanol) or only dehalogenated PCE to DCE (as with propanol).
A chemical, electrophysiological and behavioral study was carried out to analyze the volatile compounds of the Brindley's gland of Rhodnius prolixus Stål. Six compounds were found in the Brindley's gland of males and females: acetic, isobutyric, caproic acids and three compounds not identified. The mass spectra of the unidentified compounds have the appearance of a propionate ester, a butyrate ester and a valerate ester. There was no difference in the concentration of these compounds in the glands of males and females. The major component was isobutyric acid. The electroantennographic (EAG) evaluation of isobutyric, acetic, and caproic acids elicited weak responses. With both sexes, the EAG responses for the acids were no different from the control response at any of the doses evaluated (1, 10, 100, and 500 microg). The behavioral response of males and females to acetic, isobutyric, and caproic acids at 1, 5, and 10 microg and binary and tertiary mixtures of the three compounds was evaluated in a Y-olfactometer. Males showed preference for acetic acid at a dose of 1 microg, but not at 5 or 10 microg. Females showed preference for this compound at the dose of 5 microg. Males showed preference for isobutyric acid at 1 and 5 microg, but not at 10 microg. Females did not show any preference for isobutyric acid. Males were attracted to caproic acid at the dose of 1 and 10 microg. Females were attracted to the caproic acid. Males, but not females, preferred the mixture of acetic and isobutyric acids over control. Neither males nor females showed preference for the mixture of acetic and caproic acids or hexane control. Females, but not males, were attracted to the mixture of the isobutyric and caproic acids. Only males showed a positive response for the tertiary mixture of the acids.
N-Trifluoroacetyladriamycin-14-valerate differs from Adriamycin in its rapid intracellular transport and lack of fluorescent binding to nuclei or chromosomes. Both of these anthracyclines cause inhibition in the incorporation of labeled precursors into nucleic acids, extensive chromosomal damage, and arrest of cell cycle traverse in G2. In human lymphoid cells, N-trifluoroacetyladriamycin-14-valerate, unlike Adriamycin, does not show cell cycle phase-specific or proliferation-related cytotoxic effects. In an L1210 soft-agar assay, both Adriamycin and N-trifluoroacetyladriamycin-14-valerate show no enhanced sensitivity of mid-S-phase cells to their cytotoxic action.
Mitochondria of bovine liver contain acyl CoA synthetases necessary for the uptake of propionate, butyrate, and valerate whereas acetate is bound only weakly. Purification of these enzymes separated a distinct propionyl CoA synthetase highly specific for propionate and acrylate and a butyrate-activating fraction with broad substrate specificity for short and medium chain fatty acids. Evidence from kinetic studies and sucrose density centrifugation suggested that this latter fraction was composed of two enzymes, a butyryl CoA synthetase and a valeryl CoA synthetase. The apparent molecular weights of the propionyl, butyryl, and valeryl CoA synthetases were 72,000, 67,000, and 65,000. The Michaelis-Menten constants of propionyl CoA synthetase for propionate, adenosine 5'-triphosphate, and coenzyme A were 1.3 x 10(-3)M, 1.3 x 10(-3)M, and 6.3 x 10(-4)M. Enzyme activity is regulated by the concentration of propionate in portal blood. Relative to propionyl, butyryl, or valeryl CoA synthetases little acetyl CoA synthetase could be demonstrated. In ruminants hepatic metabolism is such that use of acetate as an energy source is minimum. This ensures that an alternative energy source to glucose, as acetate units, will reach the extrahepatic tissues. Separation of a distinct propionyl CoA synthetase regulated by the concentration of propionate in portal blood is significant because a primary role of ruminant liver is to synthesize glucose from ruminally derived propionate.
The pharmacokinetics of progesterone after oral administration were investigated. After a single dose of 100 mg, serum concentrations of progesterone around 50-60 nM and of 20 alpha-hydroxy-4-pregnene-3-one around 5-6 nM were recorded within 1-4 hours and elevated levels persisted for 8-12 hours. There were only minor changes in 17 alpha-hydroxyprogesterone concentrations and serum levels of androstenedione and cortisol were unaffected. A significant conversion of circulating progesterone into deoxy-corticosterone was demonstrated. During clinical treatment with oral progesterone the individual serum concentrations of this potent mineralocorticoid were closely correlated to the progesterone concentrations. This observation could be important as regards the etiology of certain clinical disorders characterized by fluid retention. According to competitive binding analyses there was no evidence that progesterone or medroxyprogesterone acetate could cause significant displacement of cortisol from corticosteroid-binding globulin during clinical treatment. The effects of natural and synthetic hormones upon subfractions of high density lipoprotein (HDL) cholesterol and liver proteins were followed in postmenopausal women during replacement therapy with various estrogen-progestogen combinations. The total serum cholesterol level was significantly reduced during treatment with all estrogen regimens. The concentrations of HDL cholesterol, HDL2 cholesterol, apolipoprotein A I and A II were increased in a dose-dependent pattern during unopposed estrogen therapy. The potency of 10 micrograms of ethinyl estradiol was estimated to be equivalent to 3-4 mg of estradiol valerate. Estrogen effects were significantly reversed by levonorgestrel 250 micrograms and also by medroxyprogesterone acetate 10 mg. During treatment with natural progesterone, no changes were recorded in HDL cholesterol or its subfractions. As compared with the lipoproteins, pregnancy zone protein and sex hormone binding globulin (SHBG) were found to be more sensitive to the alkylated than to the non-alkylated estrogen. Both levonorgestrel and medroxyprogesterone acetate clearly reduced SHBG levels after 3 months, whereas micronized progesterone had no such effect. While tamoxifen counteracted the therapeutic and metabolic effects of estrogen the sequential addition of estriol had no apparent influence. Unopposed estrogen treatment enhanced liver lecithin synthesis along pathway I, i.e. reduced the amount of stearic acid and increased the amount of palmitic acid. The effects were dose-dependent and no qualitative differences between ethinyl estradiol and estradiol valerate were recorded.
Sorbic acid concentrations as low as 0.1% produced transient erythema with edema and flare after open or closed application to human skin. Multiple areas of the body were tested. Reactions were most intense on the face but also could be produced on the back, forearm, and deltoid areas. Sorbic acid-induced erythema, edema, and flare were not associated with mast cell degranulation. Pretreatment of skin with topical steroids to induce vasoconstriction resulted in a diminished response to sorbic acid. Aspirin blocked the erythematous component, suggesting that prostaglandins are important mediators. Systemic steroids, antihistamines, and hydroxyzine failed to influence sorbic acid-induced erythema and edema. The anti-inflammatory effect of topical steroids was not affected by sorbic acid-induced erythema.
Concentrations of the two optic isomers of lactate (D- and L-form) as well as glucose, succinate, acetate, butyrate, isovalerate and valerate were examined in purulent sinus secretions. The samples were obtained from rabbit maxillary sinuses, experimentally infected with Streptococcus pneumoniae or Bacteroides fragilis. More soluble acids such as acetate displayed relatively low levels in the secretion, despite a high microbial production. A substantial increase in D-lactate concentration was found in secretions only the first day after induction of pneumococcal sinusitis, and not in bacteroides sinusitis. L-lactate levels were particularly high in secretions of a marked purulent character, and this isomer can be considered as indicator of anaerobic glycolysis in the leukocytes. Less diffusible fatty acids such as butyrate and isovalerate accumulated in the secretion, in spite of a relatively lower production rate, and are thus more reliable indicators of bacterial metabolism.
An incomplete anoxic fermentation of livestock waste results in offensive odor emissions. Antimicrobial additives may be useful in controlling odor emissions and pathogens. Natural antimicrobial compounds, carvacrol or thymol at 16.75 mM (2.5 g/l) completely inhibited the production of the offensive odor compounds, isobutyrate, valerate, isovalerate, and cresol, and significantly reduced other short-chain volatile fatty acids and gas emissions from swine waste. Fecal coliforms were reduced from 6.3 x 10(6) to 1.0 x 10(3) cells per ml 2 days after treatment with carvacrol (13.3 mM) and were not detectable within 14 days. Total culturable anaerobic bacteria were reduced from 12.4 x 10(10) to 7.2 x 10(8) cells per ml after 2 days and were suppressed below this level for 28 days. Lactate production was not prevalent in untreated swine waste indicating that the microbial populations differ from those in cattle waste. Carvacrol and thymol were stable in swine waste under anoxic conditions for 62 days with 90 to 95% of the additive being recovered in the waste solids. In conclusion, carvacrol and thymol are not metabolized in anoxic swine waste and they are potentially useful in controlling odor emissions and pathogens in swine waste.
Compounds known to be inhibitors of mixed-function oxidase systems inhibited the aerobic synthesis of hydroxylated carotenoids in Staphylococcus aureus U-71. Growth of the cells in the presence of 2-diethylaminoethyl-2,2-diphenyl valerate, 2,4-dichloro-6-phenylphenoxyethylamine, 2,4-dichloro-6-phenylphenoxyethyldiethylamine, and piperonyl butoxide reduced the levels of the rubixanthins found in stationary-phase cells by 75 to 97%. In cells grown with mevalonate-2-(14)C, the turnover rate of phytoene was reduced and the turnover rate of phytofluenol was increased in the presence of these inhibitors. The zeta- and delta-carotenes, which turn over in the absence of the inhibitors, accumulated (14)C in the presence of the inhibitors. This suggested that a mixed-function oxidase was responsible for the aerobic hydroxylation of delta-carotene in S. aureus U-71.
Mitochondria were prepared from kidney cortex tissue of lactating Holstein cows, and enzymes activating volatile fatty acids partially purified. Two fractions activating volatile fatty acids were obtained; one was similar to components isolated from bovine heart mitochondria activating acetate and propionate (acetyl CoA synthetase). The other was similar to components of bovine liver mitochondria and activated propionate, butyrate, and valerate but not acetate. On calcium phosphate gel chromatography this latter fraction could be separated into a distinct propionyl CoA synthetase (Michaelis-Menten constant for propionate 2.54 x 10(-3)M) and a fraction activating butyrate and valerate. The role of a distinct propionyl CoA synthetase in kidney mitochondria remains to be elucidated because propionate is not a major substrate in peripheral blood of ruminants. We concluded that volatile fatty acid activation by bovine kidney mitochondria is due to an acetyl CoA synthetase, a propionyl CoA synthetase, and a butyrate and valerate-activating fraction probably composed of separate butyryl and valeryl CoA synthetases.
Net absorption of L-lactate and VFA from the portal drained viscera of first lactation Holstein cows was measured at 4, 8, (four cows), 12, 16, and 20 wk (two cows) of lactation. Chronic indwelling catheters were installed 7 to 14 d postpartum in appropriate vessels to measure blood flow and net nutrient absorption. Cows were fed a completely mixed, 60:40 (dry basis) corn silage:supplement diet and milked every 12 h. Average metabolizable energy intake was 2.8X maintenance and mean milk production was 24.0 kg. Net absorption of lactate, any of the VFA, or their total was not affected by week postpartum. Net absorption of L-lactate, VFA, and alpha-amino N accounted in sum for 53.6% of metabolizable energy intake; contributions of each component to energy in absorbed nutrients were acetate and propionate, 29.5% each; alpha-amino N, 23.4%; L-lactate, 5.4%; n-butyrate, 5.3%; 2-methylbutyrate, 2.8%, and i-butyrate, i-valerate, and n-valerate, 1.2 to 1.6% each. Comparison of paired samples of blood and plasma showed that blood cells contribute to the transport of acetate, propionate, i-butyrate, and 2-methyl-butyrate but not of n-butyrate, i-valerate, or n-valerate.
Transaminase B (branched-chain amino acid aminotransferase, EC 2.6.1.42), the ilvE gene product, was purified to apparent homogeneity from an Escherichia coli K-12 strain which carries the ilvE gene both on the host chromosome and on a plasmid. The oligomeric structure of the enzyme, as determined by analytical ultracentrifugation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was confirmed to be that of a hexamer with a molecular weight of about 182,000 and apparently identical subunits. Cross-linking with dimethylsuberimidate yielded trimers, dimers, and monomers, but essentially no species of higher molecular weight. These results are consistent with a double-trimer arrangement of the subunits in native enzyme. The amino-terminal sequence was found to be: Gly Thr Lys Lys Ala Asp Tyr Ile (Trp) Phe Asn Gly (Thr) (Met) Val. Purified transaminase B catalyzed transamination between alpha-ketoglutarate and l-isoleucine, l-leucine, l-valine, and, to a lesser extent, l-phenylalanine and l-tyrosine, the latter reacting very sluggishly. The enzyme was free of aspartate transaminase and of transaminase C. The apparent K(m) values for the branched-chain alpha-ketoacids were smaller than those for the corresponding amino acids. The lowest K(m) was recorded for dl-alpha-keto-beta-methyl-n-valerate, and the highest was recorded for l-valine. The ratio of the valine- and isoleucine-alpha-ketoglutarate activities did not change significantly during purification, and both activities were quantitatively removed from crude extract by antibody raised against purified transaminase B. These observations argue against the existence of a separate valine-alpha-ketoglutarate transaminase. Anti-E. coli transaminase B antibody cross-reacted with crude extract from Salmonella typhimurium, but not with extract obtained from Pseudomonas aeruginosa.