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Propionic acidemia is a rare genetic disease associated with significant medical problems. When patients with this disease present for surgery, their anesthetic must be tailored to meet their special needs. This case report provides information regarding propionic acidemia and its anesthetic management.
A gram-negative, anaerobic, nonmotile, non-spore-forming, rod-shaped bacterium that fermented succinate quantitatively to propionate was isolated from a high dilution of rumen ingesta obtained from a dairy cow fed a production diet containing grass silage as the main roughage source. This organism did not grow on any of the following energy sources: 12 carbohydrates, pyruvate, lactate, 7 dicarboxylic acids, aspartate, citrate, and trans-aconitate. Both rumen fluid and yeast extract were necessary for good growth on succinate. The organism was negative for the following characteristics: production of propionate from threonine, protein digestion, sulfide production, nitrate reduction, catalase activity, and urease activity. There was no growth at 22 degrees C and reduced growth at 45 degrees C compared with growth at 39 degrees C. The DNA base composition was 52 mol% G + C. The complete 16S rRNA sequence (EMBL accession number, X81137) was obtained, and the phylogenetic relationships of the organism were determined. The most closely related genera were the genera Acidaminococcus and Phascolarctobacterium. The name proposed for this bacterium is Succiniclasticum ruminis gen. nov., sp. nov.; the type strain is strain SE10 (= DSM 9236). Additional isolation attempts revealed that S. ruminis is a common inhabitant of the rumina of cows that are fed production diets and of cows on pasture.
An anaerobic, thermophilic, syntrophic propionate-oxidizing bacterium, strain SI(T), isolated previously from granular sludge in a thermophilic upflow anaerobic sludge blanket (UASB) reactor, was characterized. The strain could grow fermentatively on pyruvate and fumarate in pure culture. The strain grew on propionate, ethanol, lactate, 1-butanol, 1-pentanol, 1,3-propanediol, 1-propanol and ethylene glycol in co-culture with the hydrogenotrophic methanogen Methanothermobacter thermautotrophicus strain deltaH(T). The optimum temperature for growth was 55 degrees C and the pH optimum was 7.0. The G+C content of the DNA was 52.8 mol %. Strain SI(T) contained MK-7 and MK-7(H4) as the major quinones and contained iso-C15:0 as the major fatty acid. Based on 16S rDNA sequence analysis, strain SI(T) formed a novel lineage within the gram-positive, spore-forming, sulphate-reducing bacterial group Desulfotomaculum. However, the strain lacked the ability to conduct dissimilatory sulphate reduction. Instead, it could reduce fumarate to succinate with concomitant growth on several organic substances as electron donor. These phenotypic and genetic properties support the formation of a novel species of a new genus, for which the name Pelotomaculum thermopropionicum gen. nov., sp. nov. is proposed. The type strain is strain SI(T) (= DSM 13744T = JCM 10971T).
Preliminary studies demonstrated that Clostridium sporogenes synthesized isoleucine by a pathway not involving threonine or threonine dehydratase. Radiotracer experiments with cells grown in a defined carbohydrate-free medium showed that radioactivity from [U-14C]serine, [3-14C]pyruvate, [14C]NaHCO3 and [1-], [2-] and [3-14C]propionate was incorporated into isoleucine. Conversely, there was no detectable incorporation of 14C into isoleucine during growth with [U-14C]glutamate, [U-14C]threonine, [U-14C]valine, [U-14C]leucine or [U-14C]methionine. Crude extracts of the bacteria grown in a minimal medium contained levels of alpha-acetohydroxyacid synthase activities comparable to those in Escherichia coli K12 grown in minimal medium. Stepwise degradation of isoleucine obtained from C. sporogenes grown in the presence of specifically-labelled precursors indicated that C. sporogenes can make isoleucine via the reductive carboxylation of propionate to yield alpha-oxobutyrate, which is metabolized to isoleucine in the classical fashion. Isoleucine was also formed by C. sporogenes via the reductive carboxylation of alpha-methylbutyrate to alpha-oxo-beta-methylvalerate.
A strictly anaerobic, propionate-producing bacterial strain (WB4T) isolated from rice plant residue in anoxic rice-field soil in Japan was characterized phenotypically and phylogenetically. Cells were Gram-negative, non-motile, non-spore-forming, short rods. The strain utilized various sugars and produced propionate and acetate as major fermentation products with a small amount of succinate. The optimum growth temperature was 30 degrees C. Oxidase, catalase and nitrate-reducing activities were negative. The major cellular fatty acids were anteiso-C(15 : 0), C(15 : 0) and anteiso-C(17 : 0) 3-OH. Menaquinone MK-8(H4) was the major respiratory quinone. The genomic DNA G+C content was 39.3 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence placed the strain in the phylum 'Bacteroidetes'. The closest relative to strain WB4T was an environmental clone from water contaminated with equine manure (sequence similarity of 99.7 %) and the strain formed a distinct cluster with other environmental clones mainly from freshwater sediments. The closest recognized species were members of the genus Dysgonomonas, with 16S rRNA gene sequence similarities of 90.9-89.8 %. Bacteroides merdae was the next closest recognized species (similarity of 88.7 % to the type strain). Given that the ecological, physiological and chemotaxonomic characteristics of strain WB4T were different from those of any related species, a new genus and species Paludibacter propionicigenes gen. nov., sp. nov., is proposed to accommodate it. The type strain is WB4T (= JCM 13257T = DSM 17365T).
The clinical and neuropathological findings are described in two children with propionic acidaemia presenting in infancy; they survived for 4 and 16 years respectively. Abnormalities were noted in the basal ganglia of both patients. In one child who clinically had severe athetosis, there was marbling of the corpus striatum. Clinical and morphological evidence suggests that the basal ganglia are especially vulnerable in propionic acidaemia.
Incorporation of radiolabel from propionate-1(-14)C into protein (TCA insoluble material) in fibroblasts or amniotic fluid cells, provides a rapid, simple means of detecting fetuses with inborn errors of propionate metabolism using small numbers of cells. Controls were easily differentiated from mutant lines over differing media pH conditions. This method was successfully used to diagnose correctly a normal fetus at risk for methylmalonic acidemia. This method can be used as an adjunct in diagnosis, but cannot replace direct enzyme analysis.
Prenatal diagnosis of propionic acidemia can be performed by two independent methods: measuring an elevated quantity of the metabolite methylcitrate in amniotic fluid; and demonstrating deficient activity of propionyl-CoA carboxylase in amniocytes cultured from the fluid. Discordant results in a pregnancy at risk for propionic acidemia were obtained. Elevated concentration of methylcitrate indicated an affected fetus, but the activity of propionyl-CoA carboxylase was normal. An affected female infant was born. Chromosome variant analysis demonstrated that between passage two and four overgrowth of the female fetal cells by contaminating maternal cells led to the "false negative" results obtained by enzyme assay. This experience demonstrates the value of analysis of abnormal metabolites in amniotic fluid and highlights a problem that could confound the prenatal diagnosis of any condition assessed by enzyme activity.
The present study deals with the usefulness of 1H-NMR spectroscopy in the chemical diagnosis of propionic acidemia and methylmalonic acidemia. A Varian VXR-500 spectrometer was used. 1H-NMR spectra of urine from a patient with propionic acidemia show peaks of 3-hydroxy-n-valerate, methylcitrate, propionyl glycine, 3-hydroxy-n-butyrate, lactate, 3-hydroxypropionate, tiglylglycine and hippurate. The assignment was made possible by the use of 2D COSY. The spectra from a patient with methylmalonic acidemia show methylmalonate and glycine. 1H-NMR spectroscopy has the advantages of requiring a short time for analysis, relatively small amounts of urine and no preliminary extraction.
Fermentation balances and growth yields were determined with various bacteria fermenting lactate to acetate plus propionate either via methylmalonyl-CoA or via acrylyl-CoA. All strains fermented lactate to acetate plus propionate at approximately a 1:2 ratio. Growth yields of Propionibacterium freudenreichii were more than twice as high as those of Clostridium homopropionicum or Veillonella parvula. Hydrogen was formed as a side product to a significant extent only by V. parvula and Pelobacter propionicus; the latter formed hydrogen preferentially when using ethanol as substrate. Acrylyl-CoA reductase of C. homopropionicum and Clostridium neopropionicum was found nearly exclusively in the cytoplasm thus confirming that this reduction step is unlikely to be involved in energy conservation. C. homopropionicum exhibited higher K(S) and higher micro(max) values, as well as higher specific substrate turnover rates than P. freudenreichii. The results allow us to conclude that C. homopropionicum using the acrylyl-CoA pathway with low growth yield obtains its specific competitive advantage compared to P. freudenreichii not through higher substrate affinity or metabolic shift toward enhanced acetate-plus-hydrogen formation but through faster specific substrate turnover.
Itaconate is known as a potent inhibitor of isocitrate lyase. Unexpectedly, itaconate was a strong inhibitor of acetate and propionate assimilation in isocitrate lyase-negative purple non-sulfur bacterium Rhodospirillum rubrum. It was shown that in cell extracts of R. rubrum itaconate inhibited propionyl-CoA carboxylase (PCC) activity. The participation of PCC in propionate assimilation in R. rubrum is well-documented, but the inhibition of acetate assimilation suggests that PCC is also involved in acetate metabolism. PCC is one of the enzymes of the citramalate cycle, the anaplerotic pathway proposed for R. rubrum as a substitute for the glyoxylate cycle. These results provide further support for the hypothesis of the occurrence of the citramalate cycle in R. rubrum. PCC from other isocitrate lyase-negative phototrophs, Rhodobacter sphaeroides and Phaeospirillum fulvum, was not inhibited by itaconate.
The structural and functional barrier preventing the free advancement of microbial plaque subgingivally along the tooth surface is formed by the junctional epithelial (JE) cells directly attached to the tooth (DAT cells). The mechanism leading to degeneration of the DAT cells is not known. In the present study we examined the possible role of short chain fatty acids (SCFAs) on epithelial cells by making use of 2 epithelial cell cultures (HaCaT and ERM) and an explant culture model of human JE. The SCFAs butyrate and propionate were used in concentrations found in human plaque and gingival crevicular fluid (0.25-16.0 mM). The SCFAs had no effect on primary cell adhesion nor on the epithelial attachment apparatus (EAA). By contrast, even 0.25 mM of butyrate significantly retarded epithelial cell growth. Similar effects with propionate were first observed at concentrations higher than 1.0 mM. The retardation of epithelial cell growth was found to be due to inhibition of cell division. Furthermore, after butyrate treatment dense accumulations of intermediate filaments and cytoplasmic vacuolization were characteristically seen in cells adjacent to cells of normal appearance. This suggests that some cells of the growing epithelial cell population are more sensitive to the SCFAs than others, and agrees with previous reports on the DAT cells of periodontally-involved teeth in vivo. The results suggest that SCFAs are microbial factors that play a role in the initiation and progression of periodontal pocket formation by impairing epithelial cell function rather than having a direct effect on the EAA.
Propionate and pyruvate added to isolated normal and biotin-deficient adult rat hepatocytes increase the production of glucose. This production decreases about 30% on biotin deficiency. Malonate inhibits gluconeogenesis from propionate showing the metabolic transformation of propionyl-CoA via the Krebs cycle. Neither glucagon nor dibutyryl-cyclic AMP significantly stimulate gluconeogenesis.
1. The interaction of beta-guanidino propionic acid and gamma-aminobutyric acid has been investigated on the crayfish muscle by measurement of the membrane conductance.2. The increase in membrane conductance produced by GABA is depressed by beta-guanidino propionic acid. This antagonist acts in a competitive way as shown by the shift of log dose-response curves and by the results of tests for competitive interaction (method of Schild (1947); Lineweaver and Burk's plot).3. Perfusion of GABA was shown to induce a receptor desensitization. As a consequence, the slope of the dose-response curve plotted in Hill's co-ordinates increases when care is taken to minimize this phenomenon. The significance of this slope for establishing the real number of GABA molecules binding with the GABA receptor is discussed.
Comparison of the kinetics of the inward Ca(2+) ion flux to (S)-alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid [(S)-AMPA] in cerebrocortical homogenates and that of the previously reported transmembrane Na(+) ion influx mediated by an AMPA receptor in hippocampal homogenates established that the agonist-induced opening of the AMPA receptor channels occurs in two kinetically distinguishable phases. Here we report that the 2-methyl-4-oxo-3H-quinazoline-3-acetic acid (Q1) inhibits the major slow-phase response specifically, whereas the acetyl piperidine derivative (Q5) is a more potent inhibitor of the fast-phase response. Both the quinazolone-3-propionic acid (Q2) and the quinazolone-3-acetic acid methyl ester (Q3) enhanced the slow-phase response to (S)-AMPA. The information provided by docking different Q1, Q2, and Q5 models at the ligand-binding core of iGluRs were used to define agonistic and antagonistic modes of interactions. Based on the effects of quinazolone-3-alkyl-carboxylic acid derivatives on specific [(3)H]Glu binding and kinetically distinguishable Ca(2+) ion permeability responses to (S)-AMPA and molecular modeling, the fast- and the slow-phase (S)-AMPA-elicited Ca(2+) ion fluxes were corresponded to different subunit compositions and degrees of S1S2 bridging interaction relative to substitution of kainate thereupon. Substitutions of agonists and antagonists into the iGluR2 S1S2 ligand binding core induced different modes of domain-domain bridging.
A novel method for measuring the kinetics of a subgroup of organisms growing in mixed culture was used to measure the kinetics of propionate-using organisms in a mixed-population anaerobic digester. It was shown that there are at least two subgroups of propionate-using organisms with distinctly different growth kinetics. Both subgroups could grow without reducing sulfate. The slower-growing subgroup had a Ks of 11 mg/liter and a mumax of 0.0054 h-1 which is similar to the mumax reported for Syntrophobacter wolinii. The faster-growing group had a mumax of 0.050 h-1 and a Ks of 330 mg/liter. The slower-growing group was inhibited by a pH shock from 7.0 to 6.0, whereas the faster-growing group was less sensitive to the pH shock.
Potassium sorbate and sodium propionate brought about a marked inhibition in the growth of Penicillium expansum and a proportionally greater inhibition in the synthesis of patulin by the mold. At inhibitor concentrations used commercially in bakery products, propionate inhibited growth less efficiently than sorbate did but was a more effective inhibitor of patulin synthesis.
The pathways of short-chain fatty acid (SCFA; acetate, propionate, and butyrate) formation from glucose were determined for the human fecal microbial communities of two subjects. The pathways were identified by radioisotope analysis of the SCFA and CO2 obtained after incubation of fecal suspensions with glucose under 20% CO2 with [1-14C]glucose, [3,4-14C]glucose, or 14CO2. Acetate was chemically degraded to learn the labeling of the methyl and carboxyl carbons. The labeling of CO2 and acetate showed that the major route of glucose catabolism was the Embden-Meyerhof-Parnas pathway, with production of CO2 from pyruvate carboxyl carbon. Labeling of the methyl and carboxyl carbons of acetate by 14CO2 or [3,4-14C]glucose proved that acetate was formed from CO2 by the Wood-Ljungdahl pathway. CO2 reduction accounted for about one-third of the acetate formed by suspensions from subject 1 and about one-fourth of the acetate formed by suspensions from subject 2. Propionate was formed by a CO2 fixation pathway, and butyrate was formed by classical routes of acetyl-S coenzyme A condensation. The amount of CO2 formed from [1-14C] glucose and acetate labeling patterns obtained with the other 14C precursors indicated that the Entner-Doudoroff, transketolase-transaldolase, and heterolactic pathways were not significant. Fermentation of cabbage cellulose by subject 1 followed the same pathways as were used for glucose. The results with suspensions from subject 2 suggested that some radioactive acetate was formed from the C-3 of glucose by the Bifidobacterium pathway.