Excretion Of Organic Acids Research Articles

Zinc Phosphate and Pyromorphite Solubilization by Soil Plant-Symbiotic Fungi

Acidolysis, complexolysis and metal accumulation were involved in solubilization of zinc phosphate and pyromorphite by a selection of soil fungi representing ericoid and ectomycorrhizal plant symbionts and an endophytic/entomopathogenic fungus, Beauveria caledonica. Zinc phosphate was much more readily solubilized than pyromorphite. According to the relationship between metal mobilization and pH, acidolysis (protonation) was found to be the major mechanism of both zinc phosphate and pyromorphite dissolution for most of the fungi examined. In general, the more metal tolerant fungal strains yielded more biomass, acidified the medium more and dissolved more of the metal mineral than less tolerant strains. However, B. caledonica 4 excreted a substantial amount of oxalic acid (∼ 0.8 mM) in the presence of pyromorphite that coincided with a dramatic increase in lead mobilization providing a clear example of complexolysis. Organic acid excretion by fungi was inter- and intraspecific and was strongly influenced by the presence of the toxic metal minerals. When grown on zinc phosphate or pyromorphite, Hymenoscyphus ericae DGC3(UZ) accumulated the lowest metal concentration, but Thelephora terrestris accumulated the highest metal concentration in the biomass. The ability to accumulate water-soluble lead species, representing mainly cytosolic and vacuolar pools, seemed to be connected with pyromorphite-solubilizing ability. B. caledonica 4, which demonstrated the highest ability to dissolve pyromorphite, accumulated the highest water-soluble fraction and total lead concentration in the mycelium. Generally, isolates with a higher zinc-tolerance accumulated significantly less total zinc from zinc phosphate (including the sum of water-soluble and NaCl-extractable zinc) than non-tolerant strains.

The Response of Lupinus albus Roots to the Signal from Phosphorus-Deficient Substrate1

The excretion of organic acids into the rhizosphere is induced by low phosphorus content in roots of white lupine (Lupinus albus L.). The aim of this study was to investigate how did the white lupine roots respond to the signals of P-deficiency in the substrate, by using the method of separating the root system into two parts, one part being placed into P-deficient solution and another part into P-sufficient solution. The results showed that the root tips (1-cm-long) accept the signal of P-deficiency in the substrate. This signal can be transmitted from one root tip to another, and can induce the accumulation and excretion of malic acid in the root tips and the development of proteoid roots. In order to investigate whether a phytohormone was involved in the response, the external hormones were used. Indole-3-butyric acid added to P-sufficient solution can induce the development of proteoid roots, but without any accumulation of citric acid in them. On the contrary, 6-benzyladenine (BA) added to the P-deficient solution can inhibit the development of proteoid roots and the accumulation of malic acid in the root tips. The inhibitory effect increases with increasing BA supply.

Intracellular pH of Streptomyces pristinaespiralis is correlated to the sequential use of carbon sources during the pristinamycins-producing process

This work assesses, with epifluorescence microscopy and an image analysis method, glucose and amino acid metabolisms as carbon sources during pristinamycin batch production process in correlation with intracellular pH-variations. At the start of the culture, results suggested preferential consumption of glutamate as carbon source over glucose and arginine. Besides, sequential use of glutamate and arginine as nitrogen sources has been observed, glutamate being assimilated before arginine. Once the glutamate is exhausted, glucose and arginine begin to become metabolised. Shortly before pristinamycin excretion, a massive lactate and succinate excretion occurs. Excretion of pristinamycins and organic acids and glucose and amino-acid consumption were shown to be correlated to measured intracellular pH-fluctuations, so that many cytoplasmic pH-variations can be explained by this study.

Alteration of citrate metabolism in cluster roots of white lupin.

Organic acid excretion plays a key role in the superior P(i)-acquisition of barely soluble inorganic P sources from soils. Seedlings of white lupin (Lupinus albus L.) grown for 37 d in -P nutrient solution showed typical -P symptoms, such as low P content, increased root/shoot ratio and the development of cluster roots which released large amounts of citrate. Citrate concentration in the cluster roots was 21.5 micro mol (g FW)(-1), which corresponded to a 4.3- and 2.6-fold increase of +P and -P root apexes, respectively. Cluster roots possessed higher phosphoenolpyruvate carboxylase and phosphoenolpyruvate phosphatase activity than those in +P root apexes, which could result in increasing the supply of substrate for citrate synthase. On the other hand, the cytosolic pathway which converts citrate to 2-oxoglutarate consists of aconitase and NADP-specific isocitrate dehydrogenase activity that was lower in the cluster roots than in +P root apexes, and may contribute to citrate accumulation. Thus, metabolic balance with these alterations would play an important role in increasing citrate concentration in the cluster roots. The molecular characterization of NADP-specific isocitrate dehydrogenase indicated that the cytosolic isoenzyme functions as a hetero-dimer, and that the activity would be regulated by the transcript levels for both isoforms.

Acidose métabolique et insuffisance rénale en réanimation

The kidney plays an essential role in acid-base regulation by reabsorbing the filtered bicarbonate and excreting a net acid load by titrating the phosphate and ammonia buffers present in the urine. Metabolic acidosis is defined by the accumulation of non-volatile acids, resulting from a deficit in urinary acidification, an increased acid generation or acid load, or a digestive or renal bicarbonate loss. The anion gap, which reflects the amount of unmeasured anions in the serum, is increased in anion gap metabolic acidosis but remains normal in hyperchloremic metabolic acidosis. The renal causes of hyperchloremic metabolic acidosis include proximal (type 2), distal (type 1), and hyperkalemic (type 4) renal tubular acidoses, as well as moderate renal failure. Advanced renal failure is associated with a marked decrease in the excretion of organic acids, thereby leading to anion gap metabolic acidosis. Treatment of metabolic acidosis primarily depends on its cause. The administration of sodium bicarbonate is reserved to severe metabolic acidosis (blood pH < 7,20). This treatment may induce extracellular-fluid volume overload and is associated with an increase in the CO 2 partial pressure in tissues.

Effects of probiotics, lactitol and rifaximin on intestinal flora and fecal excretion of organic acids in cirrhotic patients

AIM: The aim of the present study was to assess fecal organic acid excretion and gut flora changes in a group of patients with compensated liver cirrhosis without hepatic encephalopathy by comparing pro­biotic therapy with more common therapeutic approaches.METHODS: Thirty patients with compensated Child B liver cirrhosis were allocated into one of three matched groups, which were randomly given one of three 3‐week oral treatments: (i) lactitol 20 g t.i.d.; (ii) 400 mg rifaximin b.i.d.; or (iii) the synbiotic SCM‐III (Microflorana‐F, Named, Lesmo, Italy) 10 mL t.i.d. Stool samples were collected at both the time of entry into the study and at the end of the trial period for the assessment of intestinal bacterial flora and for the determination of fecal pH and of organic acid concentration.RESULTS: All three tested compounds significantly increased the total anaerobic bacterial count to the same extent. The change was mainly due to a reduction in the Bacteriodes population and an expansion of the bifidobacteria population. However, only SCM‐III significantly decreased the total count of Bacteroides and Clostridium. Lactitol and SCM‐III decreased (to a similar extent) the fecal pH compared with healthy controls and with pretreatment values (P &lt; 0.05). Both lactitol and SCM‐III produced a significant increase in the fecal concentration of acetic acid and lactic acid. However, only SCM‐III decreased the fecal concentration of toxic short‐chain fatty acids.CONCLUSIONS: In the present clinical study, we confirmed the findings from an in vitro study of enhanced‐non‐toxic organic acid recovery from stools during treatment with nonabsorbable disaccharides. In the present study, we found that lactitol did not produce any significant effect on Bacteroides and Clostridium, whereas the specific bacterial counts of such species significantly decreased only in the group treated with the synbiotic. These data suggest a potential role of synbiotics in the long term treatment of chronic liver disease.

ATP citrate lyase: cloning, heterologous expression and possible implication in root organic acid metabolism and excretion

AbstractIn order to cope with phosphate deficiency, white lupin produces bottle‐brushed like roots, so‐called cluster or proteoid roots which are specialized in malate and citrate excretion. Young, developing cluster roots mainly excrete malate whereas mature cluster roots mainly release citrate. Mature proteoid roots excrete four to six times more carboxylates compared with juvenile proteoid roots. Using a cDNA‐amplified restriction fragment length polymorphism (AFLP) approach we identified a gene coding for a putative ATP‐citrate lyase (ACL) up‐regulated in young cluster roots. Cloning of the lupin ACL revealed that plant ACL is constituted by two polypeptides (ACLA and ACLB) encoded by two different genes. This contrasts with the animal ACL, constituted of one polypeptide which covers ACLA and ACLB. The ACL function of the two lupin gene products has been demonstrated by heterologous expression in yeast. Both subunits are required for ACL activity. In lupin cluster roots, our results suggest that ACL activity could be responsible for the switch between malate and citrate excretion in the different developmental stages of cluster roots. In primary roots of lupin and maize, ACL activity was positively correlated with malate exudation. These results show that ACL is implicated in root exudation of organic acids and hence plays a novel role in addition to lipid synthesis. Our results suggest that in addition to lipid biosynthesis, in plants, ACL is implicated in malate excretion.

Gas chromatography–mass spectrometry profile of urinary organic acids of Wistar rats orally treated with ozonized unsaturated triglycerides and ozonized sunflower oil

The main products in the ozonolysis of unsaturated triglycerides or vegetable oils are peroxides, aldehydes, Criegee ozonides and carboxylic acids. Some of these compounds are present in different concentrations in the biological fluids. The aim of this work is to study, using gas chromatography–mass spectrometry (GC–MS), the organic acid excretion in urine of rats orally treated with ozonized sunflower oil (OSO), ozonized triolein or ozonized trilinolein. Oral administration of OSO to Wistar rats has produced changes in the urinary content of dicarboxylic organic acids. Among others heptanedioic (pimelic acid) and nonanedioic acids (azelaic acid) were the major increased dicarboxylic acids found. The urinary dicarboxylic acid profiles of rats which received ozonized triolein only showed an increase in heptanedioic and nonanedioic acids. However, when ozonized trilinolein is applied, the profile is similar to that obtained when OSO is administered. A biochemical mechanism is proposed to explain the formation of dicarboxylic acids from ozonated unsaturated triglycerides.

AniA regulates reserve polymer accumulation and global protein expression in Rhizobium etli.

Previously, it was reported that the oxidative capacity and ability to grow on carbon sources such as pyruvate and glucose were severely diminished in the Rhizobium etli phaC::OmegaSm(r)/Sp(r) mutant CAR1, which is unable to synthesize poly-beta-hydroxybutyric acid (PHB) (M. A. Cevallos, S. Encarnación, A. Leija, Y. Mora, and J. Mora, J. Bacteriol. 178:1646-1654, 1996). By random Tn5 mutagenesis of the phaC strain, we isolated the mutants VEM57 and VEM58, both of which contained single Tn5 insertions and had recovered the ability to grow on pyruvate or glucose. Nucleotide sequencing of the region surrounding the Tn5 insertions showed that they had interrupted an open reading frame designated aniA based on its high deduced amino acid sequence identity to the aniA gene product of Sinorhizobium meliloti. R. etli aniA was located adjacent to and divergently transcribed from genes encoding the PHB biosynthetic enzymes beta-ketothiolase (PhaA) and acetoacetyl coenzyme A reductase (PhaB). An aniA::Tn5 mutant (VEM5854) was constructed and found to synthesize only 40% of the wild type level of PHB. Both VEM58 and VEM5854 produced significantly more extracellular polysaccharide than the wild type. Organic acid excretion and levels of intracellular reduced nucleotides were lowered to wild-type levels in VEM58 and VEM5854, in contrast to those of strain CAR1, which were significantly elevated. Proteome analysis of VEM58 showed a drastic alteration of protein expression, including the absence of a protein identified as PhaB. We propose that the aniA gene product plays an important role in directing carbon flow in R. etli.

Metabolic changes associated with cluster root development in white lupin (Lupinus albus L.): relationship between organic acid excretion, sucrose metabolism and energy status.

Under phosphorous deficiency, plants of white lupin (Lupinus albus L.) develop root clusters, which are also called proteoid roots due to their preferential presence in the Proteaceae. In their mature stage, these roots acidify the soil and excrete high amounts of carboxylates [up to 1.5 and 7 micromol (g FW)(-1) h(-1) of malate and citrate, respectively] enabling lupins to utilise sparingly available sources of phosphate. Using the amplified fragment length polymorphism (AFLP) technique, we identified genes predominantly expressed in juvenile and mature cluster roots. Transcripts for two enzymes involved in glycolysis, fructokinase and phosphoglucomutase, were identified in juvenile cluster roots and one, sucrose synthase, in mature cluster roots. In order to verify these observations we performed quantitative reverse transcription-polymerase chain reaction (RT-PCR) and could confirm the increased transcript level. Measurements of enzymatic activities showed that fructokinase and phosphoglucomutase activities increased in juvenile cluster roots, whereas sucrose synthase activity was maximal in mature cluster roots. These results indicate that formation of proteoid roots and citrate excretion increase sink strength locally. Production of citrate and inhibition of respiration are likely to result in an increased NADH/NAD+ ratio, which may be toxic for the plant. The fermentation pathway would allow oxidation of NADH by decarboxylation of pyruvate and subsequent reduction of the resulting acetaldehyde. Determination of alcohol dehydrogenase activity showed that this enzyme is strongly induced in mature proteoid roots. However, ethanol production was not increased, indicating that pyruvate is shunted to citrate synthesis and not to ethanol production.

Excess cation uptake, and extrusion of protons and organic acid anions by Lupinus albus under phosphorus deficiency

In symbiotically-grown legumes, rhizosphere acidification may be caused by a high cation/anion uptake ratio and the excretion of organic acids, the relative importance of the two processes depending on the phosphorus nutritional status of the plants. The present study examined the effect of P deficiency on extrusions of H + and organic acid anions (OA −) in relation to uptake of excess cations in N 2-fixing white lupin (cv. Kiev Mutant). Plants were grown for 49 days in nutrient solutions treated with 1, 5 or 25 mmol P m −3 Na 2HPO 4 in a phytotron room. The increased formation of cluster roots occurred prior to a decrease in plant growth in response to P deficiency. The number of cluster roots was negatively correlated with tissue P concentrations below 2.0 g kg −1 in shoots and 3 g kg −1 in roots. Cluster roots generally had higher concentrations of Mg, Ca, N, Cu, Fe, and Mn but lower concentrations of K than non-cluster roots. Extrusion of protons and OA − (90% citrate and 10% malate) from roots was highly dependent on P supply. The amounts of H + extruded per unit root biomass decreased with time during the experiment. On the equimolar basis, H + extrusion by P-deficient plants (grown at 1 and 5 mmol P m −3) were, on average, 2–3-fold greater than OA − exudation. The excess cation content in plants was generally the highest at 1 mmol P m −3 and decreased with increasing P supply. The ratio of H + release to excess cation uptake increased with decreasing P supply. The results suggest that increased exudation of OA − due to P deficiency is associated with H + extrusion but contributes only a part of total acidification.

Origins of Spurious Organic Acidurias

The diagnosis of inborn errors of organic acid metabolism is based on the assumption that the sudden appearance or elevation of diagnostic, urinary organic acids is directly related to a specific enzymatic defect. The assumption may be misleading because there are instances in which other mechanisms may be responsible. In the rush to get laboratory results out, these factors may not be given sufficient consideration. Age and Dietary Considerations The neonate, because of the immaturity of its physiologic systems, will often show compounds in the urine different from those of older children. Chalmers and Lawson 1(pp 189-190) noted that the effects of diet on organic acid excretion patterns are much greater in newborns than in older children and adults. High levels of 2-oxoglutaric acid are often seen, and elevated levels of fumaric acid are occasionally seen. Both could be partially caused by alterations in the Krebs cycle and acid-base metabolism. Adipic acid is a 6-carbon, medium-chain dicarboxylic acid seen in small amounts in the urine of newborns. The presence of large amounts of the compound is usually indicative of an error of metabolism. Glick and Fischer 2 reported large amounts of adipic acid in urine of children eating gelatins. In that report and in 2 of the 3 cases we observed, adipic acid was the only diagnostic organic acid level elevated. Our third case, a patient with isovaleric aciduria recovering from an episodic attack, showed a sudden appearance of a large amount of adipic acid along with a high level of isovalerylglycine. The adipic acid was traced to Pregestimil (Mead Johnson), a milk formula fortified with medium-chain triglycerides (MCT) in which 75% of the fatty acids originate with a 6-carbon dicarboxyilc acid. In addition to adipic acid, other medium-chain dicarboxylic acids are commonly found in the course of urinary organic acid screening. Usually, these occurrences are not due to inborn errors of metabolism. Dicarboxylic aciduria may be secondary to fasting, diabetic ketoacidosis, anticonvulsant therapy, an MCT-containing diet, and neonatal enzymatic immaturity. 3

Pharmacokinetics and Renal Excretion of Diphenhydramine and its Metabolites, Diphenylmethoxyacetic Acid and Diphenhydramine‐N‐Oxide, in Developing Lambs

The developmental disposition of diphenhydramine (DPHM) and its metabolites, diphenylmethoxyacetic acid (DPMA) and DPHM‐N‐oxide (DPHMNO), was investigated in postnatal lambs. Lambs received a DPHM intravenous (iv) bolus 15 days (Group A; n = 5) or 2 months (Group B; n = 6) after birth. Total body clearance of DPHM in postnatal lambs (Group A = 138.7 ± 80.5 mL/min/kg; Group B = 165.7 ± 51.3 mL/min/kg) was similar to the nonplacental clearance values (i.e., the component of fetal total body clearance that is not due to elimination via the placenta) estimated for fetal lamb (116.3 ± 49.6 mL/min/kg), and significantly greater than estimates in adult sheep (38.5 ± 12.3 mL/min/kg). In addition, Group A DPHM renal clearance (CLr, >1.80 ± 1.24 mL/min/kg) was similar to that of the fetus (2.06 ± 0.24 mL/min/kg), and significantly greater than that for Group B (0.26 ± 0.17 mL/min/kg) and the adult (0.012 ± 0.005 mL/min/kg). In contrast, similar to the fetal situation, postnatal DPMA CLr (Group A = 0.02 ± 0.02 mL/min/kg; Group B = 0.05 ± 0.01 mL/min/kg) was significantly less than adult values (0.53 ± 0.19 mL/min/kg). Because DPMA is not sequentially metabolized in sheep, the lower CLr in postnatal lambs results in longer apparent elimination half‐lives of this metabolite (Group A = 90.4 ± 32.2 h; Group B = 13.13 ± 11.0 h) compared with that in the adult (2.9 ± 1.6 h). No age‐related difference in DPHMNO CLR was observed. Alterations in the CLr of DPHM and DPMA are likely related to differences in the rate of development of mechanisms (i.e., tubular secretion and reabsorption and glomerular filtration rate) involved in the urinary drug excretion of organic acids and bases. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1362–1370, 2000

Weathering of rocks and neogenesis of minerals associated with lichen activity

The weathering action of lichens on rocks and the biogeophysical and biogeochemical alteration of rock-forming minerals, their influence in dissolution and precipitation reactions and in bioformation of new minerals are reviewed. The intimate adhesion of lichen thalli to the rock surface and the hyphal penetration in less coherent areas of the rock cause a physical disaggregation and fragmentation of the mineral surface. Chemical weathering is essentially due to the excretion of organic acids. Depending on the nature of the minerals, etching patterns and decomposition features are formed by biosolubilisation processes. The presence of calcium, magnesium, manganese and copper oxalate crystals at the rock–lichen interface and in the lichen thalli suggests that oxalic acid, secreted by the mycobiont, is one of the most active agents of chemical alteration. Transformation of minerals to siliceous relicts, precipitation of iron oxides and hydroxides and formation of alumino-silicates are presumably related to the activity of organic acids in complexing and removing elements from the substrate. The involvement of the so-called `lichen acids', a group of mainly polyphenolic compounds, as bioweathering agents has been only recently well documented. Present and further progresses in the study of the lichen–rock relationship rely on application of modern instrumental and analytical techniques. The relevance of lichen weathering to the biodeterioration of stoneworks of artistic value is considered.

Evaluation of Urinary Acylglycines by Electrospray Tandem Mass Spectrometry in Mitochondrial Energy Metabolism Defects and Organic Acidurias

We analyzed the urinary acylglycine excretion in 26 patients with mitochondrial energy metabolism disorders and in 55 patients with organic acidurias by electrospray tandem mass spectrometry (ESI-MS/MS), monitoring precursor ions of m/z 90. Urinary concentrations of the different acylglycines were quantified using deuterated internal standards. Normal values for the most important acylglycines were established. In MCAD and MAD (neonatal form) deficiencies, typical excretion patterns of urinary acylglycines were found in all the samples. In isovaleric aciduria, propionic aciduria, and 3-methylcrotonylglycinuria typical glycine conjugates were always found. Methylmalonic aciduria (mutase deficiency), multiple carboxylase deficiency, and 3-hydroxy-3-methylglutaric aciduria revealed pathological acylglycine profiles, even if not specific for the disease. In all these diseases acylglycine excretion seems to be less influenced by the clinical status than organic acid excretion. This method is a useful diagnostic tool for these metabolic disorders, complementary to organic acids and acylcarnitine profiles.

Weathering of rocks induced by lichen colonization — a review

The evidence presented by numerous investigations of the interface between lichens and their rock substrates strongly suggests that the weathering of minerals can be accelerated by the growth of at least some lichen species. The effects of lichens on their mineral substrates can be attributed to both physical and chemical processes. The physical effects are reflected by the mechanical disruption of rocks caused by hyphal penetration, expansion and contraction of lichen thallus, swelling action of the organic and inorganic salts originating from lichen activity. Lichens also have significant impact in the chemical weathering of rocks by the excretion of various organic acids, particularly oxalic acid, which can effectively dissolve minerals and chelate metallic cations. As a result of the weathering induced by lichens, many rock-forming minerals exhibit extensive surface corrosion. The precipitation of poorly ordered iron oxides and amorphous alumino-silica gels, the neoformation of crystalline metal oxalates and secondary clay minerals have been frequently identified in a variety of rocks colonized by lichens in nature. For a better understanding of the impacts of lichens on environments, further work on the comprehensive involvement of the lichen effects on weathering of natural rocks, deterioration of building stones and stonework, and formation of primitive soils should be carried out.

Role of CcpA in regulation of the central pathways of carbon catabolism in Bacillus subtilis.

The Bacillus subtilis two-dimensional (2D) protein index contains almost all glycolytic and tricarboxylic acid (TCA) cycle enzymes, among them the most abundant housekeeping proteins of growing cells. Therefore, a comprehensive study on the regulation of glycolysis and the TCA cycle was initiated. Whereas expression of genes encoding the upper and lower parts of glycolysis (pgi, pfk, fbaA, and pykA) is not affected by the glucose supply, there is an activation of the glycolytic gap gene and the pgk operon by glucose. This activation seems to be dependent on the global regulator CcpA, as shown by 2D polyacrylamide gel electrophoresis analysis as well as by transcriptional analysis. Furthermore, a high glucose concentration stimulates production and excretion of organic acids (overflow metabolism) in the wild type but not in the ccpA mutant. Finally, CcpA is involved in strong glucose repression of almost all TCA cycle genes. In addition to TCA cycle and glycolytic enzymes, the levels of many other proteins are affected by the ccpA mutation. Our data suggest (i) that ccpA mutants are unable to activate glycolysis or carbon overflow metabolism and (ii) that CcpA might be a key regulator molecule, controlling a superregulon of glucose catabolism.

Urinary organic acid screening in children with developmental language delay.

The prevalence of 3-methylglutaconic aciduria was evaluated among children with developmental language disorders. A urine specimen was obtained from 40 children referred for developmental language delay to the Tel-Aviv Child Development Center during 12/96-6/97 and from 50 age-matched controls. Urine organic acids were analysed by gas chromatography-mass spectrometry. Urinary 3-methylglutaconic acid was quantified. A mildly increased excretion of 3-methylglutaconic acid was found in 8 children with developmental language delay. The combined excretion of 3-methylglutaconic and 3-methylglutaric acid was increased in 9 patients. There were no differences in the excretion of other organic acids. The patients with elevated 3-methylglutaconic acid did not differ from the other patients with developmental language disorders in any of the parameters evaluated. Mildly elevated urinary levels of 3-methylglutaconic acid may be a marker of a still undefined metabolic disorder presenting with developmental language delay. A further study in large groups of children with different developmental disorders is mandatory.

Formation of Propionate After Short-Term Ethanol Treatment and Its Interaction with the Carnitine Pool in Rat

Organic acidurias are genetic disorders of mitochondrial metabolism that lead to the accumulation in tissues and biological fluids of organic acids. It has been demonstrated that interaction of carnitine with the cellular CoA pool, through the production of acyl-carnitines, is potentially critical for maintaining normal cellular metabolism under conditions of impaired acyl-CoA use and that exposure of humans and other mammals to ethanol effects leads to impairment of mitochondrial function. The aim of the present study was to evaluate the role of ethanol on urinary excretion of short-chain organic acids and endogenous carnitines in rats. The data reported show that ethanol significantly increases urinary excretion of propionate, methylmalonate, as well as free acetate, butyrate, pyruvate, lactate, and β-hydroxybutyrate. Furthermore, the increased formation of propionate and methylmalonate was dependent on the dose of ethanol; did not require the metabolism of ethanol, as was shown in experiments with pyrazole treatment of ethanol rats; and appears to be mediated by beta-adrenergic mechanisms because propranolol almost completely suppresses propionate accumulation. Alcohol administration also increased excretion of specific acyl-carnitines, corresponding to the accumulating acyl groups, whereas excretion of free carnitine was significantly reduced, with respect to control values. The data presented indicate that the short-term ethanol administration is associated with increased excretion of selected organic acids. This study suggests that endogenous carnitine pool might play a role against the deleterious effects of accumulating short-chain organic acids.

Aminoaciduria resulting from vigabatrin administration in children with epilepsy

Vigabatrin (γ-vinyl gamma aminobutyric acid), a recently developed antiepileptic drug, has been extensively evaluated in the treatment of drug-resistant epilepsy. Several case reports demonstrated that vigabatrin affects urinary excretion of several amino and organic acids. Fourteen children were investigated for the presence of abnormal urinary amino acids before and after treatment with vigabatrin. All demonstrated increased urinary excretion of amino acids, particularly β-alanine, γ-aminobutyric acid, and β-amino-isobutyric acid while on vigabatrin, which were not detected when off medication. These results emphasize the importance of obtaining urine for metabolic evaluation before the administration of vigabatrin.