Abstract:An experimental histidinemia was obtained in rats by in vivo administration of nitromethane, a histidase inhibitor. The magnitude of increase in plasma histidine in the nitromethane-treated rats was in the same range as that in the histidinemic subjects. No modifications were observed in the serotonin concentrations in blood or in various areas of brain between the nitromethane-treated rats and the control rats. No dramatic modifications of serotonin metabolism seem to be implicated in histidinemia, unlike phe… Show more
“…This suggests that epileptic seizures also induced other metabolic changes.Figure 5Metabolic networks ( A , B ) and representative physiological systems (C and D) containing the VOCs associated to kindled seizures. Transsulfation 30,32,35 , methionine-homocystaine cycle 38,39,61 , and histidine degradation 42,43 ( A ); fatty acid beta-oxidation networks and glycolysis 28,29,45,46 ( B ); epilepsy and anxiety 49,51,52,54 ( C ); and pheromones 34,50,56 ( D ). Abbreviations: 2-acetyl-pyrroline, 2AP; 5-formiminotetrahydrofolate, 5-formimino-THF; 5-methyltetrahydrofolate, 5-MTHF, aldehyde dehydrogenase 7 family member A1, ALDHTA1; betaine aldehyde dehydrogenase, BADH; cytochrome C oxidase subunit II, COX-2; 3,4-dehydro- exo -brevicomin, DEB; disulfide, dimethyl, DSDM; dimethyl trisulfide, DMTS; formimidoyltransferase cyclodeaminase, FTCD; gamma-aminobutyric acid, GABA; glutamate decarboxylase, GAD; hydrogen sulfide, H 2 S; histidine ammonia-lyase, HAL; phosphatidylcholine, PC; trimethylamine, TMA; 2,3,5-trithiahexane, TTH; vitamin B6, vB6.…”
Section: Discussionmentioning
confidence: 99%
“…5A). While methane, nitro- has not been detected in human blood, excretions such as urine and feces, or saliva, rats subcutaneously injected with methane, nitro- were used as a model of human histidinemia, showing increased levels of histidine in blood, urine, and cerebrospinal fluid, in which methane, nitro- is a histidine ammonia-lyase inhibitor (HAL) 42 . Furthermore, it is known that L-cysteine also inhibits HAL activity 43 .…”
Epilepsy is a chronic neurological disorder affecting mammals, including humans. Uncontrolled epilepsy is associated with poor quality of life, accidents, and sudden death. In particular, temporal lobe epilepsy (TLE) is the most common type of pharmacoresistant epilepsy, which easily gets out of control in human adults. The aim of this study was to profile urinary volatile organic compounds (VOCs) in a mouse model of TLE using solid-phase microextraction (SPME) gas chromatography mass spectrometry (GC-MS). Thirteen urinary VOCs exhibited differential abundance between epileptic and control mice, and the corresponding areas under the receiver operating characteristic (ROC) curve were greater than 0.8. Principal component analysis (PCA) based on these 13 VOCs separated epileptic from sham operated-mice, suggesting that all these 13 VOCs are epilepsy biomarkers. Promax rotation and dendrogram analysis concordantly separated the 13 VOCs into three groups. Stepwise linear discriminant analysis extracted methanethiol; disulfide, dimethyl; and 2-butanone as predictors. Based on known metabolic systems, the results suggest that TLE induced by amygdala stimulation could affect both endogenous metabolites and the gut flora. Future work will elucidate the physiological meaning of the VOCs as end-products of metabolic networks and assess the impact of the metabolic background involved in development of TLE.
“…This suggests that epileptic seizures also induced other metabolic changes.Figure 5Metabolic networks ( A , B ) and representative physiological systems (C and D) containing the VOCs associated to kindled seizures. Transsulfation 30,32,35 , methionine-homocystaine cycle 38,39,61 , and histidine degradation 42,43 ( A ); fatty acid beta-oxidation networks and glycolysis 28,29,45,46 ( B ); epilepsy and anxiety 49,51,52,54 ( C ); and pheromones 34,50,56 ( D ). Abbreviations: 2-acetyl-pyrroline, 2AP; 5-formiminotetrahydrofolate, 5-formimino-THF; 5-methyltetrahydrofolate, 5-MTHF, aldehyde dehydrogenase 7 family member A1, ALDHTA1; betaine aldehyde dehydrogenase, BADH; cytochrome C oxidase subunit II, COX-2; 3,4-dehydro- exo -brevicomin, DEB; disulfide, dimethyl, DSDM; dimethyl trisulfide, DMTS; formimidoyltransferase cyclodeaminase, FTCD; gamma-aminobutyric acid, GABA; glutamate decarboxylase, GAD; hydrogen sulfide, H 2 S; histidine ammonia-lyase, HAL; phosphatidylcholine, PC; trimethylamine, TMA; 2,3,5-trithiahexane, TTH; vitamin B6, vB6.…”
Section: Discussionmentioning
confidence: 99%
“…5A). While methane, nitro- has not been detected in human blood, excretions such as urine and feces, or saliva, rats subcutaneously injected with methane, nitro- were used as a model of human histidinemia, showing increased levels of histidine in blood, urine, and cerebrospinal fluid, in which methane, nitro- is a histidine ammonia-lyase inhibitor (HAL) 42 . Furthermore, it is known that L-cysteine also inhibits HAL activity 43 .…”
Epilepsy is a chronic neurological disorder affecting mammals, including humans. Uncontrolled epilepsy is associated with poor quality of life, accidents, and sudden death. In particular, temporal lobe epilepsy (TLE) is the most common type of pharmacoresistant epilepsy, which easily gets out of control in human adults. The aim of this study was to profile urinary volatile organic compounds (VOCs) in a mouse model of TLE using solid-phase microextraction (SPME) gas chromatography mass spectrometry (GC-MS). Thirteen urinary VOCs exhibited differential abundance between epileptic and control mice, and the corresponding areas under the receiver operating characteristic (ROC) curve were greater than 0.8. Principal component analysis (PCA) based on these 13 VOCs separated epileptic from sham operated-mice, suggesting that all these 13 VOCs are epilepsy biomarkers. Promax rotation and dendrogram analysis concordantly separated the 13 VOCs into three groups. Stepwise linear discriminant analysis extracted methanethiol; disulfide, dimethyl; and 2-butanone as predictors. Based on known metabolic systems, the results suggest that TLE induced by amygdala stimulation could affect both endogenous metabolites and the gut flora. Future work will elucidate the physiological meaning of the VOCs as end-products of metabolic networks and assess the impact of the metabolic background involved in development of TLE.
Histidemia, first described by Ghadimi in 1961, is caused by a defect in histidase. The defect results in elevated urinary excretion of histidine and its transamination products, and in high blood histidine. Blood histidine levels in histidinemic patients range from 290 to 1420 microM (normal 70-120 microM). The clinical picture of histidinemia varies from complete normality to severe retardation, with many patients being asymptomatic. No correlation has been found between clinical and biochemical data. Most reported cases have been identified in newborn screening programs. Frequency of histidinemia ranges from 1 in 8000 (Japan) to 1 in 37,000 (Sweden). Histidinemia is inherited as an autosomal recessive trait. Maternal histidinemia is believed to be benign. Studies in animal models have shown similar metabolic changes in animals and humans, but clinical changes differ. Histidinemia may be treated with a low-histidine diet, which reduces elevated histidine levels, although in most cases no improvement of clinical symptoms has been observed.
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