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At least 19 recordsLinked to original sources
PubMed1976

A novel metabolic pathway in the metabolism of 5-(4'-chloro-n-butyl)picolinic acid.

The metabolism of 5-(4'-chloro-n-butyl)picolinic acid, which inhibits dopamine beta-hydroxylase and exhibits an antihypertensive effect, has been studied by gas chromatography mass spectrometry, utilising characteristic reaction products after derivatization. In rat urine five metabolities were identified by mass spectral analysis. It is found that four were elongated by a C2 unit in the carboxyl group at the 2-position on the pyridine ring and accounted for approximately 50% of the radioactivity in the 24 hour urine. The facts show that the metabolic pathway corresponding to the chain elongation of fatty acids is the major route of metabolism for this drug in the rat. Furthermore, this pathway would be confirmed in man, rabbit, guinea pig and mouse.

Animals↗
PubMed1992

Guanosine metabolism in adult rat cardiac myocytes: inhibition by acyclovir and analysis of a metabolic pathway.

The metabolic fate of transported guanosine was examined in adult rat cardiac myocytes. Freshly isolated cells were incubated with 50 microM 8-[3H]-guanosine and the purine nucleoside phosphorylase (PNP) inhibitor acyclovir, and the nucleotide products extracted and examined for radiolabel distribution. Acyclovir inhibited guanosine incorporation into the 5'-nucleotide pool up to 66%. The drug did not inhibit guanosine transport. Other experiments using 5'-[3H]-guanosine and 8-[14C]-guanosine in concert as metabolic tracers showed both tritium and radiocarbon in the guanine nucleotide products. We concluded from this study that both a kinase (probably adenosine kinase) and the enzyme pair purine nucleoside phosphorylase/hypoxanthine-guanine phosphoribosyltransferase are responsible for guanosine salvage in heart cells.

Acyclovir↗
PubMedDate not supplied

[Effect of an estrogen-progestin contraceptive preparation on the enzymatic acitivity of the pentosephosphate carbohydrate metabolic pathway and nucleic acid metabolic indices].

The effect of a long-term (14 days) combined introduction of mestranol and noiethinodrel in contraceptive doses on the activity of pentosophosphate routes enzymes of the carbohydrates metabolism, that of acid and basic ribonucleases and on the level of summary nucleinic acids in the uterus and liver in sexually mature female-rats was studied. It was found that the concentration of summary nucleinic acids in the tissues increases under the effect of the drug, the oxidative reactions enzymes become more active, while the activity of non-oxidative reactions enzymes of the pentosophosphate route and of acid and basic endoribonucleases in inhibited.

Animals↗
PubMed2026

Untargeted metabolomics reveals differential metabolic pathways and biomarkers in the acute phase of Kawasaki disease.

INTRODUCTION: Kawasaki disease (KD) is one of the most common rheumatic diseases in children and manifests with multisystem clinical features. Using untargeted metabolomics, our study investigated alterations in small-molecule metabolites in plasma of children with acute KD. Our study aimed to identify differential metabolic pathways and potential biomarkers. METHODS: Plasma samples were collected from 30 children diagnosed with KD and 30 age-matched healthy controls (HC) at Jinhua Maternal and Child Health Hospital between January 2025 and December 2025. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to analyse plasma samples. Enriched pathways were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and differential metabolic pathways were determined using MetaboAnalyst 5.0. Differential metabolites were screened using the nonparametric Mann-Whitney U-test and receiver operating characteristic curve area (AUC). The conservative average AUC from nested cross-validation was reported as the primary performance metric. Pearson correlation analysis was conducted to evaluate correlations between metabolites and clinical parameters. RESULTS: In total, 261 differential metabolites were identified between the KD and HC groups, including 87 lipids and lipid-like molecules, 69 organic heterocyclic compounds, 38 benzenoids, 34 organic acids, 14 phenylpropanoids, and 19 other compounds. Pathway analysis of these differential metabolites revealed 30 putatively enriched metabolic pathways for exploratory analysis. Of these pathways, primary bile acid biosynthesis, arginine biosynthesis, histidine metabolism, and phenylalanine-tyrosine-tryptophan biosynthesis were nominally associated with KD. Six metabolites with exploratory discriminatory performance (AUC > 0.8) were further identified: L-tyrosine, L-tryptophan, glutamine, histidine, histamine, and taurocholic acid. A combined model incorporating these metabolites achieved an apparent AUC of 0.984 in the full dataset; nested cross-validation yielded a more conservative AUC of 0.889 (95% CI 0.798-0.968), indicating promising exploratory discriminatory performance. CONCLUSION: Untargeted metabolomics enables identification of metabolically perturbed pathways during the acute phase of KD. L-tyrosine, L-tryptophan, glutamine, histidine, histamine, and taurocholic acid may serve as candidate biomarkers for acute phase of KD.

Kawasaki disease↗
PubMed1975

The biodegradation of some anionic detergents in the rat. A common metabolic pathway.

1. The metabolism of the anionic detergents potassium decyl [35S]sulphate and potassium octadecyl [35S]sulphate was investigated in the rat. 2. The major route for elimination of radioactivity was urinary regardless of the route of administration. 3. Both surfactants were extensively degraded in vivo to yield a common metabolite, butyric acid 4-[35S]sulphate, the major urinary radioactive component. 4. Whole-body radioautography revealed the liver as the major site of cellular accumulation of radioactivity following administration of either compound indicating the liver as the major site of metabolism. 5. It is suggested that alkyl sulphates with even-numbered carbons are degraded by a common pathway involving omega-oxidation followed by beta-oxidation.

Administration, Oral↗
PubMed1977

Specific metabolic pathway in vitro of pinazepam and diazepam by liver microsomal enzymes of different animal species.

The metabolic pathway of Pinazepam and Diazepam in vitro was studied with rat, guinea pig and dog liver microsomes using a chromatographic and spectrophotometric technique. Two main pathways were observed, N1-dealkylation and C3-hydroxylation. N1-dealkylation was shown to be the predominant reaction for Pinazepam in all the animal species studied, while C3-hydroxylation was the major metabolic pathway for Diazepam in the rat. No oxazepam was found when Pinazepam and Diazepam were incubated with liver microsomes.

Animals↗
PubMed1975

Normal activity of metabolic pathways involved in the formation and utilization of phosphoribosylpyrophosphate in erythrocytes of patients with primary metabolic gout.

The activity of metabolic pathways involved in the formation and utilization of phosphoribosylpyrophosphate (PRPP) was studied in. The erythrocytes of 34 patients with idiopathic metabolic gout. The activities of the oxidative pentose shunt, of the hypoxanthine-guanine and adenine phosphoribosyltransferases (HGPRT, APRT) and of PRPP synthetase, as well as the rates of PRPP generation and of adenine incorporation into nucleotides were found to be normal in the erythrocytes of all these patients. Four patients with metabolic gout due to enzymatic abnormalities, two relatives with partial deficiency of HGPRT and two relatives with mutant feedback-resistant PRPP synthetase, were studied for comparison. The significance of the results is discussed in relation to postulated mechanisms for purine overproduction in metabolic gout.

Adenine Phosphoribosyltransferase↗
PubMed2026

Metabolic pathways linked to sarcopenia in the Bushehr Elderly Health Program: kynurenine, nicotinamide, B-vitamins, and sulfur amino acids.

BACKGROUND: Sarcopenia, characterized by the loss of muscle mass and function, is a common condition in the elderly, associated with increased morbidity and mortality. Metabolic pathways, including the kynurenine, nicotinamide, B-vitamins, and sulfur amino acid pathways, may play a significant role in the development and progression of sarcopenia. This study investigates the relationship between metabolic pathways and sarcopenia, aiming to identify potential therapeutic targets. METHOD: Four hundred participants over 60 years were randomly selected from the second stage of the Bushehr Elderly Health Program (BEH). Frozen plasma samples were used to measure metabolomics. We used factor analysis and logistic regression analysis to determine the kynurenine-tryptophan metabolites associated with sarcopenia and its components. RESULT: Study participants included 89 sarcopenic subjects aged 72.92 ± 7.32 years and 307 non-sarcopenic subjects aged 68.12 ± 5.56 years. In full model adjustment, factor 3, which included methionine, tryptophan, 3-hydroxyanthranilic acid, picolinic acid, and xanthurenic acid, was associated with 38.3% lower risk of sarcopenia (OR = 0.617 [95%CI = 0.436–0.875]); Factor 6, which included methylmalonic acid and total homocysteine, was associated with a 33.7% increased risk of sarcopenia (OR = 1.337 [95%CI = 1.031–1.735]); and factor 7, consisting of nicotinamide, were related to a 25.2% lower risk of developing sarcopenia (OR = 0.748 [95%CI = 0.571–0.979]). Additionally, factor 1, which included quinolinic acid, kynurenine, 3-hydroxykynurenine, neopterin, kynurenic acid, anthranilic acid, cystathionine, and total cysteine, was linked to a 49.2% higher risk of low muscle strength, while factors 3 and 7 were associated with approximately a 24% decrease in risk of low muscle strength. Factors 5, consisting of serine and glycine, and factor 7 were related to 43% and 27.7% lower risk of low skeletal muscle index, respectively. While factor 6 was related to a 32.8% higher risk of low skeletal muscle index. Factor 1 was also related to a 32.9% higher risk of low walking speed, while factor 3 was related to a 28.5% lower risk of low walking speed. CONCLUSION: Specific metabolites from the kynurenine, nicotinamide, B-vitamin, and sulfur amino acid pathways are significantly associated with sarcopenia and its key parameters, such as muscle strength, skeletal muscle index, and walking speed. These findings suggest that metabolic profiling could offer valuable insights for early detection and targeted interventions for sarcopenia in elderly populations.

Humans↗
PubMed1992

Evolution of metabolic pathways by chance assembly of enzyme proteins generated from sense and antisense strands of pre-existing genes.

In order to get an insight into the evolutionary aspect of metabolic pathways, especially of the ubiquitous glycolytic pathway, we have carried out an extensive search of sense-sense and sense-antisense similarities for enzyme proteins in the glycolytic pathway, the pentose phosphate cycle, alcohol and lactate fermentation pathways and the TCA cycle. This investigation of amino acid sequences reveals a curious pattern of similarity relations; no similarity can be found between the enzyme proteins in a section of the glycolytic pathway where the glyceraldehyde-3-phosphate or even glycerol-3-phosphate is converted into the pyruvate while many examples of sense-sense and sense-antisense similarities are found even between enzyme proteins in distant blocks, e.g. between the proteins in the TCA cycle and those in the pentose phosphate cycle, as well as between the functionally associated proteins in each of these blocks. Complementary to this characteristic pattern of amino acid sequence similarity, the search for similarities of nucleotide sequences also finds that the similarities of glycolytic enzyme genes, some sense-sense and others sense-antisense similarities, are concentrated on the nucleotide sequences of prokaryotic 16S or eukaryotic 18S ribosomal RNA gene with its flanks, although some of the copy sequences are also found in transfer RNA genes as well as in 23S or 26S ribosomal RNA gene. These results strongly suggest that the metabolic pathways have been developed by the chance assembly of enzyme proteins generated from the sense and antisense strands of pre-existing genes, e.g. the fermentation pathways and pentose phosphate cycle by the proteins from the genes of enzymes in the glycolytic pathway and the TCA cycle from all these successively increased genes, ascribing the origin of metabolic enzyme genes to the close relation between the glycolytic enzyme protein genes and the RNA gene cluster.

Animals↗
PubMed1992

Metabolism of calcium antagonist Ro 40-5967: a case history of the use of diode-array u.v. spectroscopy and thermospray-mass spectrometry in the elucidation of a complex metabolic pathway.

1. The calcium antagonist, Ro 40-5967, is metabolized to a multitude of products by the rat and drug-related material is excreted predominantly via the bile. 2. Diode-array u.v. spectroscopy, following reverse phase h.p.l.c. separation of the partially purified metabolites, has been used to classify these compounds into six spectral classes which have been correlated with different metabolic reactions. 3. Connection of a mass spectrometer directly to the h.p.l.c. equipment by a thermospray interface, produced useful mass spectra. These, together with the u.v. spectra, enabled the structures of many metabolites to be elucidated. 4. Confirmation of structural assignments was provided by n.m.r. spectra of the major metabolites. 5. Major metabolic pathways included N-demethylation (16% of the biliary metabolites), hydrolysis of the ester side-chain (32%), hydroxylation at 4- (19%) and 5- (29%) positions of the benzimidazole ring, aromatization of the tetrahydronaphthyl system (26%), loss of the benzimidazole (15%) and glucuronidation of hydroxyl groups (81%).

Animals↗
PubMed2025

GhDMT7-mediated DNA methylation dynamics enhance starch and sucrose metabolism pathways to confer salt tolerance in cotton.

This study provides a comprehensive analysis of the impact of DNA methylation in cotton under salt stress conditions, elucidating its effects on gene expression and biological processes. Here, we determined the structures of the DNA methylation landscape across the cotton genome subjected to salt stress using whole-genome bisulfite sequencing (WGBS) and RNA-seq methodologies. We identified 4938 differentially methylated regions (DMRs) correlated with alterations in gene expression. Salt stress induced significant shifts in DNA methylation patterns, particularly in CHH contexts, suggesting context-dependent epigenetic regulation. DMRs were found to be implicated in diverse biological processes and pathways, encompassing protein metabolism, cellular homeostasis, starch and sucrose metabolism, and plant hormone signaling, all pivotal for cotton's adaptation to salt stress. Furthermore, RNA-seq analysis confirmed the impact of DNA methylation on gene expression, uncovering 9642 salt stress-responsive differentially expressed genes (DEGs). These DEGs exhibited enrichment in pathways such as carbohydrate metabolism, cell wall synthesis, and defense response, underscoring the intricate interplay between methylation and gene regulation in stress response. Moreover, the study investigated the role of the key DNA methyltransferase gene GhDMT7 in modulating cotton's response to salt stress, revealing that its downregulation enhanced cotton's salt tolerance, potentially attributed to decreased DNA methylation levels, reduced membrane damage, and enhanced antioxidant capacity. These findings elucidate the role of DNA methylation in abiotic stress resilience and provide insights for crop improvement.

Gossypium↗
PubMed1975

In vivo toxic effects of halothane on canine cerebral metabolic pathways.

The effects of high concentrations of halothane on cerebral metabolism were examined in dogs with the aid of an extracorporeal circuit to support the systemic circulation. At blood levels exceeding those representing equilibration with 2.3% halothane, a dose-related decrease in cerebral oxygen consumption (CMR02) occurred that was unrelated to the presence or absence of an active electroencephalogram. In this circumstance, despite adequate oxygen delivery, a dose-related alteration in oxidative phosphorylation also occurred as evidenced by progressive decreases in cerebral concentrations of ATP and phosphocreatine and concomitant increases in cerebral lactate and lactate/pyruvate ratio. These effects were totally reversible, except for persistence of increased of increased CMR02, after return to low halothane concentrations. It is concluded that the mechanisms of the cerebral metabolic effects of halothane differ from those of thiopental and, at high concentrations, are at least in part related to interference with oxidative phosphorylation. These in vivo studies confirm the potentially detrimental effects of high halothane concentrations on cerebral metabolic pathways as demonstrated by others in vitro.

Adenosine Triphosphate↗
PubMed1975

Incorporation into endogenous metabolic pathways of small fragments derived from I.C.I, 58,834(vioxazine).

1. Metabolic degradation of the tetrahydro-oxazine ring of 2-(2-ethoxyphenoxymethyl)-2,3,5,6-tetrahydro-1,4-oxazine (I.C.I. 58,834) gives rise to one- or two-carbon fragments which are utilized by endogenous metabolic pathways. 2. Evidence of this in dogs is shown by the 14C-labelled residues in tissues, 14C-labelled material in blood which has a half-life of three weeks, and elimination of [14C]urea in urine. 3. The same phenomenon occurs in rat, mouse and man, but to a smaller extent than in the dog. 4. Intravenous administration of [14C]ethanolamine to a dog gave rise to residual 14C blood levels with a half-life comparable to that produced by metabolic incorporation of 14C from 14C-I.C.I. 58,834.

Administration, Oral↗
PubMed1978

Study of the metabolic pathways of alprenolol in man and the dog using stable isotopes.

The metabolic pathways of alprenolol have been investigated in man and the dog, using an ion doublet technique of deuterium labelling combined with gas chromatography mass spectrometry. The drug is eliminated mainly by aromatic hydroxylation and glucuronidation. Specific analytical methods are applied to demonstrate that allylic oxidation and oxidative deamination are quantitatively of minor importance. The mechanism for oxidative deamination via an intermediary aldehyde could be elucidated by using the deuterium labelled compound. A method for characterization of 4-hydroxy-alprenolol glucuronides based on formation of stable derivatives and the following enzymatic hydrolysis is described. This approach has a general applicability to hydroxylated metabolites from compounds with an aminopropanol structure common for beta-adrenoceptor antagonists, for example. The metabolic routes for alprenolol in man and the dog are almost identical and in man more than 95% of a given dose can be accounted for.

Administration, Oral↗
PubMed1977

Purine and pyrimidine metabolism: pathways, pitfalls and perturbations.

The conceptual framework which underlies many studies of purine and pyrimidine metabolism in intact cells has been critically evaluated. The model that is implicit in many such studies is the single, partially purified enzyme. This paper gives examples both of instances in which the extrapolation of results of enzymes studies to intact cells has been successful and of instances in which enzymes behave differently in the intact cell than in cell extracts. Pitfalls in the extrapolation of results of enzyme studies to intact cells concern (a) metabolic pathways, (b) intracellular enzyme activities, (c) enzyme regulation, and (d) intracellular metabolite concentrations. Examples are also given of situations in which perturbations in one aspect of purine or pyrimidine metabolism lead to changes in other aspects, often distant in the network of reactions.

Adenine Phosphoribosyltransferase↗
PubMed1975

Enzyme activities of NADPH-forming metabolic pathways in normal and leukemic leukocytes.

With respect to the enzymes of NADPH-forming metabolic pathways in human leukocytes: (a) Glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) were less active in leukocytes (mostly myeloblasts) from eight patients with acute myeloblastic leukemia (I) than in leukocytes (mostly granulocytes) from 16 normal subjects (II). (b) Of the enzymes of the citrate cleavage pathway, ATP citrate lyase and malate dehydrogenase (decarboxylating) (NADP+) were virtually absent in the cells studied. (c) Isocitrate dehydrogenase (NADP+), aspartate aminotransferase, and alanine aminotransferase, which, together with the much more active malate dehydrogenase, constitute a newly proposed NADPH-forming metabolic cycle, showed a higher activity in I than in II or III, and therefore could compensate, as concerns NADPH-generation, for the low activity of pentose cycle dehydrogenases. We are not sure whether the enzymatic characteristic of I cells is attributable to their immaturity or to their leukemic nature.

ATP Citrate (pro-S)-Lyase↗