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PubMed2006

The 5-lipoxygenase enzymatic pathway in the mouse brain: young versus old.

The 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism is an important source of inflammatory mediators, and is also present in the central nervous system. In this study, we assayed the expression levels and activity of 5-LO in different brain regions of young versus old C57Bl/6 mice. 5-LO mRNA was expressed in all the brain regions considered, i.e. cortex, hippocampus, and cerebellum. The highest expression level was observed in cerebellum compared with cortex and hippocampus, although it was not affected by aging. By contrast, 5-LO mRNA and protein levels were significantly increased in the hippocampus of old (25 months) versus young (3 months) mice. Finally, levels of the leukotriene B4, a metabolic product of 5-LO, were significantly increased in the hippocampus of old mice, but no difference was observed in cortex and cerebellum. These results demonstrate that the 5-LO enzymatic pathway is widely expressed in the mouse CNS, where significant changes are region-specific and age-dependent. This observation supports the hypothesis that 5-LO may be involved in diseases of the brain associated with aging.

Aging↗

PubMed2006

The production of polyhydroxyalkanoates in recombinant Escherichia coli.

Polyhydroxyalkanoates, the natural polyester that many microorganisms accumulate to store carbon and reducing equivalents, have been considered as a future alternative of traditional plastic due to their special properties. In Escherichia coli, a previous non-polyhydroxyalkanoates producer, pathway engineering has been developed as a very powerful approach to set up microbial production process through the introduction of direct genetic changes by recombinant DNA technology. Various metabolic pathways leading to the polyhydroxyalkanoates accumulation with desirable properties at low-cost and high-productivity have been developed. At the same time, high density fermentation technology of E. coli provides an efficient polyhydroxyalkanoates production strategy. This review focused on metabolic engineering, fermentation and downstream process aiming to polyhydroxyalkanoates production in E. coli.

Escherichia coli↗

PubMed2026

Genomic features, metabolism, and biotechnological applications of Candida tropicalis and other non-albicans Candida species.

The production of bio-based products by yeasts from agroindustrial byproducts is a key strategy for advancing circular bioeconomy. While Saccharomyces species remain the predominant industrial yeasts, their limited ability to assimilate lactose, pentoses, and glycerol, as well as their sensitivity to lignocellulose-derived inhibitors, restricts their efficient application in bioprocesses based on using industrial byproducts as fermentation media. In contrast, several non-albicans Candida species exhibit broad substrate utilization capacities and enhanced tolerance to industrial stresses, making them attractive candidates for the bioconversion of agroindustrial residues. This review critically examines recent advances in the genomic, metabolic, and physiological characterization of promising non-albicans Candida species, including Candida tropicalis, Candida parapsilosis, Candida viswanathii, Candida sojae, and Candida maltosa. Emphasis is given to genome-scale metabolic models, carbon assimilation pathways, stress-response mechanisms, and metabolic engineering approaches aiming at the production of value-added compounds. By identifying current achievements, knowledge gaps, and biotechnological bottlenecks, this review highlights the potential of these yeasts as emerging platforms for sustainable bioprocesses within a circular bioeconomy framework.

Biotechnology↗

PubMed2026

Research on identification of key genes and immune-metabolic mechanisms in atrial fibrillation through integrated multi-cohort transcriptomic analysis and machine learning.

This study aimed to integrate multiple datasets for the identification of atrial fibrillation (AF)-related differentially expressed genes (DEGs), analyze their underlying mechanisms through functional enrichment and machine learning, construct diagnostic models, and explore immune-metabolic interactions to provide novel biomarkers and theoretical foundations. Gene expression datasets were integrated and normalized, with batch effects removed using principal component analysis. Differential expression analysis, functional enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways), and machine learning-based feature gene selection and model construction were performed. Shapley additive explanations analysis was utilized to interpret the constructed models, while gene set enrichment analysis, gene set variation analysis, and immune cell infiltration analysis were conducted to investigate the associations between feature genes and immune infiltration. After integrating and normalizing gene expression data and eliminating batch effects via principal component analysis, 6 DEGs were identified, including 4 upregulated and 2 down-regulated ones. Functional enrichment analysis showed these DEGs were significantly enriched in neuro-related biological processes and pathways, indicating their key roles in AF pathogenesis. Five key feature genes were selected using LASSO, random forest, and support vector machine-recursive feature elimination algorithms. They had significant expression differences between the AF and control groups (P < .001) and were located on distinct chromosomes. The constructed random forest and support vector machine models performed excellently (area under the curve ≥ 0.85). Shapley additive explanations analysis revealed TNNI1 contributed most to model prediction, with its expression significantly positively correlated with immune cell infiltration. Gene set enrichment analysis and gene set variation analysis analyses further showed feature genes participated in AF pathogenesis by regulating immune modulation, metabolic pathways, and autophagy. Immune cell infiltration analysis found altered proportions of T-cell subsets and M0 macrophages in the AF group, along with complex links between feature gene expression and immune cell function. This study systematically elucidated the unique gene expression patterns and key regulatory pathways associated with AF, clarifying the crucial roles of feature genes in immune regulation, metabolic imbalance, and cellular dysfunction. These findings provide a theoretical basis and potential therapeutic targets for understanding AF pathogenesis and developing targeted treatment strategies.

Atrial Fibrillation↗

PubMed2003

Network-based analysis of metabolic regulation in the human red blood cell.

Reconstruction of cell-scale metabolic networks is now possible. A description of allowable metabolic network functions can be obtained using extreme pathways, which are the convex basis vectors of the solution space containing all steady state flux distributions. However, only a portion of these allowable network functions are physiologically possible due to kinetic and regulatory constraints. Methods are now needed that enable us to take a defined metabolic network and deduce candidate regulatory structures that control the selection of these physiologically relevant states. One such approach is the singular value decomposition (SVD) of extreme pathway matrices (P), which allows for the characterization of steady state solution spaces. Eigenpathways, which are the left singular vectors from the SVD of P, can be described and categorized by their biochemical function. SVD of P for the human red blood cell showed that the first five eigenpathways, out of a total of 23, effectively characterize all the relevant physiological states of red blood cell metabolism calculated with a detailed kinetic model. Thus, with five degrees of freedom the magnitude and nature of the regulatory needs are defined. Additionally, the dominant features of these first five eigenpathways described key metabolic splits that are indeed regulated in the human red blood cell. The extreme pathway matrix is derived directly from network topology and only knowledge of Vmax values is needed to reach these conclusions. Thus, we have implemented a network-based analysis of regulation that complements the study of individual regulatory events. This topological approach may provide candidate regulatory structures for metabolic networks with known stoichiometry but poorly characterized regulation.

Erythrocytes↗

PubMed2006

Degradation characteristics and metabolic pathway of 17alpha-ethynylestradiol by Sphingobacterium sp. JCR5.

A 17alpha-ethynylestradiol (EE2)-degrading bacterium was isolated from the activated sludge of the wastewater treatment plant (WWTP) of an oral contraceptives producing factory in Beijing, China. On the basis of its morphology, biochemical properties and the 16S rDNA sequence analysis, this strain was identified as Sphingobacterium sp. JCR5. This strain grew on EE2 as sole source of carbon and energy, and metabolized up to 87% of the substrate added (30 mgl-1) within 10 d at 30 degrees C. In addition to EE2 the strain could be cultivated on steroidal estrogens like estrone (E1), 17beta-estradiol (E2), estriol (E3) and mestranol (MeEE2), the intermediates of contraceptive medicine processing and on some aromatic compounds. Mass spectrum analysis of the EE2 degradation showed that in the first step it is oxygenized to E1, 2-hydroxy-2,4-dienevaleric acid and 2-hydroxy-2,4-diene-1,6-dioic acid, which are the main catabolic intermediates. The former was analogous to the pathway of a previously reported testosterone-degrading bacterium Comamonas testosteroni TA441 and the latter is a metabolite with a different cleavage position of 3-hydroxy-4,5-9,10-disecoestrane-1(10),2-diene-5,9,17-trione-4-oic acid from the former.

Ethinyl Estradiol↗

PubMed2026

hypeR-GEM: connecting metabolite signatures to enzyme-coding genes via genome-scale metabolic models.

MOTIVATION: Enrichment analysis is a cornerstone of "omics" data interpretation, enabling researchers to connect analysis results to biological processes and generate testable hypotheses. Enrichment analysis in metabolomics poses distinct challenges for interpretation and multi-omics integration due to the lack of well-defined and consistent connections to well-curated gene-centered biological knowledge repositories. To address these challenges, we developed hypeR-GEM, a methodology and associated R package that adapts gene set enrichment analysis to metabolomics. hypeR-GEM leverages genome-scale metabolic models (GEMs) to infer reaction-based links between metabolites and enzyme-coding genes, enabling the mapping of metabolite signatures to gene signatures and their subsequent annotation via gene set enrichment analysis. RESULTS: We validated hypeR-GEM using paired metabolomics-proteomics and metabolomics-transcriptomics datasets by assessing whether genes mapped from metabolites significantly overlapped with differentially expressed proteins or transcripts. We further evaluated whether pathways enriched via hypeR-GEM-mapped genes corresponded to those derived from paired proteomic or transcriptomic data. In most datasets analyzed, both the predicted enzyme-coding genes and the associated enriched pathways showed significant concordance with independently derived omics signatures, supporting the utility and robustness of hypeR-GEM. Finally, we applied hypeR-GEM to the analysis of age-associated metabolic signatures from the New England Centenarian Study. The results revealed consistent enrichment of lipid-related pathways, aligning with the well-established role of lipid metabolism in aging, and highlighted additional pathways not captured in the metabolites' annotation, demonstrating hypeR-GEM's practical utility in a real-world use case. AVAILABILITY AND IMPLEMENTATION: The hypeR-GEM R package, documentation, and workflow examples are freely available at https://github.com/montilab/hypeR-GEM and archived at https://doi.org/10.5281/zenodo.20586748.

Metabolomics↗

PubMed2006

Hydrogen metabolism in Shewanella oneidensis MR-1.

Shewanella oneidensis MR-1 is a facultative sediment microorganism which uses diverse compounds, such as oxygen and fumarate, as well as insoluble Fe(III) and Mn(IV) as electron acceptors. The electron donor spectrum is more limited and includes metabolic end products of primary fermenting bacteria, such as lactate, formate, and hydrogen. While the utilization of hydrogen as an electron donor has been described previously, we report here the formation of hydrogen from pyruvate under anaerobic, stationary-phase conditions in the absence of an external electron acceptor. Genes for the two S. oneidensis MR-1 hydrogenases, hydA, encoding a periplasmic [Fe-Fe] hydrogenase, and hyaB, encoding a periplasmic [Ni-Fe] hydrogenase, were found to be expressed only under anaerobic conditions during early exponential growth and into stationary-phase growth. Analyses of DeltahydA, DeltahyaB, and DeltahydA DeltahyaB in-frame-deletion mutants indicated that HydA functions primarily as a hydrogen-forming hydrogenase while HyaB has a bifunctional role and represents the dominant hydrogenase activity under the experimental conditions tested. Based on results from physiological and genetic experiments, we propose that hydrogen is formed from pyruvate by multiple parallel pathways, one pathway involving formate as an intermediate, pyruvate-formate lyase, and formate-hydrogen lyase, comprised of HydA hydrogenase and formate dehydrogenase, and a formate-independent pathway involving pyruvate dehydrogenase. A reverse electron transport chain is potentially involved in a formate-hydrogen lyase-independent pathway. While pyruvate does not support a fermentative mode of growth in this microorganism, pyruvate, in the absence of an electron acceptor, increased cell viability in anaerobic, stationary-phase cultures, suggesting a role in the survival of S. oneidensis MR-1 under stationary-phase conditions.

Hydrogen↗

PubMed2007

Monitoring diet effects via biofluids and their implications for metabolomics studies.

The effect of diet on metabolites found in rat urine samples has been investigated using nuclear magnetic resonance (NMR) and a new ambient ionization mass spectrometry experiment, extractive electrospray ionization mass spectrometry (EESI-MS). Urine samples from rats with three different dietary regimens were readily distinguished using multivariate statistical analysis on metabolites detected by NMR and MS. To observe the effect of diet on metabolic pathways, metabolites related to specific pathways were also investigated using multivariate statistical analysis. Discrimination is increased by making observations on restricted compound sets. Changes in diet at 24-h intervals led to predictable changes in the spectral data. Principal component analysis was used to separate the rats into groups according to their different dietary regimens using the full NMR, EESI-MS data or restricted sets of peaks in the mass spectra corresponding only to metabolites found in the urea cycle and metabolism of amino groups pathway. By contrast, multivariate analysis of variance from the score plots showed that metabolites of purine metabolism obscure the classification relative to the full metabolite set. These results suggest that it may be possible to reduce the number of statistical variables used by monitoring the biochemical variability of particular pathways. It should also be possible by this procedure to reduce the effect of diet in the biofluid samples for such purposes as disease detection.

Alloxan↗

PubMed2006

[Degradation pathway of 17alpha-ethynylestradiol by Sphingobacterium sp. JCR5].

A bacterial strain, JCR5, which degrades 17alpha-ethynylestradiol (EE2), was isolated from activated sludge of wastewater treatment plant treating wastewater from pharmacy factory mainly producing contraceptive medicine in Beijing, China. Based on its morphology, physiology biochemical properties and 16S rDNA sequence analysis, this strain was identified as Sphingobacteriumn sp. JCR5. Strain JCR5 can grow on EE2 as sole carbon and energy source. The degradation process for EE2 with initial concentration of 30 mg x L(-1) was studied, and the result indicated that the degradation rate of EE2 within 10 days was 87%. Experiments of different substrates showed that strain JCR5 can grow on many substrates other than EE2 such as several steroidal estrogens (estrone, 17beta-estradiol, estriol and mestranol), the intermediates in contraceptive medicine processing and some aromatic compounds. Mass spectrum analysis demonstrated that EE2 was oxygenized to estrone (E1) firstly, and 2-hydroxy-2,4-dienevaleric acid and 2-hydroxy-2,4-diene-1, 6-dioic acid were the main catabolic intermediates during EE2 degradation. The former adopted a pathway that was analogical to the pathway of the previously reported testosterone-degrading Comamnonas testosteroni TA441, and the latter was a metabolite with a different cleavage position of 3-hydroxy-4,5-9, 10-disecoestrane-1(10), 2-diene-5,9, 17- trione-4-oic acid from the former.

Biodegradation, Environmental↗

PubMed2005

PAR-2 activating peptide-induced stimulation of pregnant rat myometrium contractile activity partly involves the other membrane receptors.

OBJECTIVE: To study if spontaneous contractions augmented by proteinase-activated receptor-2 (PAR-2)-activating peptide serine-leucine-isoleucine-glycine-arginine-leucine (SLIGRL) involve coactivation of membrane chemoceptors and are associated with expression of PAR-2 mRNA in non-pregnant and pregnant rat myometrium. MATERIALS AND METHODS: Non-pregnant, mid-pregnant, and late pregnant rat uterine horn and small intestine segments were snap-frozen in liquid nitrogen to determine PAR-2 mRNA levels by real time polymerase chain reaction (PCR). Uterine rings were used for isometric tension recording. Effect of SLIGRL (0.1 mM) on spontaneous contractions before and after exposure to ibuprofen (cyclooxygenase inhibitor, 1.0 microM), SQ-29548 (thromboxane A(2) receptor inhibitor, 1.0 microM), ketotifen (histamine 1 receptor inhibitor, 10 microM), WEB-2170BS (platelet-activating factor (PAF) receptor inhibitor, 10 microM), atropine (muscarinic receptor inhibitor, 0.1 microM), or ketanserin (serotonin receptor inhibitor, 10 microM) were compared. Paired t-test and one-way ANOVA followed by Dunnett's or Newman-Keuls post hoc tests were used for statistical analysis when appropriate. SIGNIFICANCE: P<0.05. RESULTS: The agents did not significantly affect time-associated decay in spontaneous contractile activity in any group of the tissues. Activation of spontaneous contractions induced by SLIGRL in non-pregnant rat myometrium did not involve coactivation of membrane chemoceptors, while in mid-pregnant rat myometrium coactivation of prostanoid, histamine, and serotonin receptors and in late pregnant rat myometrium coactivation of thromboxane receptors was noted. Expression of PAR-2 mRNA was similar in non-pregnant, mid-pregnant, and late pregnant rat myometrium. CONCLUSIONS: Expression of PAR-2 in rat myometrium is not dependent on gestational age. Stimulation of PAR-2 is associated with production/release of cyclooxygenase pathway product(s) activating thromboxane/prostaglandin H2 receptors, partial involvement of histamine H1 receptors and serotonin receptors in midpregnancy and thromboxane A2/prostaglandin H2 receptors in late pregnancy.

Animals↗

PubMed2006

Genetic and biochemical characterization of the dioxygenase involved in lateral dioxygenation of dibenzofuran from Rhodococcus opacus strain SAO101.

Rhodococcus opacus strain SAO101 was shown to degrade on various polycyclic aromatic hydrocarbons such as naphthalene, dibenzofuran (DF), and dibenzo-p-dioxin (DD). One of the unique traits of the strain SAO101 is its ability to oxidize DF compounds by lateral dioxygenation. To clone the lateral dioxygenase gene involved in compound degradation in strain SAO101, we identified a cosmid clone that oxidizes aromatic compounds by using SAO101 genomic DNA. Sequencing analysis revealed that isolated cosmid clone contained ring-hydroxylating dioxygenase genes (narAaAb) with homologies to indene dioxygenase genes of Rhodococcus strain I24 and naphthalene dioxygenase genes of Rhodococcus strain NCIMB12038. The NarAaAb-expressing Rhodococcus cells exhibited broad substrate specificity for bicyclic aromatic compounds and had high ability to degrade dibenzofuran and naphthalene. Metabolite analysis revealed that dihydrodiol compounds were detected as metabolites from dibenzofuran by the NarAaAb-expressing Rhodococcus strain, indicating that dibenzofuran was converted by lateral dioxygenase activity of NarA dioxygenase. Based on reverse transcriptase-polymerase chain reaction analysis, it was found that the narAaAb genes were cotranscribed and that their expression was induced in the presence of aromatic hydrocarbon compounds. It is likely that these genes are involved in the degradation pathways of a wide range of aromatic hydrocarbons by this strain. Strain SAO101 harbors three huge linear plasmids, pWK301 (1,100 kbp), pWK302 (1,000 kbp), and pWK303 (700 kbp), and the nar genes were found to be located on the pWK301 plasmid.

Benzofurans↗

PubMed2006

Pathway confirmation and flux analysis of central metabolic pathways in Desulfovibrio vulgaris hildenborough using gas chromatography-mass spectrometry and Fourier transform-ion cyclotron resonance mass spectrometry.

Flux distribution in central metabolic pathways of Desulfovibrio vulgaris Hildenborough was examined using 13C tracer experiments. Consistent with the current genome annotation and independent evidence from enzyme activity assays, the isotopomer results from both gas chromatography-mass spectrometry (GC-MS) and Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) indicate the lack of an oxidatively functional tricarboxylic acid (TCA) cycle and an incomplete pentose phosphate pathway. Results from this study suggest that fluxes through both pathways are limited to biosynthesis. The data also indicate that >80% of the lactate was converted to acetate and that the reactions involved are the primary route of energy production [NAD(P)H and ATP production]. Independently of the TCA cycle, direct cleavage of acetyl coenzyme A to CO and 5,10-methyl tetrahydrofuran also leads to production of NADH and ATP. Although the genome annotation implicates a ferredoxin-dependent oxoglutarate synthase, isotopic evidence does not support flux through this reaction in either the oxidative or the reductive mode; therefore, the TCA cycle is incomplete. FT-ICR MS was used to locate the labeled carbon distribution in aspartate and glutamate and confirmed the presence of an atypical enzyme for citrate formation suggested in previous reports [the citrate synthesized by this enzyme is the isotopic antipode of the citrate synthesized by the (S)-citrate synthase]. These findings enable a better understanding of the relation between genome annotation and actual metabolic pathways in D. vulgaris and also demonstrate that FT-ICR MS is a powerful tool for isotopomer analysis, overcoming the problems with both GC-MS and nuclear magnetic resonance spectroscopy.

Acetyl Coenzyme A↗

PubMed2006

Chloroform degradation by butane-grown cells of Rhodococcus aetherovorans BCP1.

The ability of a Rhodococcus aetherovorans strain, BCP1, to grow on butane and to degrade chloroform in the 0-633 microM range (0-75.5 mg l(-1)) via aerobic cometabolism was investigated by means of resting-cell assays. BCP1 degraded chloroform with a complete mineralization of the organic Cl. The resulting butane and chloroform maximum specific degradation rates were equal to 118 and 22 micromol mg(protein)(-1)day(-1), respectively. Butane inhibition on chloroform degradation was satisfactorily interpreted by means of a model of competitive inhibition, with an inhibition constant equal to 38 % of the estimated butane half-saturation constant, whereas chloroform (at 11 microM) did not inhibit butane utilization. Acetylene (1,720 microM) induced an almost complete inactivation of the degradation of both butane and chloroform, indicating that the studied cometabolic process is mediated by a monooxygenase enzyme. BCP1 proved capable of degrading vinyl chloride and 1,1,2-trichloroethane, but not 1,2-trans-dichloroethylene. BCP1 could grow on the intermediates of the most common butane metabolic pathways and on the aliphatic hydrocarbons from ethane to n-heptane. After growth on n-hexane, it was able to deplete chloroform (13 microM) with a degradation rate higher than that obtained, at the same chloroform concentration, after growth on butane.

Binding, Competitive↗

PubMed2024

A pyruvate transporter in the apicoplast of apicomplexan parasites.

Pyruvate lies at a pivotal node of carbon metabolism in eukaryotes. It is involved in diverse metabolic pathways in multiple organelles, and its interorganelle shuttling is crucial for cell fitness. Many apicomplexan parasites harbor a unique organelle called the apicoplast that houses metabolic pathways like fatty acid and isoprenoid precursor biosyntheses, requiring pyruvate as a substrate. However, how pyruvate is supplied in the apicoplast remains enigmatic. Here, deploying the zoonotic parasite Toxoplasma gondii as a model apicomplexan, we identified two proteins residing in the apicoplast membranes that together constitute a functional apicoplast pyruvate carrier (APC) to mediate the import of cytosolic pyruvate. Depletion of APC results in reduced activities of metabolic pathways in the apicoplast and impaired integrity of this organelle, leading to parasite growth arrest. APC is a pyruvate transporter in diverse apicomplexan parasites, suggesting a common strategy for pyruvate acquisition by the apicoplast in these clinically relevant intracellular pathogens.

Apicoplasts↗

PubMed2006

Bacterial adaptation to high pressure: a respiratory system in the deep-sea bacterium Shewanella violacea DSS12.

Shewanella violacea DSS12 is a psychrophilic facultative piezophile isolated from the deep sea. In a previous study, we have shown that the bacterium adapted its respiratory components to alteration in growth pressure. This appears to be one of the bacterial adaptation mechanisms to high pressures. In this study, we measured the respiratory activities of S. violacea grown under various pressures. There was no significant difference between the cells grown under atmospheric pressure and a high pressure of 50 MPa relative to oxygen consumption of the cell-free extracts and inhibition patterns in the presence of KCN and antimycin A. Antimycin A did not inhibit the activity completely regardless of growth pressure, suggesting that there were complex III-containing and -eliminating pathways operating in parallel. On the other hand, there was a difference in the terminal oxidase activities. Our results showed that an inhibitor- and pressure-resistant terminal oxidase was expressed in the cells grown under high pressure. This property should contribute to the high-pressure adaptation mechanisms of S. violacea.

Adaptation, Physiological↗

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↗

PubMed2006

Thermodynamics-based metabolic flux analysis.

A new form of metabolic flux analysis (MFA) called thermodynamics-based metabolic flux analysis (TMFA) is introduced with the capability of generating thermodynamically feasible flux and metabolite activity profiles on a genome scale. TMFA involves the use of a set of linear thermodynamic constraints in addition to the mass balance constraints typically used in MFA. TMFA produces flux distributions that do not contain any thermodynamically infeasible reactions or pathways, and it provides information about the free energy change of reactions and the range of metabolite activities in addition to reaction fluxes. TMFA is applied to study the thermodynamically feasible ranges for the fluxes and the Gibbs free energy change, Delta(r)G', of the reactions and the activities of the metabolites in the genome-scale metabolic model of Escherichia coli developed by Palsson and co-workers. In the TMFA of the genome scale model, the metabolite activities and reaction Delta(r)G' are able to achieve a wide range of values at optimal growth. The reaction dihydroorotase is identified as a possible thermodynamic bottleneck in E. coli metabolism with a Delta(r)G' constrained close to zero while numerous reactions are identified throughout metabolism for which Delta(r)G' is always highly negative regardless of metabolite concentrations. As it has been proposed previously, these reactions with exclusively negative Delta(r)G' might be candidates for cell regulation, and we find that a significant number of these reactions appear to be the first steps in the linear portion of numerous biosynthesis pathways. The thermodynamically feasible ranges for the concentration ratios ATP/ADP, NAD(P)/NAD(P)H, and H(extracellular)(+)/H(intracellular)(+) are also determined and found to encompass the values observed experimentally in every case. Further, we find that the NAD/NADH and NADP/NADPH ratios maintained in the cell are close to the minimum feasible ratio and maximum feasible ratio, respectively.

Escherichia coli↗