scholarly journals Analysis of the hibernation cycle using LC-MS-based metabolomics in ground squirrel liver

2009 ◽  
Vol 37 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Clark J. Nelson ◽  
Jessica P. Otis ◽  
Sandra L. Martin ◽  
Hannah V. Carey
Keyword(s):  
Lipid Metabolism ◽  
Small Molecules ◽  
Ground Squirrel ◽  
Metabolic Flexibility ◽  
Metabolic Depression ◽  
Amino Acid Catabolism ◽  
Pyrimidine Metabolism ◽  
Cholesterol Sulfate ◽  
Cofactor Metabolism ◽  
Insight Into

A hallmark of hibernation in mammals is metabolic flexibility, which is typified by reversible bouts of metabolic depression (torpor) and the seasonal shift from predominantly carbohydrate to lipid metabolism from summer to winter. To provide new insight into the control and consequences of hibernation, we used LC/MS-based metabolomics to measure differences in small molecules in ground squirrel liver in five activity states: summer, entering torpor, late torpor, arousing from torpor, and interbout arousal. There were significant alterations both seasonally and within torpor-arousal cycles in enzyme cofactor metabolism, amino acid catabolism, and purine and pyrimidine metabolism, with observed metabolites reduced during torpor and increased upon arousal. Multiple lipids also changed, including 1-oleoyllysophosphatidylcholine, cholesterol sulfate, and sphingosine, which tended to be lowest during torpor, and hexadecanedioic acid, which accumulated during a torpor bout. The results reveal the dramatic alterations that occur in several classes of metabolites, highlighting the value of metabolomic analyses in deciphering the hibernation phenotype.

scholarly journals Stochastic steps in secondary active sugar transport

2016 ◽  
Vol 113 (27) ◽  
pp. E3960-E3966 ◽  
Author(s):  
Joshua L. Adelman ◽  
Chiara Ghezzi ◽  
Paola Bisignano ◽  
Donald D. F. Loo ◽  
Seungho Choe ◽  
...  
Keyword(s):  
High Resolution ◽  
Small Molecules ◽  
Sugar Transport ◽  
Ion Binding ◽  
Sugar Transporter ◽  
Human Homolog ◽  
Domains Of Life ◽  
Insight Into ◽  
Stochastic Functional ◽  
Unique Capability

Secondary active transporters, such as those that adopt the leucine-transporter fold, are found in all domains of life, and they have the unique capability of harnessing the energy stored in ion gradients to accumulate small molecules essential for life as well as expel toxic and harmful compounds. How these proteins couple ion binding and transport to the concomitant flow of substrates is a fundamental structural and biophysical question that is beginning to be answered at the atomistic level with the advent of high-resolution structures of transporters in different structural states. Nonetheless, the dynamic character of the transporters, such as ion/substrate binding order and how binding triggers conformational change, is not revealed from static structures, yet it is critical to understanding their function. Here, we report a series of molecular simulations carried out on the sugar transporter vSGLT that lend insight into how substrate and ions are released from the inward-facing state of the transporter. Our simulations reveal that the order of release is stochastic. Functional experiments were designed to test this prediction on the human homolog, hSGLT1, and we also found that cytoplasmic release is not ordered, but we confirmed that substrate and ion binding from the extracellular space is ordered. Our findings unify conflicting published results concerning cytoplasmic release of ions and substrate and hint at the possibility that other transporters in the superfamily may lack coordination between ions and substrate in the inward-facing state.

scholarly journals Network Analysis Provides Insight into Tomato Lipid Metabolism

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 152 ◽  
Author(s):  
Anastasiya Kuhalskaya ◽  
Micha Wijesingha Ahchige ◽  
Leonardo Perez de Souza ◽  
José Vallarino ◽  
Yariv Brotman ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Network Analysis ◽  
Volatile Compounds ◽  
Tomato Fruit ◽  
Major Influence ◽  
Phenotypic Traits ◽  
Solanum Pennellii ◽  
Metabolic Network Analysis ◽  
Wide Range ◽  
Insight Into

Metabolic correlation networks have been used in several instances to obtain a deeper insight into the complexity of plant metabolism as a whole. In tomato (Solanum lycopersicum), metabolites have a major influence on taste and overall fruit quality traits. Previously a broad spectrum of metabolic and phenotypic traits has been described using a Solanum pennellii introgression-lines (ILs) population. To obtain insights into tomato fruit metabolism, we performed metabolic network analysis from existing data, covering a wide range of metabolic traits, including lipophilic and volatile compounds, for the first time. We provide a comprehensive fruit correlation network and show how primary, secondary, lipophilic, and volatile compounds connect to each other and how the individual metabolic classes are linked to yield-related phenotypic traits. Results revealed a high connectivity within and between different classes of lipophilic compounds, as well as between lipophilic and secondary metabolites. We focused on lipid metabolism and generated a gene-expression network with lipophilic metabolites to identify new putative lipid-related genes. Metabolite–transcript correlation analysis revealed key putative genes involved in lipid biosynthesis pathways. The overall results will help to deepen our understanding of tomato metabolism and provide candidate genes for transgenic approaches toward improving nutritional qualities in tomato.

scholarly journals Aberrant expression and DNA methylation of lipid metabolism genes in PCOS: a new insight into its pathogenesis

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Jie-Xue Pan ◽  
Ya-Jing Tan ◽  
Fang-Fang Wang ◽  
Ning-Ning Hou ◽  
Yu-Qian Xiang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lipid Metabolism ◽  
Aberrant Expression ◽  
Lipid Metabolism Genes ◽  
Insight Into

scholarly journals Metabolic flexibility during sleep

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Simeng Zhang ◽  
Yoshiaki Tanaka ◽  
Asuka Ishihara ◽  
Akiko Uchizawa ◽  
Insung Park ◽  
...  
Keyword(s):  
Young Adults ◽  
Time Resolution ◽  
Diurnal Rhythm ◽  
Indirect Calorimetry ◽  
Early Stage ◽  
Metabolic Flexibility ◽  
Extended Duration ◽  
Older Subjects ◽  
Metabolic Inflexibility ◽  
Insight Into

AbstractKnown as metabolic flexibility, oxidized substrate is selected in response to changes in the nutritional state. Sleep imposes an extended duration of fasting, and oxidized substrates during sleep were assumed to progressively shift from carbohydrate to fat, thereby gradually decreasing the respiratory quotient (RQ). Contrary to this assumption, whole-room indirect calorimetry with improved time resolution revealed that RQ re-ascended prior to awakening, and nadir of RQ in non-obese young adults occurred earlier in women than men after bedtime. The transient decrease in RQ during sleep was blunted in metabolically inflexible men with smaller amplitude of diurnal rhythm in RQ. Similarly, the effect of 10 years difference in age on RQ became significant during sleep; the decrease in RQ during sleep was blunted in older subjects. Inter-individual difference in RQ become apparent during sleep, and it might serve as a window to gain insight into the early-stage pathogenesis of metabolic inflexibility.

NMR spectroscopy in drug design

2001 ◽  
Vol 73 (9) ◽  
pp. 1429-1436 ◽  
Author(s):  
Markus Heller ◽  
Horst Kessler
Keyword(s):  
Small Molecules ◽  
Lead Optimization ◽  
Drug Candidate ◽  
Resonance Spectroscopy ◽  
Ligand Complex ◽  
New Techniques ◽  
Lead Finding ◽  
Efficient Screening ◽  
Insight Into

The process of preclinical drug discovery consists of two steps: finding of initial hits (binding ligands to a medicinal relevant target, usually a protein) and lead optimization. Nuclear magnetic resonance spectroscopy is a powerful tool that can provide valuable information to every step of drug development. NMR is commonly used for characterizing the structure and molecular dynamics of target or ligand molecules. During the structure-based lead optimization, NMR provides insight into the structural and dynamical properties of the target-ligand complex. Recently, the use of NMR in the lead finding process by screening technologies has been shown. For the latter use, new techniques have also been developed. Those techniques, in combination with high throughput, have lead to an efficient screening of libraries composed of small molecules. In this article, the role of NMR during the discovery of a drug candidate is described.

scholarly journals Insight into the mechanisms of action of estrogen receptor β in the breast, prostate, colon, and CNS

2013 ◽  
Vol 51 (3) ◽  
pp. T61-T74 ◽  
Author(s):  
Prasenjit Dey ◽  
Rodrigo P A Barros ◽  
Margaret Warner ◽  
Anders Ström ◽  
Jan-Åke Gustafsson
Keyword(s):  
Small Molecules ◽  
Kinase Inhibitor ◽  
Anxiety And Depression ◽  
Pharmaceutical Companies ◽  
Biological Processes ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinases ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Key Pathways ◽  
Insight Into

Estrogen and its receptors (ERs) influence many biological processes in physiology and pathology in men and women. ERs are involved in the etiology and/or progression of cancers of the prostate, breast, uterus, ovary, colon, lung, stomach, and malignancies of the immune system. In estrogen-sensitive malignancies, ERβ usually is a tumor suppressor and ERα is an oncogene. ERβ regulates genes in several key pathways including tumor suppression (p53, PTEN); metabolism (PI3K); survival (Akt); proliferation pathways (p45Skp2, cMyc, and cyclin E); cell-cycle arresting factors (p21WAF1, cyclin-dependent kinase inhibitor 1 (CDKN1A)), p27Kip1, and cyclin-dependent kinases (CDKs); protection from reactive oxygen species, glutathione peroxidase. Because they are activated by small molecules, ERs are excellent targets for pharmaceuticals. ERα antagonists have been used for many years in the treatment of breast cancer and more recently pharmaceutical companies have produced agonists which are very selective for ERα or ERβ. ERβ agonists are being considered for preventing progression of cancer, treatment of anxiety and depression, as anti-inflammatory agents and as agents, which prevent or reduce the severity of neurodegenerative diseases.

scholarly journals Lifespan-increasing drug nordihydroguaiaretic acid inhibits p300 and activates autophagy

2019 ◽  
Author(s):  
Tugsan Tezil ◽  
Manish Chamoli ◽  
Che-Ping Ng ◽  
Roman P. Simon ◽  
Victoria J. Butler ◽  
...  
Keyword(s):  
Small Molecules ◽  
Physiological Function ◽  
Nordihydroguaiaretic Acid ◽  
Mechanistic Insight ◽  
Epigenetic Regulator ◽  
Novel Target ◽  
Cellular Thermal Shift Assay ◽  
Insight Into ◽  
In Cells

AbstractAging is characterized by the progressive loss of physiological function in all organisms. Remarkably, the aging process can be modulated by environmental modifications, including diet and small molecules. The natural compound nordihydroguaiaretic acid (NDGA) robustly increases lifespan in flies and mice, but its mechanism of action remains unclear. Here, we report that NDGA is an inhibitor of the epigenetic regulator p300. We find that NDGA inhibits p300 acetyltransferase activity in vitro and suppresses acetylation of a key p300 target in histones (i.e., H3K27) in cells. We use the cellular thermal shift assay to uniquely demonstrate NDGA binding to p300 in cells. Finally, in agreement with recent findings indicating that p300 is a potent blocker of autophagy, we show that NDGA treatment induces autophagy. These findings identify p300 as a novel target of NDGA and provide mechanistic insight into its role in longevity.

scholarly journals Non-coding RNAs control metabolic state in mycobacteria

2019 ◽  
Author(s):  
Dolly Mehta ◽  
K Anjali ◽  
A Achuthan ◽  
Ritu Gupta ◽  
Arati Ramesh
Keyword(s):  
Lipid Metabolism ◽  
Cellular Response ◽  
Rna Binding ◽  
Translational Repression ◽  
Metabolic Flexibility ◽  
Redox Enzymes ◽  
Transcriptomic Response ◽  
Bacterial Signaling ◽  
Non Coding Rnas ◽  
Reductive Metabolism

ABSTRACTNon-coding RNAs play pivotal roles in bacterial signaling. However, RNAs from certain phyla (specially high-GC actinobacteria) remain elusive. Here, by revamping existing approaches we discover a family of structurally conserved RNAs in actinobacteria. These RNAs function by the recruiting ANTAR proteins to select transcripts; regulating them via translational repression. By overlapping with ORF start sites, these RNAs provide mechanisms by which even leader-less transcripts are regulated. In mycobacteria, transcripts marked by ANTAR-target RNAs are few but encode important redox enzymes especially involved in lipid metabolism. Notably, the cellular response to ANTAR-regulation is hierarchical, wherein immediate metabolic changes induced by ANTAR-RNA binding are amplified through a global transcriptomic response. This includes several genes from oxidative/reductive pathways; ultimately switching cells towards reductive metabolism. This discovery of ANTAR-target RNAs and associated regulation places RNAs as crucial players in controlling metabolic flexibility of mycobacteria, proposing a prominent role for ANTAR regulation across actinobacteria.

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