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Biochimica Et Biophysica Acta. Gene... Mar 2023Histone epigenetic modifications are chemical modification changes to histone amino acid residues that modulate gene expression without altering the DNA sequence. As... (Review)
Review
Histone epigenetic modifications are chemical modification changes to histone amino acid residues that modulate gene expression without altering the DNA sequence. As both the phenotypic and causal factors, cardiac metabolism disorder exacerbates mitochondrial ATP generation deficiency, thus promoting pathological cardiac hypertrophy. Moreover, several concomitant metabolic substrates also promote the expression of hypertrophy-responsive genes via regulating histone modifications as substrates or enzyme-modifiers, indicating their dual roles as metabolic and epigenetic regulators. This review focuses on the cardiac acetyl-CoA-dependent histone acetylation, NAD-dependent SIRT-mediated deacetylation, FAD-dependent LSD-mediated, and α-KG-dependent JMJD-mediated demethylation after briefly addressing the pathological and physiological cardiac energy metabolism. Besides using an "iceberg model" to explain the dual role of metabolic substrates as both metabolic and epigenetic regulators, we also put forward that the therapeutic supplementation of metabolic substrates is promising to blunt HF via re-establishing histone modifications.
Topics: Humans; Histones; Histone Code; Heart Failure; Protein Processing, Post-Translational; Methylation
PubMed: 36403753
DOI: 10.1016/j.bbagrm.2022.194898 -
Methods in Molecular Biology (Clifton,... 2021The efficacy, safety, and tolerability of drugs are dependent on numerous factors that influence their disposition. A dose that is efficacious and safe for one...
The efficacy, safety, and tolerability of drugs are dependent on numerous factors that influence their disposition. A dose that is efficacious and safe for one individual may result in sub-therapeutic or toxic blood concentrations in others. A significant source of this variability in drug response is drug metabolism, where differences in presystemic and systemic biotransformation efficiency result in variable degrees of systemic exposure (e.g., AUC, C, and/or C) following administration of a fixed dose.Interindividual differences in drug biotransformation have been studied extensively. It is recognized that both intrinsic factors (e.g., genetics, age, sex, and disease states) and extrinsic factors (e.g., diet , chemical exposures from the environment, and the microbiome) play a significant role. For drug-metabolizing enzymes, genetic variation can result in the complete absence or enhanced expression of a functional enzyme. In addition, upregulation and downregulation of gene expression, in response to an altered cellular environment, can achieve the same range of metabolic function (phenotype), but often in a less predictable and time-dependent manner. Understanding the mechanistic basis for variability in drug disposition and response is essential if we are to move beyond the era of empirical, trial-and-error dose selection and into an age of personalized medicine that will improve outcomes in maintaining health and treating disease.
Topics: Biotransformation; Cytochrome P450 Family 4; Gene Expression Regulation; Humans; Inactivation, Metabolic; Pharmaceutical Preparations; Pharmacogenomic Variants; Precision Medicine
PubMed: 34272705
DOI: 10.1007/978-1-0716-1554-6_17 -
Progress in Biophysics and Molecular... May 2023Glycometabolism is well known for its roles as the main source of energy, which mainly includes three metabolic pathways: oxidative phosphorylation, glycolysis and... (Review)
Review
Glycometabolism is well known for its roles as the main source of energy, which mainly includes three metabolic pathways: oxidative phosphorylation, glycolysis and pentose phosphate pathway. The orderly progress of glycometabolism is the basis for the maintenance of cardiovascular function. However, upon exposure to harmful stimuli, the intracellular glycometabolism changes or tends to shift toward another glycometabolism pathway more suitable for its own development and adaptation. This shift away from the normal glycometabolism is also known as glycometabolism reprogramming, which is commonly related to the occurrence and aggravation of cardiovascular diseases. In this review, we elucidate the physiological role of glycometabolism in the cardiovascular system and summarize the mechanisms by which glycometabolism drives cardiovascular diseases, including diabetes, cardiac hypertrophy, heart failure, atherosclerosis, and pulmonary hypertension. Collectively, directing GMR back to normal glycometabolism might provide a therapeutic strategy for the prevention and treatment of related cardiovascular diseases.
Topics: Humans; Cardiovascular Diseases; Glycolysis; Metabolic Networks and Pathways; Oxidative Phosphorylation; Cardiomegaly
PubMed: 36963725
DOI: 10.1016/j.pbiomolbio.2023.03.003 -
Plant Signaling & Behavior Mar 2021Gamma-aminobutyric acid (GABA) is a ubiquitous four-carbon, non-protein amino acid. GABA has been widely studied in animal central nervous systems, where it acts as an... (Review)
Review
Gamma-aminobutyric acid (GABA) is a ubiquitous four-carbon, non-protein amino acid. GABA has been widely studied in animal central nervous systems, where it acts as an inhibitory neurotransmitter. In plants, it is metabolized through the GABA shunt pathway, a bypass of the tricarboxylic acid (TCA) cycle. Additionally, it can be synthesized through the polyamine metabolic pathway. GABA acts as a signal in -mediated plant gene transformation and in plant development, especially in pollen tube elongation (to enter the ovule), root growth, fruit ripening, and seed germination. It is accumulated during plant responses to environmental stresses and pathogen and insect attacks. A high concentration of GABA elevates plant stress tolerance by improving photosynthesis, inhibiting reactive oxygen species (ROS) generation, activating antioxidant enzymes, and regulating stomatal opening in drought stress. The transporters of GABA in plants are reviewed in this work. We summarize the recent research on GABA function and transporters with the goal of providing a review of GABA in plants.
Topics: GABA Plasma Membrane Transport Proteins; Metabolic Networks and Pathways; Plants; Signal Transduction; Stress, Physiological; gamma-Aminobutyric Acid
PubMed: 33404284
DOI: 10.1080/15592324.2020.1862565 -
Cellular and Molecular Life Sciences :... Dec 2020The metabolic complexity and flexibility commonly observed in brain tumors, especially glioblastoma, is fundamental for their development and progression. The ability of... (Review)
Review
The metabolic complexity and flexibility commonly observed in brain tumors, especially glioblastoma, is fundamental for their development and progression. The ability of tumor cells to modify their genetic landscape and adapt metabolically, subverts therapeutic efficacy, and inevitably instigates therapeutic resistance. To overcome these challenges and develop effective therapeutic strategies targeting essential metabolic processes, it is necessary to identify the mechanisms underlying heterogeneity and define metabolic preferences and liabilities of malignant cells. In this review, we will discuss metabolic diversity in brain cancer and highlight the role of cancer stem cells in regulating metabolic heterogeneity. We will also highlight potential therapeutic modalities targeting metabolic vulnerabilities and examine how intercellular metabolic signaling can shape the tumor microenvironment.
Topics: Brain Neoplasms; Genetic Heterogeneity; Glioblastoma; Glycolysis; Humans; Metabolism; Neoplastic Stem Cells; Signal Transduction; Tumor Microenvironment
PubMed: 32506168
DOI: 10.1007/s00018-020-03569-w -
Frontiers in Endocrinology 2023The ability to generate thermogenic fat could be a targeted therapy to thwart obesity and improve metabolic health. Brown and beige adipocytes are two types of... (Review)
Review
The ability to generate thermogenic fat could be a targeted therapy to thwart obesity and improve metabolic health. Brown and beige adipocytes are two types of thermogenic fat cells that regulate energy balance. Both adipocytes share common morphological, biochemical, and thermogenic properties. Yet, recent evidence suggests unique features exist between brown and beige adipocytes, such as their cellular origin and thermogenic regulatory processes. Beige adipocytes also appear highly plastic, responding to environmental stimuli and interconverting between beige and white adipocyte states. Additionally, beige adipocytes appear to be metabolically heterogenic and have substrate specificity. Nevertheless, obese and aged individuals cannot develop beige adipocytes in response to thermogenic fat-inducers, creating a key clinical hurdle to their therapeutic promise. Thus, elucidating the underlying developmental, molecular, and functional mechanisms that govern thermogenic fat cells will improve our understanding of systemic energy regulation and strive for new targeted therapies to generate thermogenic fat. This review will examine the recent advances in thermogenic fat biogenesis, molecular regulation, and the potential mechanisms for their failure.
Topics: Humans; Aged; Adipocytes; Adipose Tissue, Brown; Adipocytes, Beige; Energy Metabolism; Obesity
PubMed: 37020585
DOI: 10.3389/fendo.2023.1150059 -
Cell Metabolism May 2024Effective responses against severe systemic infection require coordination between two complementary defense strategies that minimize the negative impact of infection on... (Review)
Review
Effective responses against severe systemic infection require coordination between two complementary defense strategies that minimize the negative impact of infection on the host: resistance, aimed at pathogen elimination, and disease tolerance, which limits tissue damage and preserves organ function. Resistance and disease tolerance mostly rely on divergent metabolic programs that may not operate simultaneously in time and space. Due to evolutionary reasons, the host initially prioritizes the elimination of the pathogen, leading to dominant resistance mechanisms at the potential expense of disease tolerance, which can contribute to organ failure. Here, we summarize our current understanding of the role of physiological perturbations resulting from infection in immune response dynamics and the metabolic program requirements associated with resistance and disease tolerance mechanisms. We then discuss how insight into the interplay of these mechanisms could inform future research aimed at improving sepsis outcomes and the potential for therapeutic interventions.
Topics: Sepsis; Humans; Animals; Infections; Metabolic Reprogramming
PubMed: 38513649
DOI: 10.1016/j.cmet.2024.02.013 -
Expert Opinion on Drug Metabolism &... 2022Cytochrome P450s (CYPs) are a superfamily of monooxygenases with diverse biological roles. CYP2J2 is an isozyme highly expressed in the heart where it metabolizes... (Review)
Review
INTRODUCTION
Cytochrome P450s (CYPs) are a superfamily of monooxygenases with diverse biological roles. CYP2J2 is an isozyme highly expressed in the heart where it metabolizes endogenous substrates such as N-3/N-6 polyunsaturated fatty acids (PUFA) to produce lipid mediators involved in homeostasis and cardioprotective responses. Expanding our knowledge of the role CYP2J2 has within the heart is important for understanding its impact on cardiac health and disease.
AREAS COVERED
The objective of this review was to assess the state of knowledge regarding cardiac CYP2J2. A literature search was conducted using PubMed-MEDLINE (from 2022 and earlier) to evaluate relevant studies regarding CYP2J2-mediated cardioprotection, small molecule modulators, effects of CYP2J2 substrates toward biologically relevant effects and implications of CYP2J2 polymorphisms and sexual dimorphism in the heart.
EXPERT OPINION
Cardiac CYP2J2-mediated metabolism of endogenous and exogenous substrates have been shown to impact cardiac function. Identifying individual factors, like sex and age, that affect CYP2J2 require further elucidation to better understand CYP2J2's clinical relevance. Resolving the biological targets and activities of CYP2J2-derived PUFA metabolites will be necessary to safely target CYP2J2 and design novel analogues. Targeting CYP2J2 for therapeutic aims offers a potential novel approach to regulating cardiac homeostasis, drug metabolism and cardioprotection.
Topics: Cytochrome P-450 CYP2J2; Cytochrome P-450 Enzyme System; Humans; Inactivation, Metabolic; Myocytes, Cardiac; Polymorphism, Genetic
PubMed: 35997132
DOI: 10.1080/17425255.2022.2114344 -
International Journal of Molecular... May 2022Cancer is the second most common cause of death worldwide after cardiovascular diseases. The development of molecular and biochemical techniques has expanded the... (Review)
Review
Cancer is the second most common cause of death worldwide after cardiovascular diseases. The development of molecular and biochemical techniques has expanded the knowledge of changes occurring in specific metabolic pathways of cancer cells. Increased aerobic glycolysis, the promotion of anaplerotic responses, and especially the dependence of cells on glutamine and fatty acid metabolism have become subjects of study. Despite many cancer treatment strategies, many patients with neoplastic diseases cannot be completely cured due to the development of resistance in cancer cells to currently used therapeutic approaches. It is now becoming a priority to develop new treatment strategies that are highly effective and have few side effects. In this review, we present the current knowledge of the enzymes involved in the different steps of glycolysis, the Krebs cycle, and the pentose phosphate pathway, and possible targeted therapies. The review also focuses on presenting the differences between cancer cells and normal cells in terms of metabolic phenotype. Knowledge of cancer cell metabolism is constantly evolving, and further research is needed to develop new strategies for anti-cancer therapies.
Topics: Citric Acid Cycle; Energy Metabolism; Glycolysis; Humans; Neoplasms; Pentose Phosphate Pathway
PubMed: 35628385
DOI: 10.3390/ijms23105572