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Critical Reviews in Food Science and... 2015The biological differences between males and females are determined by a different set of genes and by a different reactivity to environmental stimuli, including the... (Review)
Review
The biological differences between males and females are determined by a different set of genes and by a different reactivity to environmental stimuli, including the diet, in general. These differences are further emphasized and driven by the exposure to a different hormone flux throughout the life. These differences have not been taken into appropriate consideration by the scientific community. Nutritional sciences are not immune from this "bias" and when nutritional needs are concerned, females are considered only when pregnant, lactating or when their hormonal profile is returning back to "normal," i.e., to the male-like profile. The authors highlight some of the most evident differences in aspects of biology that are associated with nutrition. This review presents and describes available data addressing differences and similarities of the "reference man" vs. the "reference woman" in term of metabolic activity and nutritional needs. According to this assumption, available evidences of sex-associated differences of specific biochemical pathways involved in substrate metabolism are reported and discussed. The modulation by sexual hormones affecting glucose, amino acid and protein metabolism and the metabolization of nutritional fats and the distribution of fat depots, is considered targeting a tentative starting up background for a gender concerned nutritional science.
Topics: Amino Acids; Body Composition; Diet; Dietary Carbohydrates; Dietary Proteins; Energy Metabolism; Fatty Acids; Female; Gonadal Steroid Hormones; Humans; Lactation; Male; Metabolism; Nutritional Physiological Phenomena; Polymorphism, Single Nucleotide; Pregnancy; Sex Characteristics; Sex Factors
PubMed: 24915409
DOI: 10.1080/10408398.2011.651177 -
Methods in Molecular Biology (Clifton,... 2023Cysteine-SILAC enables the detection and quantification of protein S-palmitoylation, an important protein posttranslational modification. Here we describe the cell...
Cysteine-SILAC enables the detection and quantification of protein S-palmitoylation, an important protein posttranslational modification. Here we describe the cell culture, protein extraction, selective enrichment, mass spectrometry, and data analysis for palmitoylated proteins from cell samples by this method.
Topics: Cysteine; Lipoylation; Mass Spectrometry; Protein Processing, Post-Translational; Proteins
PubMed: 36370270
DOI: 10.1007/978-1-0716-2863-8_5 -
Archives of Physiology and Biochemistry Oct 2014The interaction between antioxidant glutathione and the free thiol in susceptible cysteine residues of proteins leads to reversible protein S-glutathionylation. This... (Review)
Review
The interaction between antioxidant glutathione and the free thiol in susceptible cysteine residues of proteins leads to reversible protein S-glutathionylation. This reaction ensures cellular homeostasis control (as a common redox-dependent post-translational modification associated with signal transduction) and intervenes in oxidative stress-related cardiovascular pathology (as initiated by redox imbalance). The purpose of this review is to evaluate the recent knowledge on protein S-glutathionylation in terms of chemistry, broad cellular intervention, specific quantification, and potential for therapeutic exploitation. The data bases searched were Medline and PubMed, from 2009 to 2014 (term: glutathionylation). Protein S-glutathionylation ensures protection of protein thiols against irreversible over-oxidation, operates as a biological redox switch in both cell survival (influencing kinases and protein phosphatases pathways) and cell death (by potentiation of apoptosis), and cross-talks with phosphorylation and with S-nitrosylation. Collectively, protein S-glutathionylation appears as a valuable biomarker for oxidative stress, with potential for translation into novel therapeutic strategies.
Topics: Animals; Glutathione; Humans; Oxidative Stress; Protein Processing, Post-Translational; Proteins; Sulfhydryl Compounds
PubMed: 25112365
DOI: 10.3109/13813455.2014.944544 -
Journal of Proteome Research Jan 2021Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization,... (Review)
Review
Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization, activity, stability, and complex formation. The deregulation of protein -acylation contributes to many diseases such as cancer and neurodegenerative disorders. The past decade has witnessed substantial progress in proteomic analysis of protein -acylation, which significantly advanced our understanding of -acylation biology. In this review, we summarized the techniques for the enrichment of -acylated proteins or peptides, critically reviewed proteomic studies of protein -acylation at eight different levels, and proposed major challenges for the -acylproteomics field. In summary, proteome-scale analysis of protein -acylation comes of age and will play increasingly important roles in discovering new disease mechanisms, biomarkers, and therapeutic targets.
Topics: Acylation; Lipoylation; Protein S; Proteome; Proteomics
PubMed: 33253586
DOI: 10.1021/acs.jproteome.0c00409 -
International Journal of Molecular... Dec 2016Enhanced proliferation and survival are common features of cancer cells. Cancer cells are metabolically reprogrammed which aids in their survival in nutrient-poor... (Review)
Review
Enhanced proliferation and survival are common features of cancer cells. Cancer cells are metabolically reprogrammed which aids in their survival in nutrient-poor environments. Indeed, changes in metabolism of glucose and glutamine are essential for tumor progression. Thus, metabolic reprogramming is now well accepted as a hallmark of cancer. Recent findings suggest that reprogramming of lipid metabolism also occurs in cancer cells, since lipids are used for biosynthesis of membranes, post-translational modifications, second messengers for signal transduction, and as a source of energy during nutrient deprivation. The tumor suppressor p53 is a transcription factor that controls the expression of proteins involved in cell cycle arrest, DNA repair, apoptosis, and senescence. p53 also regulates cellular metabolism, which appears to play a key role in its tumor suppressive activities. In this review article, we summarize non-canonical functions of wild-type and mutant p53 on lipid metabolism and discuss their association with cancer progression.
Topics: Animals; Humans; Lipid Metabolism; Mutant Proteins; Neoplasm Proteins; Neoplasms; Tumor Suppressor Protein p53
PubMed: 27973397
DOI: 10.3390/ijms17122074 -
Applied and Environmental Microbiology Apr 2019Thioredoxins are small proteins that regulate the cellular redox state, prevent oxidative damage, and play an active role in cell repair. Oxidative stress has proven to...
Thioredoxins are small proteins that regulate the cellular redox state, prevent oxidative damage, and play an active role in cell repair. Oxidative stress has proven to be of much relevance in biotechnological processes when the metabolism of is mainly respiratory. During wine yeast starter production, active dry yeast cytosolic thioredoxin Trx2p is a key player in protecting metabolic enzymes from being oxidized by carbonylation. Less is known about the role of redox control during grape juice fermentation. A mutant strain that lacked both cytosolic thioredoxins, Trx1p and Trx2p, was tested for grape juice fermentation. Its growth and sugar consumption were greatly impaired, which indicates the system's relevance under fermentative conditions. A proteomic analysis indicated that deletion of the genes and caused a reduction in the ribosomal proteins and factors involved in translation elongation in addition to enzymes for glycolysis and amino acid biosynthesis. A metabolomic analysis of the Δ Δ mutant showed an increase in most proteogenic amino acids, phospholipids, and sphingolipids and higher fatty acid desaturase Ole1p content. Low glycolytic activity was behind the reduced growth and fermentative capacity of the thioredoxin deletion strain. All three hexokinases were downregulated in the mutant strain, but total hexokinase activity remained, probably due to posttranslational regulation. Pyruvate kinase Cdc19p presented an early level of aggregation in the Δ Δ mutant, which may contribute to a diminished hexose metabolism and trigger regulatory mechanisms that could influence the level of glycolytic enzymes. Oxidative stress is a common hazardous condition that cells have to face in their lifetime. Oxidative damage may diminish cell vitality and viability by reducing metabolism and eventually leading to aging and ultimate death. Wine yeast also faces oxidative attack during its biotechnological uses. One of the main yeast antioxidant systems involves two small proteins called thioredoxins. When these two proteins are removed, wine yeast shows diminished growth, protein synthesis, and sugar metabolism under wine-making conditions, and amino acid and lipid metabolism are also affected. Altogether, our results indicate that proper redox regulation is a key factor for metabolic adaptations during grape juice fermentation.
Topics: Cytosol; Fermentation; Gene Deletion; Glycolysis; Lipid Metabolism; Membrane Proteins; Metabolomics; Oxidation-Reduction; Oxidative Stress; Peroxiredoxins; Protein Biosynthesis; Proteomics; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Thioredoxins; Vitis; Wine
PubMed: 30683739
DOI: 10.1128/AEM.02953-18 -
Pharmacology & Therapeutics Jun 2019Adhesion G-protein coupled receptors (aGPCRs) are emerging as important actors in energy homeostasis. Recent biochemical and functional studies using transgenic mice... (Review)
Review
Adhesion G-protein coupled receptors (aGPCRs) are emerging as important actors in energy homeostasis. Recent biochemical and functional studies using transgenic mice indicate that aGPCRs play important roles in endocrine and metabolic functions including β-cell differentiation, insulin secretion, adipogenesis and whole body fuel homeostasis. Most aGPCRs are orphans, for which endogenous ligands have not yet been identified, and many of the endogenous ligands of the already de-orphanised aGPCRs are components of the extracellular matrix (ECM). In this review we focus on aGPCR expression in metabolically active tissues, their activation by ECM proteins, and current knowledge of their potential roles in islet development, insulin secretion, adipogenesis and muscle function.
Topics: Animals; Energy Metabolism; Humans; Receptors, G-Protein-Coupled
PubMed: 30825474
DOI: 10.1016/j.pharmthera.2019.02.012 -
European Journal of Drug Metabolism and... Apr 2016Amino-noscapine is a promising noscapine derivative undergoing R&D as an efficient anti-tumor drug. In vitro phase I metabolism incubation system was employed. In vitro...
Amino-noscapine is a promising noscapine derivative undergoing R&D as an efficient anti-tumor drug. In vitro phase I metabolism incubation system was employed. In vitro samples were analyzed using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. In vitro recombinant CYP isoforms screening was used to identify the drug-metabolizing enzymes involved in the metabolism of amino-noscapine. Multiple metabolics were formed, including the formation of metabolite undergoing cleavage of methylenedioxy group, hydroxylated metabolites, demethylated metabolites, and metabolites undergoing C-C cleavage. Nearly, all the CYP isoforms were involved in the metabolism of metabolites II, III, VII, IX, and X. CYP1A1 was demonstrated to be the major CYP isoform for the formation of metabolites IV and V. CYP1A1 and CYP3A4 mainly catalyzed the formation of metabolite VI. The metabolic formation of VIII was mainly catalyzed by CYP2C19 and CYP3A4. CYP3A4 was the main enzyme for the formation of XI. CYP2C9 mainly catalyzed the generation of metabolite XII. In conclusion, the metabolic pathway of amino-noscapine was elucidated in the present study using in vitro phase I incubation experiment, including the structural elucidation of metabolites and involved phase I drug-metabolizing enzymes. This information was helpful for the R&D of amino-noscapine.
Topics: Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Humans; Metabolic Detoxication, Phase I; Microsomes, Liver; Noscapine; Spectrometry, Mass, Electrospray Ionization
PubMed: 25527252
DOI: 10.1007/s13318-014-0241-6 -
Free Radical Biology & Medicine Sep 2007Protein S-glutathionylation, the reversible formation of mixed disulfides between glutathione and low-pKa cysteinyl residues, not only is a cellular response to mild... (Review)
Review
Protein S-glutathionylation, the reversible formation of mixed disulfides between glutathione and low-pKa cysteinyl residues, not only is a cellular response to mild oxidative/nitrosative stress, but also occurs under basal (physiological) conditions. S-glutathionylation has now emerged as a potential mechanism for dynamic, posttranslational regulation of a variety of regulatory, structural, and metabolic proteins. Moreover, substantial recent studies have implicated S-glutathionylation in the regulation of signaling and metabolic pathways in intact cellular systems. The growing list of S-glutathionylated proteins, in both animal and plant cells, attests to the occurrence of S-glutathionylation in cellular response pathways. The existence of antioxidant enzymes that specifically regulate S-glutathionylation would emphasize its importance in modulating protein function, suggesting that this protein modification too might have a role in cell signaling. The continued development of proteomic and analytical methods for disulfide analysis will help us better understand the full extent of the roles these modifications play in the regulation of cell function. In this review, we describe recent breakthroughs in our understanding of the potential role of protein S-glutathionylation in the redox regulation of signal transduction.
Topics: Animals; Glutathione Disulfide; Humans; Oxidation-Reduction; Proteins; Sulfhydryl Compounds
PubMed: 17697933
DOI: 10.1016/j.freeradbiomed.2007.06.014 -
The Journal of Cell Biology Feb 2022Arsenic is an environmental toxin that exists mainly as pentavalent arsenate and trivalent arsenite. Both forms activate the yeast SAPK Hog1 but with different...
Arsenic is an environmental toxin that exists mainly as pentavalent arsenate and trivalent arsenite. Both forms activate the yeast SAPK Hog1 but with different consequences. We describe a mechanism by which cells distinguish between these arsenicals through one-step metabolism to differentially regulate the bidirectional glycerol channel Fps1, an adventitious port for arsenite. Cells exposed to arsenate reduce it to thiol-reactive arsenite, which modifies a set of cysteine residues in target proteins, whereas cells exposed to arsenite metabolize it to methylarsenite, which modifies an additional set of cysteine residues. Hog1 becomes arsenylated, which prevents it from closing Fps1. However, this block is overcome in cells exposed to arsenite through methylarsenylation of Acr3, an arsenite efflux pump that we found also regulates Fps1 directly. This adaptation allows cells to restrict arsenite entry through Fps1 and also allows its exit when produced from arsenate exposure. These results have broad implications for understanding how SAPKs activated by diverse stressors can drive stress-specific outputs.
Topics: Arsenicals; Arsenites; Biological Transport; Membrane Proteins; Models, Biological; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 35139143
DOI: 10.1083/jcb.202109034