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IUBMB Life Jul 2018Glutathione was discovered in 1888, over 125 years ago. Since then, our understanding of various functions and metabolism of this important molecule has grown over these... (Review)
Review
Glutathione was discovered in 1888, over 125 years ago. Since then, our understanding of various functions and metabolism of this important molecule has grown over these years. But it is only now, in the last decade, that a somewhat complete picture of its metabolism has emerged. Glutathione metabolism has till now been largely depicted and understood by the γ-glutamyl cycle that was proposed in 1970. However, new findings and knowledge particularly on the transport and degradation of glutathione have revealed that many aspects of the γ-glutamyl cycle are incorrect. Despite this, an integrated critical analysis of the cycle has never been undertaken and this has led to the cycle and its errors perpetuating in the literature. This review takes a careful look at the γ-glutamyl cycle and its shortcomings and presents a "glutathione cycle" that captures the current understanding of glutathione metabolism. © 2018 IUBMB Life, 70(7):585-592, 2018.
Topics: Amino Acids; Animals; Bacteria; Biological Transport; Fungi; Glutamic Acid; Glutathione; Humans; Mammals; Metabolic Networks and Pathways; Plants; Pyrrolidonecarboxylic Acid; Yeasts; gamma-Glutamyltransferase
PubMed: 29667297
DOI: 10.1002/iub.1756 -
BMC Plant Biology Sep 2022Sugar beet is an important crop for sugar production. Sugar beet roots are stored up to several weeks post-harvest waiting for processing in the sugar factories. During...
BACKGROUND
Sugar beet is an important crop for sugar production. Sugar beet roots are stored up to several weeks post-harvest waiting for processing in the sugar factories. During this time, sucrose loss and invert sugar accumulation decreases the final yield and processing quality. To improve storability, more information about post-harvest metabolism is required. We investigated primary and secondary metabolites of six sugar beet varieties during storage. Based on their variety-specific sucrose loss, three storage classes representing well, moderate, and bad storability were compared. Furthermore, metabolic data were visualized together with transcriptome data to identify potential mechanisms involved in the storage process.
RESULTS
We found that sugar beet varieties that performed well during storage have higher pools of 15 free amino acids which were already observable at harvest. This storage class-specific feature is visible at harvest as well as after 13 weeks of storage. The profile of most of the detected organic acids and semi-polar metabolites changed during storage. Only pyroglutamic acid and two semi-polar metabolites, including ferulic acid, show higher levels in well storable varieties before and/or after 13 weeks of storage. The combinatorial OMICs approach revealed that well storable varieties had increased downregulation of genes involved in amino acid degradation before and after 13 weeks of storage. Furthermore, we found that most of the differentially genes involved in protein degradation were downregulated in well storable varieties at both timepoints, before and after 13 weeks of storage.
CONCLUSIONS
Our results indicate that increased levels of 15 free amino acids, pyroglutamic acid and two semi-polar compounds, including ferulic acid, were associated with a better storability of sugar beet taproots. Predictive metabolic patterns were already apparent at harvest. With respect to elongated storage, we highlighted the role of free amino acids in the taproot. Using complementary transcriptomic data, we could identify potential underlying mechanisms of sugar beet storability. These include the downregulation of genes for amino acid degradation and metabolism as well as a suppressed proteolysis in the well storable varieties.
Topics: Beta vulgaris; Plant Roots; Pyrrolidonecarboxylic Acid; Sucrose; Sugars
PubMed: 36076171
DOI: 10.1186/s12870-022-03784-6 -
Frontiers in Cellular and Infection... 2022Kidney stones or nephrolithiasis is a chronic metabolic disease characterized by renal colic and hematuria. Currently, a pathogenetic mechanism resulting in kidney stone...
BACKGROUND
Kidney stones or nephrolithiasis is a chronic metabolic disease characterized by renal colic and hematuria. Currently, a pathogenetic mechanism resulting in kidney stone formation remains elusive. We performed a multi-omic study investigating urinary microbial compositions and metabolic alterations during nephrolithiasis.
METHOD
Urine samples from healthy and individuals with nephrolithiasis were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectroscopy. Microbiome and metabolome profiles were analyzed individually and combined to construct interactome networks by bioinformatic analysis.
RESULTS
Distinct urinary microbiome profiles were determined in nephrolithiasis patients compared with controls. Thirty-nine differentially abundant taxa between controls and nephrolithiasis patients were identified, and Streptococcus showed the most significant enrichment in nephrolithiasis patients. We also observed significantly different microbial compositions between female and male nephrolithiasis patients. The metabolomic analysis identified 112 metabolites that were differentially expressed. Two significantly enriched metabolic pathways, including biosynthesis of unsaturated fatty acids and tryptophan metabolism, were also identified in nephrolithiasis patients. Four potentially diagnostic metabolites were also identified, including trans-3-hydroxycotinine, pyroglutamic acid, O-desmethylnaproxen, and FAHFA (16:0/18:2), and could function as biomarkers for the early diagnosis of nephrolithiasis. We also identified three metabolites that contributed to kidney stone size. Finally, our integrative analysis of the urinary tract microbiome and metabolome identified distinctly different network characteristics between the two groups.
CONCLUSIONS
Our study has characterized important profiles and correlations among urinary tract microbiomes and metabolomes in nephrolithiasis patients for the first time. These results shed new light on the pathogenesis of nephrolithiasis and could provide early clinical biomarkers for diagnosing the disease.
Topics: Biomarkers; Female; Humans; Kidney; Kidney Calculi; Male; Pyrrolidonecarboxylic Acid; RNA, Ribosomal, 16S; Tryptophan
PubMed: 36132987
DOI: 10.3389/fcimb.2022.953392 -
International Journal of Molecular... May 2021Genomic and phylogenetic analyses of various invertebrate phyla revealed the existence of genes that are evolutionarily related to the vertebrate's decapeptide... (Review)
Review
Genomic and phylogenetic analyses of various invertebrate phyla revealed the existence of genes that are evolutionarily related to the vertebrate's decapeptide gonadotropin-releasing hormone (GnRH) and the GnRH receptor genes. Upon the characterization of these gene products, encoding peptides and putative receptors, GnRH-related peptides and their G-protein coupled receptors have been identified. These include the adipokinetic hormone (AKH) and corazonin (CRZ) in insects and their cognate receptors that pair to form bioactive signaling systems, which network with additional neurotransmitters/hormones (e.g., octopamine and ecdysone). Multiple studies in the past 30 years have identified many aspects of the biology of these peptides that are similar in size to GnRH and function as neurohormones. This review briefly describes the main activities of these two neurohormones and their receptors in the fruit fly . The similarities and differences between AKH/CRZ and mammalian GnRH signaling systems are discussed. Of note, while GnRH has a key role in reproduction, AKH and CRZ show pleiotropic activities in the adult fly, primarily in metabolism and stress responses. From a protein evolution standpoint, the GnRH/AKH/CRZ family nicely demonstrates the developmental process of neuropeptide signaling systems emerging from a putative common ancestor and leading to divergent activities in distal phyla.
Topics: Amino Acid Sequence; Animals; Drosophila melanogaster; Evolution, Molecular; Gonadotropin-Releasing Hormone; Humans; Insect Hormones; Insect Proteins; Neuropeptides; Neurotransmitter Agents; Oligopeptides; Phylogeny; Pyrrolidonecarboxylic Acid; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 34068603
DOI: 10.3390/ijms22095035 -
The Journal of Biological Chemistry Jul 1948
Topics: Glutamic Acid; Humans; Pyrrolidonecarboxylic Acid
PubMed: 18871243
DOI: No ID Found -
Molecular Neurodegeneration Jun 2016Immunization against amyloid-β (Aβ) peptides deposited in Alzheimer's disease (AD) has shown considerable therapeutic effect in animal models however, the translation... (Review)
Review
Immunization against amyloid-β (Aβ) peptides deposited in Alzheimer's disease (AD) has shown considerable therapeutic effect in animal models however, the translation into human Alzheimer's patients is challenging. In recent years, a number of promising Aβ immunotherapy trials failed to reach primary study endpoints. Aside from uncertainties in the selection of patients and the start and duration of treatment, these results also suggest that the mechanisms underlying AD are still not fully understood. Thorough characterizations of protein aggregates in AD brain have revealed a conspicuous heterogeneity of Aβ peptides enabling the study of the toxic potential of each of the major forms. One such form, amino-terminally truncated and modified pyroglutamate (pGlu)-3 Aβ peptide appears to play a seminal role for disease initiation, qualifying it as novel target for immunotherapy approaches.
Topics: Alzheimer Disease; Alzheimer Vaccines; Amyloid beta-Protein Precursor; Animals; Humans; Pyrrolidonecarboxylic Acid
PubMed: 27363697
DOI: 10.1186/s13024-016-0115-2 -
Journal of Assisted Reproduction and... Dec 2022Polycystic ovary syndrome is a complex heterogeneous endocrine disorder associated with established metabolic abnormalities and is a common cause of infertility in...
PURPOSE
Polycystic ovary syndrome is a complex heterogeneous endocrine disorder associated with established metabolic abnormalities and is a common cause of infertility in females. Glutathione metabolism in the cumulus cells (CCs) of women with PCOS may be correlated to the quality of oocytes for infertility treatment; therefore, we used a metabolomics approach to examine changes in CCs from women with PCOS and oocyte quality.
METHODS
Among 135 women undergoing fertility treatment in the present study, there were 43 women with PCOS and 92 without. CCs were collected from the two groups and levels of pyroglutamic acid were measured using LC-MS/MS followed by qPCR and Western blot analysis to examine genes and proteins involved in pyroglutamic acid metabolism related to glutathione synthesis.
RESULTS
Women with PCOS showed increased levels of L-pyroglutamic acid, L-glutamate, and L-phenylalanine and decreased levels of Cys-Gly and N-acetyl-L-methionine. Gene expression of OPLAH, involved in pyroglutamic synthesis, was significantly increased in women with PCOS compared with those without. Gene expression of GSS was significantly decreased in women with PCOS and synthesis of glutathione synthetase protein was decreased. Expression of nuclear factor erythroid 2-related factor 2, involved in resistance to oxidative stress, was significantly increased in women with PCOS.
CONCLUSIONS
CCs of women with PCOS showed high concentrations of pyroglutamic acid and reduced glutathione synthesis, which causes oxidative stress in CCs, suggesting that decreased glutathione synthesis due to high levels of pyroglutamic acid in CCs may be related to the quality of oocytes in women with PCOS.
Topics: Humans; Female; Polycystic Ovary Syndrome; Cumulus Cells; Pyrrolidonecarboxylic Acid; Chromatography, Liquid; Tandem Mass Spectrometry; Oocytes; Infertility; Glutathione
PubMed: 36322230
DOI: 10.1007/s10815-022-02647-1 -
Annual Review of Entomology 2010The fat body plays major roles in the life of insects. It is a dynamic tissue involved in multiple metabolic functions. One of these functions is to store and release... (Review)
Review
The fat body plays major roles in the life of insects. It is a dynamic tissue involved in multiple metabolic functions. One of these functions is to store and release energy in response to the energy demands of the insect. Insects store energy reserves in the form of glycogen and triglycerides in the adipocytes, the main fat body cell. Insect adipocytes can store a great amount of lipid reserves as cytoplasmic lipid droplets. Lipid metabolism is essential for growth and reproduction and provides energy needed during extended nonfeeding periods. This review focuses on energy storage and release and summarizes current understanding of the mechanisms underlying these processes in insects.
Topics: Animals; Carbohydrate Metabolism; Energy Metabolism; Fat Body; Insect Hormones; Insecta; Lipid Metabolism; Oligopeptides; Pyrrolidonecarboxylic Acid
PubMed: 19725772
DOI: 10.1146/annurev-ento-112408-085356 -
Scientific Reports Mar 2017-Amino acids are enantiomers of L-amino acids and have recently been recognized as biomarkers and bioactive substances in mammals, including humans. In the present...
-Amino acids are enantiomers of L-amino acids and have recently been recognized as biomarkers and bioactive substances in mammals, including humans. In the present study, we investigated functions of the novel mammalian mitochondrial protein 9030617O03Rik and showed decreased expression under conditions of heart failure. Genomic sequence analyses showed partial homology with a bacterial aspartate/glutamate/hydantoin racemase. Subsequent determinations of all free amino acid concentrations in 9030617O03Rik-deficient mice showed high accumulations of D-glutamate in heart tissues. This is the first time that a significant amount of D-glutamate was detected in mammalian tissue. Further analysis of D-glutamate metabolism indicated that 9030617O03Rik is a D-glutamate cyclase that converts D-glutamate to 5-oxo-D-proline. Hence, this protein is the first identified enzyme responsible for mammalian D-glutamate metabolism, as confirmed in cloning analyses. These findings suggest that D-glutamate and 5-oxo-D-proline have bioactivities in mammals through the metabolism by D-glutamate cyclase.
Topics: Animals; Glutamic Acid; Hydro-Lyases; Mice; Mice, Knockout; Mitochondria, Heart; Mitochondrial Proteins; Pyrrolidonecarboxylic Acid
PubMed: 28266638
DOI: 10.1038/srep43911 -
Wiley Interdisciplinary Reviews.... Mar 2020Metabolic homeostasis is under strict regulation of humoral factors across various taxa. In particular, insulin and glucagon, referred to in Drosophila as Drosophila... (Review)
Review
Metabolic homeostasis is under strict regulation of humoral factors across various taxa. In particular, insulin and glucagon, referred to in Drosophila as Drosophila insulin-like peptides (DILPs) and adipokinetic hormone (AKH), respectively, are key hormones that regulate metabolism in most metazoa. While much is known about the regulation of DILPs, the mechanisms regulating AKH/glucagon production is still poorly understood. In this review, we describe the various factors that regulate the production of DILPs and AKH and emphasize the need for future studies to decipher how energy homeostasis is governed in Drosophila. This article is categorized under: Invertebrate Organogenesis > Flies Signaling Pathways > Global Signaling Mechanisms.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Glucagon; Homeostasis; Insect Hormones; Insulin; Oligopeptides; Pyrrolidonecarboxylic Acid; Signal Transduction
PubMed: 31379062
DOI: 10.1002/wdev.360