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Biochemistry and Molecular Biology... Mar 2018This article is a guided pedagogical approach, devoted to postgraduate students specializing in biochemistry, aimed at presenting all single reactions and overall...
This article is a guided pedagogical approach, devoted to postgraduate students specializing in biochemistry, aimed at presenting all single reactions and overall equations leading to the metabolic interaction between ureagenesis and citric acid cycle to be incorporated into a two-three lecture series about the interaction of urea cycle with other metabolic pathways. We emphasize that citrate synthetase, aconitase, and isocitrate dehydrogenase, three enzymes of the citric acid cycle are not involved, thus creating a shunt in citric acid cycle. In contrast, the glutamic-oxaloacetate transaminase, which does not belong to citric acid cycle, has a paramount importance in the metabolic interaction of the two cycles, because it generates aspartate, one of the two fuel molecules of urea cycle, and a-ketoglutarate, an intermediate of the citric acid cycle. Finally, students should appreciate that balancing equations for all atoms and charges is not only a stoichiometric task, but strongly facilitates the discussion of the physiological roles of metabolic pathways. Indeed, this exercise has been used in the classroom, to encourage a deeper level of understanding of an important biochemical issue. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(2):182-185, 2018.
Topics: Aspartate Aminotransferases; Biochemistry; Citric Acid Cycle; Students; Urea
PubMed: 29244243
DOI: 10.1002/bmb.21099 -
Chemistry (Weinheim An Der Bergstrasse,... Jun 2021Supramolecular hydrogels are useful in many areas such as cell culturing, catalysis, sensing, tissue engineering, drug delivery, environmental remediation and... (Review)
Review
Supramolecular hydrogels are useful in many areas such as cell culturing, catalysis, sensing, tissue engineering, drug delivery, environmental remediation and optoelectronics. The gels need specific properties for each application. The properties arise from a fibrous network that forms the matrix. A common method to prepare hydrogels is to use a pH change. Most methods result in a sudden pH jump and often lead to gels that are hard to reproduce and control. The urease-urea reaction can be used to control hydrogel properties by a uniform and controlled pH increase as well as to set up pH cycles. The reaction involves hydrolysis of urea by urease and production of ammonia which increases the pH. The rate of ammonia production can be controlled which can be used to prepare gels with differing properties. Herein, we show how the urease-urea reaction can be used for the construction of next generation functional materials.
Topics: Hydrogels; Hydrogen-Ion Concentration; Kinetics; Urea; Urease
PubMed: 33861488
DOI: 10.1002/chem.202100490 -
Journal of Veterinary Internal Medicine 1994Disposal of waste products accumulated during metabolic processes is integral to the health of any living organism. Disposal of excess nitrogen and ammonia is no... (Review)
Review
Disposal of waste products accumulated during metabolic processes is integral to the health of any living organism. Disposal of excess nitrogen and ammonia is no exception. Although nitrogen is essential for growth and maintenance in animals, an excess of some nitrogenous compounds can quickly lead to toxicity and death. Because of the correlation between ammonia accumulation and clinical disease, it is important for veterinary clinicians to understand the physiological mechanisms used to dispose of nitrogen and ammonia. Therefore, the purposes of this article are to review ammonia metabolism, the urea cycle, and the clinical implications of urea cycle dysfunction in diseases of companion animals.
Topics: Acid-Base Equilibrium; Ammonia; Animal Diseases; Animals; Glutamine; Liver; Urea
PubMed: 8046679
DOI: 10.1111/j.1939-1676.1994.tb03201.x -
Journal of Inherited Metabolic Disease Jan 2024Urea cycle defects (UCDs) are severe inherited metabolic diseases with high unmet needs which present a permanent risk of hyperammonaemic decompensation and subsequent... (Review)
Review
Urea cycle defects (UCDs) are severe inherited metabolic diseases with high unmet needs which present a permanent risk of hyperammonaemic decompensation and subsequent acute death or neurological sequelae, when treated with conventional dietetic and medical therapies. Liver transplantation is currently the only curative option, but has the potential to be supplanted by highly effective gene therapy interventions without the attendant need for life-long immunosuppression or limitations imposed by donor liver supply. Over the last three decades, pioneering genetic technologies have been explored to circumvent the consequences of UCDs, improve quality of life and long-term outcomes: adenoviral vectors, adeno-associated viral vectors, gene editing, genome integration and non-viral technology with messenger RNA. In this review, we present a summarised view of this historical path, which includes some seminal milestones of the gene therapy's epic. We provide an update about the state of the art of gene therapy technologies for UCDs and the current advantages and pitfalls driving future directions for research and development.
Topics: Humans; Ornithine Carbamoyltransferase Deficiency Disease; Liver Transplantation; Quality of Life; Urea; Living Donors; Genetic Therapy; Urea Cycle Disorders, Inborn
PubMed: 37026568
DOI: 10.1002/jimd.12609 -
Journal of Molecular Cell Biology Jul 2022O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains...
O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. O-GlcNAc transferase (OGT) and the opposing enzyme O-GlcNAcase (OGA) control this nutrient-sensing protein modification in cells. Here, we show that global O-GlcNAc levels are increased in multiple tissues of aged mice. In aged liver, carbamoyl phosphate synthetase 1 (CPS1) is among the most heavily O-GlcNAcylated proteins. CPS1 O-GlcNAcylation is reversed by calorie restriction and is sensitive to genetic and pharmacological manipulations of the O-GlcNAc pathway. High glucose stimulates CPS1 O-GlcNAcylation and inhibits CPS1 activity. Liver-specific deletion of OGT potentiates CPS1 activity and renders CPS1 irresponsive to further stimulation by a prolonged fasting. Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity.
Topics: Acetylglucosamine; Aging; Animals; Glycosylation; Liver; Mice; Protein Processing, Post-Translational; Urea
PubMed: 35285892
DOI: 10.1093/jmcb/mjac016 -
Journal of Molecular Cell Biology Jul 2022
Topics: Sugars; Urea
PubMed: 35460248
DOI: 10.1093/jmcb/mjac027 -
Biochemical Pharmacology Apr 2024The urea cycle (UC) is a critically important metabolic process for the disposal of nitrogen (ammonia) produced by amino acids catabolism. The impairment of this... (Review)
Review
The urea cycle (UC) is a critically important metabolic process for the disposal of nitrogen (ammonia) produced by amino acids catabolism. The impairment of this liver-specific pathway induced either by primary genetic defects or by secondary causes, namely those associated with hepatic disease or drug administration, may result in serious clinical consequences. Urea cycle disorders (UCD) and certain organic acidurias are the major groups of inherited rare diseases manifested with hyperammonemia (HA) with UC dysregulation. Importantly, several commonly prescribed drugs, including antiepileptics in monotherapy or polytherapy from carbamazepine to valproic acid or specific antineoplastic agents such as asparaginase or 5-fluorouracil may be associated with HA by mechanisms not fully elucidated. HA, disclosing an imbalance between ammoniagenesis and ammonia disposal via the UC, can evolve to encephalopathy which may lead to significant morbidity and central nervous system damage. This review will focus on biochemical mechanisms related with HA emphasizing some poorly understood perspectives behind the disruption of the UC and mitochondrial energy metabolism, namely: i) changes in acetyl-CoA or NAD levels in subcellular compartments; ii) post-translational modifications of key UC-related enzymes, namely acetylation, potentially affecting their catalytic activity; iii) the mitochondrial sirtuins-mediated role in ureagenesis. Moreover, the main UCD associated with HA will be summarized to highlight the relevance of investigating possible genetic mutations to account for unexpected HA during certain pharmacological therapies. The ammonia-induced effects should be avoided or overcome as part of safer therapeutic strategies to protect patients under treatment with drugs that may be potentially associated with HA.
Topics: Humans; Hyperammonemia; Ammonia; Liver Diseases; Urea
PubMed: 38307136
DOI: 10.1016/j.bcp.2024.116034 -
PloS One 2021Urea is a byproduct of the urea cycle in metabolism and is excreted through urine and sweat. Ammonia, which is toxic at low levels, is converted to the safe storage form...
Urea is a byproduct of the urea cycle in metabolism and is excreted through urine and sweat. Ammonia, which is toxic at low levels, is converted to the safe storage form of urea, which represents the largest efflux of nitrogen from many organisms. Urea is an important nitrogen source in agriculture, is added to many industrial products, and is a large component in wastewater. The enzyme urease hydrolyzes urea to ammonia and bicarbonate. This reaction is microbially mediated in soils, hydroponic solutions, and wastewater recycling and is catalyzed in vivo in plants using native urease, making measurement of urea environmentally important. Both direct and indirect methods to measure urea exist. This protocol uses diacetyl monoxime to directly determine the concentration of urea in solution. The protocol provides repeatable results and stable reagents with good color stability and simple measurement techniques for use in any lab with a spectrophotometer. The reaction between diacetyl monoxime and urea in the presence of sulfuric acid, phosphoric acid, thiosemicarbazide, and ferric chloride produces a chromophore with a peak absorbance at 520 nm and a linear relationship between concentration and absorbance from 0.4 to 5.0 mM urea in this protocol. The lack of detectable interferences makes this protocol suitable for the determination of millimolar levels of urea in wastewater streams and hydroponic solutions.
Topics: Colorimetry; Diacetyl; Urea; Urease
PubMed: 34748601
DOI: 10.1371/journal.pone.0259760 -
BMC Psychiatry Jul 2022Non-suicidal self-injury (NSSI) is an important symptom of bipolar disorder (BD) and other mental disorders and has attracted the attention of researchers lately. It is...
BACKGROUND
Non-suicidal self-injury (NSSI) is an important symptom of bipolar disorder (BD) and other mental disorders and has attracted the attention of researchers lately. It is of great significance to study the characteristic markers of NSSI. Metabolomics is a relatively new field that can provide complementary insights into data obtained from genomic, transcriptomic, and proteomic analyses of psychiatric disorders. The aim of this study was to identify the metabolic pathways associated with BD with NSSI and assess important diagnostic and predictive indices of NSSI in BD.
METHOD
Nuclear magnetic resonance spectrometry was performed to evaluate the serum metabolic profiles of patients with BD with NSSI (n = 31), patients with BD without NSSI (n = 46), and healthy controls (n = 10). Data were analyzed using an Orthogonal Partial Least Square Discriminant Analysis and a t-test. Differential metabolites were identified (VIP > 1 and p < 0.05), and further analyzed using Metabo Analyst 3.0 to identify associated metabolic pathways.
RESULTS
Eight metabolites in the serum and two important metabolic pathways, the urea and glutamate metabolism cycles, were found to distinguish patients with BD with NSSI from healthy controls. Eight metabolites in the serum, glycine and serine metabolism pathway, and the glucose-alanine cycle were found to distinguish patients with BD without NSSI from healthy controls. Five metabolites in the serum and the purine metabolism pathway were found to distinguish patients with BD with NSSI from those with BD without NSSI.
CONCLUSIONS
Abnormalities in the urea cycle, glutamate metabolism, and purine metabolism played important roles in the pathogenesis of BD with NSSI.
Topics: Biomarkers; Bipolar Disorder; Glutamates; Humans; Proteomics; Purines; Self-Injurious Behavior; Urea
PubMed: 35869468
DOI: 10.1186/s12888-022-04079-8 -
Immunity Dec 2019Integrating transcriptomic, proteomic, and metabolomic data, Lercher et al. show in a mouse model of LCMV infection that type I interferon alters the expression and...
Integrating transcriptomic, proteomic, and metabolomic data, Lercher et al. show in a mouse model of LCMV infection that type I interferon alters the expression and function of key enzymes of the urea cycle in hepatocytes. This results in altered systemic metabolism, attenuating antiviral T cell responses and ameliorating liver injury.
Topics: Animals; Antiviral Agents; Interferon Type I; Liver; Lymphocytic choriomeningitis virus; Mice; Proteomics; T-Lymphocytes; Urea
PubMed: 31951542
DOI: 10.1016/j.immuni.2019.11.012