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Zhongguo Dang Dai Er Ke Za Zhi =... Apr 2023The male neonate in this case study was admitted to the hospital at 15 hours of age due to respiratory distress for 15 hours and poor response for 3 hours after...
The male neonate in this case study was admitted to the hospital at 15 hours of age due to respiratory distress for 15 hours and poor response for 3 hours after resuscitation from asphyxia. The neonate was highly unresponsive, with central respiratory failure and seizures. Serum ammonia was elevated (>1 000 μmol/L). Blood tandem mass spectrometry revealed a significant decrease in citrulline. Rapid familial whole genome sequencing revealed gene mutations inherited from the mother. Continuous hemodialysis filtration and other treatments were given. Neurological assessment was performed by cranial magnetic resonance imaging and electroencephalogram. The neonate was diagnosed with ornithine transcarbamylase deficiency combined with brain injury. He died at 6 days of age after withdrawing care. This article focuses on the differential diagnosis of neonatal hyperammonemia and introduces the multidisciplinary management of inborn error of metabolism.
Topics: Humans; Infant, Newborn; Male; Citrulline; Electroencephalography; Hyperammonemia; Ornithine Carbamoyltransferase Deficiency Disease; Seizures
PubMed: 37073851
DOI: 10.7499/j.issn.1008-8830.2302023 -
International Journal of Molecular... Nov 2022Accumulating evidence are available on the involvement of l-arginine-nitric oxide (NO) system in complex biological processes and numerous clinical conditions.... (Review)
Review
Accumulating evidence are available on the involvement of l-arginine-nitric oxide (NO) system in complex biological processes and numerous clinical conditions. Particular attention was made to reveal the association of l-arginine and methylarginines to outcome measures of women undergoing in vitro fertilization (IVF). This review attempts to summarize the expression and function of the essential elements of this system with particular reference to the different stages of female reproduction. A literature search was performed on the PubMed and Google Scholar systems. Publications were selected for evaluation according to the results presented in the Abstract. The regulatory role of NO during the period of folliculogenesis, oocyte maturation, fertilization, embryogenesis, implantation, placentation, pregnancy, and delivery was surveyed. The major aspects of cellular l-arginine uptake via cationic amino acid transporters (CATs), arginine catabolism by nitric oxide synthases (NOSs) to NO and l-citrulline and by arginase to ornithine, and polyamines are presented. The importance of NOS inhibition by methylated arginines and the redox-sensitive elements of the process of NO generation are also shown. The l-arginine-NO system plays a crucial role in all stages of female reproduction. Insufficiently low or excessively high rates of NO generation may have adverse influences on IVF outcome.
Topics: Pregnancy; Female; Humans; Nitric Oxide; Arginine; Nitric Oxide Synthase; Arginase; Ornithine
PubMed: 36499238
DOI: 10.3390/ijms232314908 -
Scientific Reports Sep 2020In vivo and vitro evidence indicates that ornithine and its related metabolic products play a role in tumor development. Whether ornithine is associated with breast...
In vivo and vitro evidence indicates that ornithine and its related metabolic products play a role in tumor development. Whether ornithine is associated with breast cancer in humans is still unclear. We examined the association between circulating ornithine levels and breast cancer in females. This 1:1 age-matched case-control study identified 735 female breast cancer cases and 735 female controls without breast cancer. All cases had a pathological test to ascertain a breast cancer diagnosis. The controls were ascertained using pathologic testing, clinical examinations, and/or other tests. Fasting blood samples were used to measure ornithine levels. The average age for cases and controls were 49.6 years (standard deviation [SD] 8.7 years) and 48.9 years (SD 8.7 years), respectively. Each SD increase in ornithine levels was associated with a 12% reduction of breast cancer risk (adjusted odds ratio [OR] 0.88; 95% confidence interval [CI] 0.79-0.97). The association between ornithine and breast cancer did not differ by pathological stages of diagnosis or tumor grades (all P for trend > 0.1). We observed no effect measure modification by molecular subtypes (P for interaction = 0.889). In conclusion, higher ornithine levels were associated with lower breast cancer risk in females.
Topics: Breast Neoplasms; Case-Control Studies; Female; Humans; Middle Aged; Odds Ratio; Ornithine; Risk Factors
PubMed: 32968187
DOI: 10.1038/s41598-020-72699-9 -
Cells May 2023The metabolism of the model microalgae under nitrogen deprivation is of special interest due to its resulting increment of triacylglycerols (TAGs), that can be applied... (Review)
Review
The metabolism of the model microalgae under nitrogen deprivation is of special interest due to its resulting increment of triacylglycerols (TAGs), that can be applied in biotechnological applications. However, this same condition impairs cell growth, which may limit the microalgae's large applications. Several studies have identified significant physiological and molecular changes that occur during the transition from an abundant to a low or absent nitrogen supply, explaining in detail the differences in the proteome, metabolome and transcriptome of the cells that may be responsible for and responsive to this condition. However, there are still some intriguing questions that reside in the core of the regulation of these cellular responses that make this process even more interesting and complex. In this scenario, we reviewed the main metabolic pathways that are involved in the response, mining and exploring, through a reanalysis of omics data from previously published datasets, the commonalities among the responses and unraveling unexplained or non-explored mechanisms of the possible regulatory aspects of the response. Proteomics, metabolomics and transcriptomics data were reanalysed using a common strategy, and an in silico gene promoter motif analysis was performed. Together, these results identified and suggested a strong association between the metabolism of amino acids, especially arginine, glutamate and ornithine pathways to the production of TAGs, via the de novo synthesis of lipids. Furthermore, our analysis and data mining indicate that signalling cascades orchestrated with the indirect participation of phosphorylation, nitrosylation and peroxidation events may be essential to the process. The amino acid pathways and the amount of arginine and ornithine available in the cells, at least transiently during nitrogen deprivation, may be in the core of the post-transcriptional, metabolic regulation of this complex phenomenon. Their further exploration is important to the discovery of novel advances in the understanding of microalgae lipids' production.
Topics: Chlamydomonas reinhardtii; Arginine; Nitrogen; Amino Acids; Triglycerides; Fasting; Ornithine
PubMed: 37408213
DOI: 10.3390/cells12101379 -
MSystems Aug 2022Fusobacterium nucleatum is a common constituent of the oral microbiota in both periodontal health and disease. Previously, we discovered ornithine cross-feeding between...
Fusobacterium nucleatum is a common constituent of the oral microbiota in both periodontal health and disease. Previously, we discovered ornithine cross-feeding between F. nucleatum and Streptococcus gordonii, where S. gordonii secretes ornithine via an arginine-ornithine antiporter (ArcD), which in turn supports the growth and biofilm development of F. nucleatum; however, broader metabolic aspects of F. nucleatum within polymicrobial communities and their impact on periodontal pathogenesis have not been addressed. Here, we show that when cocultured with S. gordonii, F. nucleatum increased amino acid availability to enhance the production of butyrate and putrescine, a polyamine produced by ornithine decarboxylation. Coculture with Veillonella parvula, another common inhabitant of the oral microbiota, also increased lysine availability, promoting cadaverine production by F. nucleatum. We confirmed that ArcD-dependent S. gordonii-excreted ornithine induces synergistic putrescine production, and mass spectrometry imaging revealed that this metabolic capability creates a putrescine-rich microenvironment on the surface of F. nucleatum biofilms. We further demonstrated that polyamines caused significant changes in the biofilm phenotype of a periodontal pathogen, Porphyromonas gingivalis, with putrescine accelerating the biofilm life cycle of maturation and dispersal. This phenomenon was also observed with putrescine derived from S. gordonii-F. nucleatum coculture. Lastly, analysis of plaque samples revealed cooccurrence of P. gingivalis with genetic modules for putrescine production by S. gordonii and F. nucleatum. Overall, our results highlight the ability of F. nucleatum to induce synergistic polyamine production within multispecies consortia and provide insight into how the trophic web in oral biofilm ecosystems can eventually shape disease-associated communities. Periodontitis is caused by a pathogenic shift in subgingival biofilm ecosystems, which is accompanied by alterations in microbiome composition and function, including changes in the metabolic activity of the biofilm, which comprises multiple commensals and pathogens. While Fusobacterium nucleatum is a common constituent of the supra- and subgingival biofilms, its metabolic integration within polymicrobial communities and the impact on periodontal pathogenesis are poorly understood. Here, we report that amino acids supplied by other commensal bacteria induce polyamine production by F. nucleatum, creating polyamine-rich microenvironments. Polyamines reportedly have diverse functions in bacterial physiology and possible involvement in periodontal pathogenesis. We show that the F. nucleatum-integrated trophic network yielding putrescine from arginine through ornithine accelerates the biofilm life cycle of Porphyromonas gingivalis, a periodontal pathogen, from the planktonic state through biofilm formation to dispersal. This work provides insight into how cooperative metabolism within oral biofilms can tip the balance toward periodontitis.
Topics: Humans; Fusobacterium nucleatum; Putrescine; Biofilms; Periodontitis; Porphyromonas gingivalis; Microbiota; Arginine; Ornithine
PubMed: 35852319
DOI: 10.1128/msystems.00170-22 -
Metabolites Dec 2022Along the maternal-fetal-neonatal axis, one of the problems relating to the maternal-neonatal axis is infant sleep problems including nighttime crying. One possible...
Along the maternal-fetal-neonatal axis, one of the problems relating to the maternal-neonatal axis is infant sleep problems including nighttime crying. One possible solution could be to provide the newborn with sleep-promoting ingredients through breast milk or formula. So far, it has been reported that L-ornithine has a sleep-related effect. Therefore, we investigated the effect of dietary L-ornithine on maternal mouse plasma and milk L-ornithine levels in Experiment 1. In Experiment 2, a single dose of L-ornithine was applied to know the time-course changes in plasma, mammary gland and milk L-ornithine levels. Experiment 3 was conducted to confirm sleep behavior as well as changes in polyamine levels in milk. L-Ornithine levels in maternal plasma significantly increased by both dietary regimen and single oral administration in Experiments 1 and 2. Both L-ornithine treatments also increased its levels in milk, although not to a concentration as high as in plasma. In Experiment 3, the level of polyamines, which are metabolized from L-ornithine, did not significantly differ after L-ornithine administration. In sleep-like behavior observations, the average concentration of L-ornithine in milk did not increase the sleep-like behavior of mouse pups. However, more concentrated L-ornithine solutions can significantly increase sleep-like behavior. These results revealed that even if mothers ingested L-ornithine to increase L-ornithine levels in breast milk, it is difficult to promote sleep in newborns. Because it is difficult to raise L-ornithine in breast milk to sleep-inducing levels, L-ornithine added formula may partially improve infant sleep and has the potential for preventing infant sleep problems such as nighttime crying.
PubMed: 36557279
DOI: 10.3390/metabo12121241 -
Cell Death & Disease Sep 2023The enzyme arginase 1 (A1) hydrolyzes the amino acid arginine to form L-ornithine and urea. Ornithine is further converted to polyamines by the ornithine decarboxylase...
The enzyme arginase 1 (A1) hydrolyzes the amino acid arginine to form L-ornithine and urea. Ornithine is further converted to polyamines by the ornithine decarboxylase (ODC) enzyme. We previously reported that deletion of myeloid A1 in mice exacerbates retinal damage after ischemia/reperfusion (IR) injury. Furthermore, treatment with A1 protects against retinal IR injury in wild-type mice. PEG-A1 also mitigates the exaggerated inflammatory response of A1 knockout (KO) macrophages in vitro. Here, we sought to identify the anti-inflammatory pathway that confers macrophage A1-mediated protection against retinal IR injury. Acute elevation of intraocular pressure was used to induce retinal IR injury in mice. A multiplex cytokine assay revealed a marked increase in the inflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the retina at day 5 after IR injury. In vitro, blocking the A1/ODC pathway augmented IL-1β and TNF-α production in stimulated macrophages. Furthermore, A1 treatment attenuated the stimulated macrophage metabolic switch to a pro-inflammatory glycolytic phenotype, whereas A1 deletion had the opposite effect. Screening for histone deacetylases (HDACs) which play a role in macrophage inflammatory response showed that A1 deletion or ODC inhibition increased the expression of HDAC3. We further showed the involvement of HDAC3 in the upregulation of TNF-α but not IL-1β in stimulated macrophages deficient in the A1/ODC pathway. Investigating HDAC3 KO macrophages showed a reduced inflammatory response and a less glycolytic phenotype upon stimulation. In vivo, HDAC3 co-localized with microglia/macrophages at day 2 after IR in WT retinas and was further increased in A1-deficient retinas. Collectively, our data provide initial evidence that A1 exerts its anti-inflammatory effect in macrophages via ODC-mediated suppression of HDAC3 and IL-1β. Collectively we propose that interventions that augment the A1/ODC pathway and inhibit HDAC3 may confer therapeutic benefits for the treatment of retinal ischemic diseases.
Topics: Animals; Mice; Arginase; Cytokines; Ischemia; Myeloid Cells; Ornithine; Ornithine Decarboxylase; Reperfusion Injury; Retinal Diseases; Tumor Necrosis Factor-alpha
PubMed: 37735154
DOI: 10.1038/s41419-023-06147-7 -
International Journal of Medical... 2021Neutrophil extracellular traps (NETs) have been implicated in host immune responses. Attempts have been made to examine how NETs affect the pathogenesis of...
Neutrophil extracellular traps (NETs) have been implicated in host immune responses. Attempts have been made to examine how NETs affect the pathogenesis of complications such as autoimmune and vascular disorders. This study aimed to explore the relationship between NETs and vasculitis. The current study entailed the searching of PsycINFO, PubMed, Web of Science, and CINAHL for articles related to the research topic. The search terms and phrases included "vasculitis," "NETs," "neutrophil extracellular traps," "NETosis," and "pathogenesis." The search was limited to articles published between 2009 and 2019. Researchers have shown that NETs contribute to the pathogenesis of vasculitis through different mechanisms and processes, including renal failure and vascular damage. The protective effects of NETs have also been highlighted. Overall, some scholars have shown the effectiveness of using DNase I and the PAD4 inhibitor Cl-amidine to treat vasculitis by restricting NET formation. However, observations have been noted in only animal experimental models. Neutrophil hyperactivity and its role in vasculitis are not yet fully understood. More studies aiming to determine the accurate function of NETs in vasculitis pathogenesis, particularly in humans, should be undertaken. Intensive research on NETs and vasculitis can increase the knowledge of medical practitioners and contribute to the development of new treatment methods to enhance patient outcomes in the future.
Topics: Animals; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Apoptosis; Deoxyribonuclease I; Disease Models, Animal; Extracellular Traps; Giant Cell Arteritis; Humans; Neutrophils; Ornithine; Protein-Arginine Deiminase Type 4; Regulated Cell Death; Takayasu Arteritis
PubMed: 33746569
DOI: 10.7150/ijms.53728 -
The Journal of Biological Chemistry Jul 2023The Gram-positive bacterium Bacillus subtilis can utilize several proteinogenic and non-proteinogenic amino acids as sources of carbon, nitrogen, and energy. The...
The Gram-positive bacterium Bacillus subtilis can utilize several proteinogenic and non-proteinogenic amino acids as sources of carbon, nitrogen, and energy. The utilization of the amino acids arginine, citrulline, and ornithine is catalyzed by enzymes encoded in the rocABC and rocDEF operons and by the rocG gene. The expression of these genes is controlled by the alternative sigma factor SigL. RNA polymerase associated with this sigma factor depends on ATP-hydrolyzing transcription activators to initiate transcription. The RocR protein acts as a transcription activator for the roc genes. However, the details of amino acid metabolism via this pathway are unknown. Here, we investigated the contributions of all enzymes of the Roc pathway to the degradation of arginine, citrulline, and ornithine. We identified the previously uncharacterized RocB protein as responsible for the conversion of citrulline to ornithine. In vitro assays with the purified enzyme suggest that RocB acts as a manganese-dependent N-carbamoyl-L-ornithine hydrolase that cleaves citrulline to form ornithine and carbamate. Moreover, the molecular effector that triggers transcription activation by RocR has not been unequivocally identified. Using a combination of transcription reporter assays and biochemical experiments, we demonstrate that ornithine is the molecular inducer of RocR activity. Taken together, our work suggests that binding of ATP to RocR triggers its hexamerization, and binding of ornithine then allows ATP hydrolysis and activation of roc gene transcription. Thus, ornithine is the central molecule of the roc degradative pathway as it is the common intermediate of arginine and citrulline degradation and the molecular effector of RocR.
Topics: Adenosine Triphosphate; Arginine; Bacillus subtilis; Bacterial Proteins; Citrulline; Ornithine; Sigma Factor; Transcription Factors
PubMed: 37343703
DOI: 10.1016/j.jbc.2023.104944 -
BMJ Case Reports May 2015A 54-year-old woman with coeliac disease was admitted to hospital electively for supplemental nutrition. Shortly after feeding started she deteriorated into a...
A 54-year-old woman with coeliac disease was admitted to hospital electively for supplemental nutrition. Shortly after feeding started she deteriorated into a hyperammonemic coma with refeeding syndrome, requiring an extensive intensive care admission. Urea cycle disorders were investigated and a biochemical diagnosis of ornithine transcarbamylase deficiency was made. This is a rare diagnosis in the adult population. This case report summarises protein metabolism, urea cycle disorders and the challenges of management.
Topics: Coma; Diagnosis, Differential; Female; Humans; Hyperammonemia; Middle Aged; Ornithine Carbamoyltransferase Deficiency Disease
PubMed: 25948840
DOI: 10.1136/bcr-2014-205592