China
Africa
Explore chapters and articles related to this topic
Argininemia
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The molecular defect is in the enzyme arginase 1. It catalyzes the conversion of arginine to urea and ornithine (see Figure 30.1). Arginase 1, encoded by ARG1 and referred to as the liver isoform, contributes 98 percent of the arginase activity in liver but is also present in red cells. The mitochondrial isoform arginase 2, which predominates in the kidney [28], is encoded by a separate gene loci ARG2 at 14q24.1. Arginase 2 activity becomes elevated in patients with argininemia [29], and it appears possible that the presence of arginase 2 in argininemia provides some degree of protection from nitrogen accumulation, resulting in less severe hyperammonemic episodes than in other urea cycle disorders. The activity of the renal arginase also provides the mechanism for the relatively normal production of urea in these patients. The renal enzyme is 58 percent identical to the hepatic enzyme and 70 percent identical to Xenopus arginase.
Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Hyperlysinemia probably contains more than one disease form. In this condition, normal or high protein intake brings about increased lysine levels in cerebrospinal fluid and plasma. Ammonia and arginine are also raised. On the other hand, the urinary amino acid excretion is normal. Low lysine containing diets prevent the changes from the normal amino acid pattern. The enzymes of the urea cycle are present, however, lysine metabolism is impaired and the increased lysine is a potent inhibitor of arginase. The inhibition of arginase activity affects the urea cycle and decreases detoxication by ammonia. In hyperlysinemia, defects exist in the incorporation of lysine into proteins, because the clinical symptoms of seizures and the appearance of weakness of the muscles and anemia in patients are similar to the actions of lysine deficient diets.
Enzymatic Amino Acid Deprivation Therapies Targeting Cancer
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Carla S. S. Teixeira, Henrique S. Fernandes, Sérgio F. Sousa, Nuno M. F. S. A. Cerqueira
In the meanwhile, new strategies to improve arginase potential have arouse and at the moment there is a completed clinical trial (NCT01092091) were it was shown that rhArgI-PEG has a manageable safety profile and is potentially a superior arginine depleting agent than ADI in the treatment of HCC. At the moment there are about 10 clinical trials in different stages evaluating the effectiveness and safety of arginase as a potential anti-cancer therapeutic targets. The combination of the different arginine depleting enzymes with existing therapy is also being tested. The observation that patients submitted to prolonged arginine depletion showed a relative superior overall survival is a valid reason to keep the exploitation of arginine deprivation as a potential therapy against some cancers.
Drugs and nanoformulations for the management of Leishmania infection: a patent and literature review (2015-2022)
Published in Expert Opinion on Therapeutic Patents, 2023
Mariana Verdan, Igor Taveira, Flávia Lima, Fernanda Abreu, Dirlei Nico
Polyamines play a fundamental role in cell growth and differentiation. Arginine is an amino acid necessary for Leishmania and host metabolism [76]. Arginase is an enzyme responsible for the cleavage of arginine, producing ornithine and urea. In Leishmania, arginase is one of the relevant enzymes in the polyamine biosynthesis pathway, which is responsible for converting arginine into ornithine [77]. In the Leishmania glycosome, arginase is also involved in trypanothione biosynthesis. Da Silva and colleagues demonstrated fundamental arginase activity in L. amazonensis, confirming arginase as an essential molecular target [78]. This study showed that Leishmania mutants for arginase decreased the power of infection in vitro. By the way, any other critical metabolic marks are under investigation. We will not extend our discussion on this issue so as not to deviate from the topic.
Health care resource utilization in the management of patients with Arginase 1 Deficiency in the US: a retrospective, observational, claims database study
Published in Journal of Medical Economics, 2022
Aseel Bin Sawad, John Jackimiec, Mark Bechter, Michael Hull, Jason Yeaw, Yi Wang, George A. Diaz
In most cases, manifestations of ARG1-D first appear between the ages of 1 and 3 years. Diagnosis is based on elevated plasma arginine levels, reduced red blood cell arginase activity, or identification of ARG1 variants, after clinical suspicion1. However, delays in diagnosis or misdiagnosis are frequent for several reasons16. Likely due to its perceived rarity, disease awareness is lower for ARG1-D than other UCDs, which can result in delays in appropriate screening/work-up activities. Further, other more common neurological diseases such as cerebral palsy and hereditary spastic paraplegia, are similar to ARG1-D in initial clinical presentation and may lead to misdiagnosis and/or delayed ARG1-D diagnosis2,17. In areas where newborn screening is available, infants with ARG1-D can be identified in the first days of life1; however, there are limitations to these programs, including false-negative results, lack of universal availability, and an absence of standardized diagnostic thresholds18–20. The current challenges with diagnosis may prevent timely treatment initiation, which may contribute to the progression of the disease and lead to increasing health care resource utilization (HCRU) over time.
Sexual Dimorphism in Alternative Metabolic Pathways of L-Arginine in Circulating Leukocytes in Young People with Type 1 Diabetes Mellitus
Published in Endocrine Research, 2021
Nina Alchujyan, Margarita Hovhannisyan, Nina Movsesyan, Arthur Melkonyan, Vanuhi Shaboyan, Yelena Aghajanova, Grigory Minasyan, Guevork Kevorkian
Since arginase and NOS are present in various subpopulations of immune blood cells that are involved in the pathophysiology of T1DM, we aimed primarily to assess the overall picture of L-arginine metabolism in circulating leukocytes in T1DM. We found a sex- and age-dependent increase in arginase activity, accompanied mainly by a decrease in the production of bioavailable NO in the cytoplasm and mitochondria in the PBL of young people with T1DM. In adolescent children/girls with RO-T1DM, there was a greater activation of arginase compared to boys with a shift toward mARG activity, which provides the synthesis of proline and/or glutamate in mitochondria via ornithine aminotransferase, while cARG provides the synthesis of polyamines in cytoplasm via ornithine decarboxylase.9 Circulating polyamine levels are elevated in autoimmune diseases, and inhibition of their synthesis increases β-cell area and insulin secretion, improves blood glucose control, and also increases the number of Treg cells and reduces the number of potentially pathogenic Th17 cells in the pancreatic lymph nodes in T1DM.34 Arginase-induced increase in the production of polyamines and proline can lead to vascular cell proliferation and collagen formation with thickening, fibrosis, and stiffness of the blood vessels and airways, which underlie the cardiovascular complications and metabolic disorders in diabetes.35,36 In addition, excessive arginase activation can cause arginine deficiency, leading to dysfunction of immune cells and/or endothelial dysfunction in humans.8