Role of Polyamines in Prolactin Actions
James A. Rillema in Actions of Prolactin on Molecular Processes, 1987
Polyamine biosynthesis in eukaryotic cells involves several precursors such as arginine, ornithine, methionine, and S-adenosylmethionine (Figure 2). Ornithine is mainly formed in the urea cycle through the cleavage of urea from arginine by arginase. Ornithine is then converted to putrescine in a reaction catalyzed by ornithine decarboxylase (ODC).29–31S-Adenosylmethionine is a universal methyl donor in transmethylation reactions. In polyamine biosynthesis, this compound is first decarboxylated by S-adenosylmethionine decarboxylase (S-ado-met DC).29–31S-Ado-met serves as the propylamine donor in the formation of spermidine from putrescine by spermidine synthase as well as in the formation of spermine from spermidine by spermine synthase.29–31
Argininemia
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
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
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
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.
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.
Comprehensive analysis of metabolic changes in spontaneously hypertensive rats
Published in Clinical and Experimental Hypertension, 2023
Yanan Li, Dadi Xie, Luxi Li, Pei Jiang
Significant changes in arginine synthesis and metabolism were also detected in multiple tissues. The effects of arginine on hypertension are multifaceted. Arginine can be metabolized into various products, including NO, urea, creatine, proline, and glutamate, which affect the development of hypertension in different ways. The arginine-NO pathway plays a vital role in maintaining vascular homeostasis. NO can diffuse into vascular smooth muscle cells through the guanylate cyclase pathway, causing vasodilation (26). Studies have shown that inhibition of NO synthesis exacerbates the development of hypertension (27). In contrast, increased NO bioavailability leads to antihypertensive effects and improves target organ damage in hypertension (28). In addition, the arginine and proline metabolic pathways also exhibited abnormalities. Proline is a specific secondary amino acid that can be interconverted with glutamate. Glutamate can generate glutamic-γ-semialdehyde and be converted to ornithine, a precursor for arginine synthesis in the urea cycle (29). On the other hand, glutamic-γ-semialdehyde produces pyrroline-5-carboxylate and converts it to proline. Studies have shown that arginase can convert arginine into ornithine and urea. Increased expression of arginase can reduce NO synthesis and promote glutamate and proline production (30). Disorders of arginine biosynthesis and arginine and proline metabolism found in multiple tissues of 5-week-old SHR may affect endothelial function by decreasing NO bioactivity, which may be another critical pathway in the regulation of hypertension.
Complement inhibitor factor H expressed by breast cancer cells differentiates CD14+ human monocytes into immunosuppressive macrophages
Published in OncoImmunology, 2020
Karolina I. Smolag, Christine M. Mueni, Karin Leandersson, Karin Jirström, Catharina Hagerling, Matthias Mörgelin, Paul N. Barlow, Myriam Martin, Anna M. Blom
Many other altered genes are associated with macrophage activation and polarization.42-46 Among these, numerous M2-related genes were upregulated. Changes in tryptophan and arginine metabolism also suggest that FH promotes an immunosuppressive phenotype. Upregulation of tryptophan metabolism impairs T-cell proliferation. Consequently, the ability of T-cells to kill pathogens and cancer cells is inhibited.47 Arginine depletion also affects T-cells in a similar way, which is well documented in in vivo studies.48 In man, many reports document arginase activity in monocytes and macrophages, while others do not. One of the reasons for this controversy might be the usage of different models and detection methods, with measurement of arginase activity being much more sensitive than direct detection of arginase expression.49 In our experimental setup, human macrophages stimulated with M2 stimuli as well as with FH showed relatively high arginase activity.