Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.1.17 (ornithine decarboxylase)
6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the properties of mammalian arginine decarboxylase (ADC) and ornithine decarboxylase (ODC) in rat liver and brain. Mammalian ADC is thermally unstable and associated with mitochondrial membranes. ADC decarboxylates both arginine (Km = 0.75 mM) and ornithine (Km = 0.25 mM), a reaction not inhibited by the specific ODC inhibitor, difluoromethylomithine. ADC activity is inhibited by Ca2+, Co2+, and polyamines, is present in many organs being highest in aorta and lowest in testis, and is not recognized by a specific monoclonal antibody to ODC. In contrast, ODC is thermally stable, cytosolic, and mitochondrial and is expressed at low levels in most organs except testis. Although ADC and ODC are expressed in cultured rat C6 glioma cells, the patterns of expression during growth and confluence are very different. We conclude that mammalian ADC differs from ADC isoforms expressed in plants, bacteria, or Caenorhabditis elegans and is distinct from ODC. ADC serves to synthesize agmatine in proximity to mitochondria, an organelle also harboring agmatine's degradative enzyme, agmatinase, and a class of imidazoline receptor (I2) to which agmatine binds with high affinity.
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PMID:Characterization of arginine decarboxylase in rat brain and liver: distinction from ornithine decarboxylase. 1080 Sep 66

Agmatinase, which hydrolyzes agmatine to putrescine and urea, not only represents a potentially important mechanism for regulating the biological effects of agmatine in mammalian cells but also represents an alternative to ornithine decarboxylase for polyamine biosynthesis. We have isolated a full-length cDNA encoding human agmatinase whose function was confirmed by complementation in yeast. The single-copy human agmatinase gene located on chromosome 1 encodes a 352-residue protein with a putative mitochondrial targeting sequence at the NH(3)-terminus. Human agmatinase has about 30% identity to bacterial agmatinases and <20% identity to mammalian arginases. Residues required for binding of Mn(2+) at the active site in bacterial agmatinase and other members of the arginase superfamily are fully conserved in human agmatinase. Agmatinase mRNA is most abundant in human liver and kidney but also is expressed in several other tissues, including skeletal muscle and brain. Its expression in human liver is induced during hepatitis B virus infection, suggesting that agmatinase may play a role in the pathophysiology of this disease.
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PMID:Cloning of human agmatinase. An alternate path for polyamine synthesis induced in liver by hepatitis B virus. 1180 60

Putrescine is the immediate precursor for the synthesis of polyamines and is normally generated by the action of ornithine decarboxylase. However, putrescine can also be produced by the conversion of arginine to agmatine by arginine decarboxylase (bADC) followed by the release of urea by agmatine ureohydrolase. Amino-acid sequence homology with the eukaryotic ornithine decarboxylases suggests that bADC may be a model for this group of decarboxylases. We report here the crystallization of arginine decarboxylase from E. coli. Crystals up to 1 mm in size are grown by vapor equilibration using Li(2)SO(4) and polyethylene glycols as precipitants. The crystals exhibit diffraction maxima beyond 3 A resolution and belong to space group P4(1(3))2(1)2 with a = 192.4 and c = 121.0 A. These unit-cell dimensions together with the estimated density of the crystals suggest the presence of one tetramer of bADC (71 kDa subunit(-1)) per asymmetric unit (V(m) = 2.0 A(3) Da(-1)).
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PMID:Crystallization of biosynthetic arginine decarboxylase from Escherichia coli. 1529 55

Arginine decarboxylase (ADC) is the first enzyme in the alternative route to putrescine in the polyamine biosynthesis pathway in bacteria and plants. In this study, we have focused on the effects of various types of short-term stresses on the transcript amount and specific activity of Synechocystis sp. PCC 6803 ADC. Our results reveal that the steady-state transcript accumulation and enzyme activity are not connected in a simple manner, since only photoheterotrophy and synergistic salt and high-light stress affected both parameters similarly. Changes in the steady-state ADC mRNA accumulation under the other short-term stress conditions studied had only a small impact on enzyme activity, suggesting post-translational regulation. Based on structural modeling, Synechocystis ADCs have a putative extra domain, which might be involved in the post-translational regulation of ADC activity in Synechocystis. In addition, two symmetric inter-subunit disulfide bonds seem to stabilize the dimeric structure of ADCs. There are two genes coding for ADC and agmatinase, another polyamine pathway enzyme, in Synechocystis genome, while the genes coding for ornithine decarboxylase and for some other enzymes in the polyamine pathway were not identified with homology searches.
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PMID:Structural modeling and environmental regulation of arginine decarboxylase in Synechocystis sp. PCC 6803. 1636 87

Agmatine is an endogenous neuromodulator that, based on animal studies, has the potential for new drug development. As an endogenous aminoguanidine compound (1-amino-4-guanidinobutane), it is structurally unique compared with other monoamines. Agmatine was long thought to be synthesised only in lower life forms, until its biosynthetic pathway (decarboxylation of arginine) was described in the mammalian brain in 1994. Human arginine decarboxylase has been cloned and shown to have 48% identity to ornithine decarboxylase. In neurons of the brain and spinal cord, agmatine is packaged into synaptic vesicles and released upon neuronal depolarisation. Other evidence of a neuromodulation role for agmatine is the presence of a specific cellular uptake mechanism and a specific metabolic enzyme (agmatinase; which forms putrescine).Initially, agmatine was conceptualised as an endogenous clonidine-displacing substance of imidazoline receptors; however, it has now been established to have affinity for several transmembrane receptors, such as alpha(2)-adrenergic, imidazoline I(1) and glutamatergic NMDA receptors. In addition to activity at these receptors, agmatine irreversibly inhibits neuronal nitric oxide synthase and downregulates inducible nitric oxide synthase. Endogenous agmatine is induced in response to stress and/or inflammation. Stressful conditions that induce agmatine include hypoxic-ischaemia and cold-restraint stress of ulcerogenic proportion. Induction of agmatine in the brain seems to occur in astrocytes, although neurons also synthesise agmatine. The effects of injected agmatine in animals include anticonvulsant-, antineurotoxic- and antidepressant-like actions. Intraperitoneal or intracerebroventricular injections of agmatine rapidly elicit antidepressant-like behavioural changes in the rodent forced swim test and tail suspension test. Intraperitoneal injections of agmatine into rats and mice also elicit acute anxiolytic-like behavioural changes in the elevated plus-maze stress test. In an animal model of acute stress disorder, intraperitoneal agmatine injections diminish contextual fear learning. Furthermore, intraperitoneal injections of agmatine reduce alcohol and opioid dependence by diminishing behaviour in a rat conditioned place preference paradigm. Based on these findings, agmatine appears to be an endogenous neuromodulator of mental stress. The possible roles and/or beneficial effects of agmatine in stress-related disorders, such as depression, anxiety and post-traumatic stress disorder, merit further investigation.
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PMID:Agmatine : metabolic pathway and spectrum of activity in brain. 1792 94

Regulation of agmatine homeostasis has so far only been poorly defined. In the present study, three mechanisms regulating human agmatine homeostasis were investigated. 1) Enzymatic regulation: expression of arginine decarboxylase, diamine oxidase, and ornithine decarboxylase in human colon neoplastic tissue was, at the mRNA level, about 75% and 50% lower and 150% higher, respectively, than in the adjacent normal tissue; expression of agmatinase was unchanged. 2) Bacteria-derived agmatine: ten representative bacteria strains of the human intestinal microbiota considerably differed in agmatine production and its efflux into their surrounding fluid, suggesting that the composition of the intestinal microbiota influences the agmatine availability in the gut lumen for absorption. 3) Regulation of blood plasma agmatine concentration by the human liver: at low concentrations in portal venous blood plasma, agmatine either slightly increased or further decreased in blood plasma through liver passage. Above a threshold of 14 ng/ml agmatine in the portal venous blood plasma, substantial hepatic agmatine removal from blood occurred. Taken together, a perturbation of agmatine homeostasis has been proven to be involved in the regulation of malignant cell proliferation. The amount of agmatine available for absorption, which is an important physiological source of agmatine in the human organism, should differ considerably depending on the composition of the bacterial flora in the chyme since the various species of intestinal bacteria largely differ in their ability to form agmatine. Finally, evidence has been presented that the liver plays a crucial physiological role in the maintenance of agmatine homeostasis in the human organism.
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PMID:Regulatory mechanisms underlying agmatine homeostasis in humans. 1883 51

l-Arginine metabolism by the arginase and nitric oxide (NO) synthase (NOS) families of enzymes is important in NO production, and imbalances between these pathways contribute to airway hyperresponsiveness (AHR) in asthma. To investigate the role of arginase isozymes (ARG1 and ARG2) in AHR, we determined the protein expression of ARG1, ARG2, the NOS isozymes, and other proteins involved in l-arginine metabolism in lung tissues from asthma patients and in acute (3-wk) and chronic (12-wk) murine models of ovalbumin-induced airway inflammation. Expression of ARG1 was increased in human asthma, whereas ARG2, NOS isoforms, and the other l-arginine-related proteins (i.e., cationic amino acid transporters 1 and 2, agmatinase, and ornithine decarboxylase) were unchanged. In the acute murine model of allergic airway inflammation, augmentation of ARG1 expression was similarly the most dramatic change in protein expression. However, ARG2, NOS1, NOS2, and agmatinase were also increased, whereas NOS3 expression was decreased. Arginase inhibition in vivo with nebulized S-(2-boronoethyl)-l-cysteine attenuated the methacholine responsiveness of the central airways in mice from the acute model. Further investigations in the chronic murine model revealed an expression profile that more closely paralleled the human asthma samples: only ARG1 expression was significantly increased. Interestingly, in the chronic mouse model, which generates a remodeling phenotype, arginase inhibition attenuated methacholine responsiveness of the central and peripheral airways. The similarity in arginase expression between human asthma and the chronic model and the attenuation of AHR after in vivo treatment with an arginase inhibitor suggest the potential for therapeutic modification of arginase activity in asthma.
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PMID:Functionally important role for arginase 1 in the airway hyperresponsiveness of asthma. 1928 31

A strain of Escherichia coli was constructed in which all of the genes involved in polyamine biosynthesis--speA (arginine decarboxylase), speB (agmatine ureohydrolase), speC (ornithine decarboxylase), spe D (adenosylmethionine decarboxylase), speE (spermidine synthase), speF (inducible ornithine decarboxylase), cadA (lysine decarboxylase), and ldcC (lysine decarboxylase)--had been deleted. Despite the complete absence of all of the polyamines, the strain grew indefinitely in air in amine-free medium, albeit at a slightly (ca. 40 to 50%) reduced growth rate. Even though this strain grew well in the absence of the amines in air, it was still sensitive to oxygen stress in the absence of added spermidine. In contrast to the ability to grow in air in the absence of polyamines, this strain, surprisingly, showed a requirement for polyamines for growth under strictly anaerobic conditions.
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PMID:Polyamines are not required for aerobic growth of Escherichia coli: preparation of a strain with deletions in all of the genes for polyamine biosynthesis. 1954 71

Recent findings demonstrated the dysregulation of imidazoline receptor binding sites in major depression and their normalization by chronic treatment with antidepressants including selective serotonin reuptake inhibitors (SSRIs). Present study investigated the role of agmatine and imidazoline receptors in antidepressant like effect of SSRIs and imipramine in mouse forced swimming test (FST) paradigm. The antidepressant like effect of fluoxetine or paroxetine was potentiated by imidazoline I(1)/I(2) receptor agonist agmatine (5-10 mg/kg, ip), imidazoline I(1) receptor agonists, moxonidine (0.25-0.5 mg/kg, ip) and clonidine (0.015-0.03 mg/kg, ip), imidazoline I(2) receptor agonist, 2-(2-benzofuranyl)-2-imidazoline (5-10 mg/kg, ip) as well as by the drugs known to increase endogenous agmatine levels in brain viz., L-arginine, an agmatine biosynthetic precursor (40 microg/mouse, icv), ornithine decarboxylase inhibitor, difluoromethyl ornithine (12.5 microg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5 microg/mouse, icv) and agmatinase inhibitor, arcaine (50 microg/mouse, icv). Conversely, prior administration of I(1) receptor antagonist, efaroxan (1 mg/kg, ip), I(2) receptor antagonist, idazoxan (0.25 mg/kg, ip) and arginine decarboxylase inhibitor, d-arginine (100 mg/kg, ip) blocked the antidepressant like effect of paroxetine (10 mg/kg, ip) and fluoxetine (20 mg/kg, ip). On the other hand, antidepressant like effect of imipramine was neither augmented nor attenuated by any of the above drugs. Mice pretreated with SSRIs but not imipramine and exposed to FST showed higher concentration of agmatine in brain as compared to saline control. This effect of SSRIs on agmatine levels was completely blocked by arginine decarboxylase inhibitor d-arginine but not by imidazoline receptor antagonists, efaroxan or idazoxan. These results demonstrate that modulation of imidazoline receptors by agmatine are implicated in the antidepressant like effect of SSRIs and may be projected as a potential therapeutic target for the treatment of depressive disorders.
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PMID:Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine. 1958 48

Present study investigated the role of agmatine in ethanol-induced anxiolysis and withdrawal anxiety using elevated plus maze (EPM) test in rats. The anxiolytic-like effect of ethanol was potentiated by pretreatment with imidazoline I(1)/I(2) receptor agonist agmatine (10-20 mg/kg, i.p.), imidazoline I(1) receptor agonists, moxonidine (0.25 mg/kg, i.p.) and clonidine (0.015 mg/kg, i.p.), imidazoline I(2) receptor agonist, 2-BFI (5 mg/kg, i.p.) as well as by the drugs known to increase endogenous agmatine levels in brain viz., L-arginine, an agmatine biosynthetic precursor (100 microg/rat, i.c.v.), ornithine decarboxylase inhibitor, DFMO (125 microg/rat, i.c.v.), diamine oxidase inhibitor, aminoguanidine (65 microg/rat, i.c.v.) and agmatinase inhibitor, arcaine (50 microg/rat, i.c.v.). Conversely, prior administration of I(1) receptor antagonist, efaroxan (1 mg/kg, i.p.), I(2) receptor antagonist, idazoxan (0.25mg/kg, i.p.) and arginine decarboxylase inhibitor, D-arginine (100 microg/rat, i.c.v.) blocked the anxiolytic-like effect of ethanol. Moreover, ethanol withdrawal anxiety was markedly attenuated by agmatine (10-20 mg/kg, i.p.), moxonidine (0.25 mg/kg, i.p.), clonidine (0.015 mg/kg, i.p.), 2-BFI (5 mg/kg, i.p.), L-arginine (100 microg/rat, i.c.v.), DFMO (125 microg/rat, i.c.v.), aminoguanidine (65 microg/rat, i.c.v.) and arcaine (50 microg/rat, i.c.v.). The anti-anxiety effect of agmatine in ethanol-withdrawn rats was completely blocked by efaroxan (1 mg/kg, i.p.) and idazoxan (0.25 mg/kg, i.p.). These results suggest that agmatine and imidazoline receptor system may be implicated in ethanol-induced anxiolysis and withdrawal anxiety and strongly support further investigation of agmatine in ethanol dependence mechanism. The data also project agmatine as a potential therapeutic target in overcoming alcohol withdrawal symptoms such as anxiety.
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PMID:Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. 2039 43


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