scholarly journals A perspective of polyamine metabolism

2003 ◽  
Vol 376 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Heather M. WALLACE ◽  
Alison V. FRASER ◽  
Alun HUGHES
Keyword(s):  
Tumour Cells ◽  
Polyamine Metabolism ◽  
Parasitic Infections ◽  
Proof Of Concept ◽  
Compensatory Mechanisms ◽  
Polyamine Analogues ◽  
Cellular Effects ◽  
Current Thinking ◽  
Polyamine Content ◽  
And Function

Polyamines are essential for the growth and function of normal cells. They interact with various macromolecules, both electrostatically and covalently and, as a consequence, have a variety of cellular effects. The complexity of polyamine metabolism and the multitude of compensatory mechanisms that are invoked to maintain polyamine homoeostasis argue that these amines are critical to cell survival. The regulation of polyamine content within cells occurs at several levels, including transcription and translation. In addition, novel features such as the +1 frameshift required for antizyme production and the rapid turnover of several of the enzymes involved in the pathway make the regulation of polyamine metabolism a fascinating subject. The link between polyamine content and human disease is unequivocal, and significant success has been obtained in the treatment of a number of parasitic infections. Targeting the polyamine pathway as a means of treating cancer has met with limited success, although the development of drugs such as DFMO (α-difluoromethylornithine), a rationally designed anticancer agent, has revolutionized our understanding of polyamine function in cell growth and provided ‘proof of concept’ that influencing polyamine metabolism and content within tumour cells will prevent tumour growth. The more recent development of the polyamine analogues has been pivotal in advancing our understanding of the necessity to deplete all three polyamines to induce apoptosis in tumour cells. The current thinking is that the polyamine inhibitors/analogues may also be useful agents in the chemoprevention of cancer and, in this area, we may yet see a revival of DFMO. The future will be in adopting a functional genomics approach to identifying polyamine-regulated genes linked to either carcinogenesis or apoptosis.

Polyamine metabolism and function

1982 ◽  
Vol 243 (5) ◽  
pp. C212-C221 ◽  
Author(s):  
A. E. Pegg ◽  
P. P. McCann
Keyword(s):  
Molecular Weight ◽  
Tissue Growth ◽  
Polyamine Metabolism ◽  
Organic Cations ◽  
Low Molecular Weight ◽  
Polyamine Biosynthesis ◽  
Polyamine Content ◽  
And Function ◽  
Specific Inhibitors

Polyamines are ubiquitous organic cations of low molecular weight. The content of these amines is closely regulated by the cell according to the state of growth. The reactions responsible for the biosynthesis and interconversion of the polyamines and their precursor putrescine are described and the means by which polyamine content can be varied in response to exogenous stimuli are discussed. The role of polyamines in the cell cycle, cell division, tissue growth, and differentiation is considered. Recent studies using highly specific inhibitors of polyamine biosynthesis such as alpha-difluoromethylornithine to prevent accumulation of polyamines have indicated that the synthesis of polyamines is intimately associated with these processes. Such inhibitors have great potential for investigation of the cellular role of polyamines.

Polyamine metabolism in the Microsporidia

2003 ◽  
Vol 31 (2) ◽  
pp. 420-423 ◽  
Author(s):  
C.J. Bacchi ◽  
N. Yarlett ◽  
L.M. Weiss
Keyword(s):  
Metabolic Pathways ◽  
Tumour Cells ◽  
Polyamine Metabolism ◽  
Immunocompromised Patients ◽  
Obligate Intracellular ◽  
Polyamine Analogues ◽  
Intracellular Parasites ◽  
Recent Developments ◽  
Polyamine Uptake ◽  
Block Growth

Members of the phylum Microspora are all obligate intracellular parasites. Little is known concerning metabolic pathways in these parasites, some of which pose serious problems in immunocompromised patients. We investigated polyamine metabolism in the systemic pathogen Enterocytozoon cuniculi using intact pre-emergent spores, and cell-free preparations. We found both polyamine synthetic and interconversion pathways to be operative, as evidenced by conversion of ornithine into polyamines, and production of spermidine from spermine by pre-emergent spores. Recent developments in the antitumour field have highlighted the ability of bis-ethylated polyamine analogues to reduce polyamine levels and block growth of tumour cells. In light of enhanced polyamine uptake in Enc. cuniculi, we have begun to study bis-aryl 3-7-3 and bis-ethyl oligoamine analogues as leads for chemotherapy of microsporidia.

scholarly journals Spermidine/spermine-N1-acetyltransferase-2 (SSAT2) acetylates thialysine and is not involved in polyamine metabolism

2004 ◽  
Vol 384 (1) ◽  
pp. 139-148 ◽  
Author(s):  
Catherine S. COLEMAN ◽  
Bruce A. STANLEY ◽  
A. Daniel JONES ◽  
Anthony E. PEGG
Keyword(s):  
Urinary Metabolites ◽  
Polyamine Metabolism ◽  
Polyamine Analogues ◽  
Naturally Occurring ◽  
Polyamine Content ◽  
Turn Over ◽  
Nih 3T3 ◽  
The Brain ◽  
Acetylpolyamine Oxidase ◽  
Catabolic Enzyme

Spermidine/spermine-N1-acetyltransferase (SSAT1) is a short-lived polyamine catabolic enzyme inducible by polyamines and polyamine analogues. Induction of SSAT1 plays an important role in polyamine homoeostasis, since the N1-acetylated polyamines can be excreted or oxidized by acetylpolyamine oxidase. We have purified a recombinant human acetyltransferase (SSAT2) that shares 45% identity and 61% homology with human SSAT1, but is only distally related to other known members of the GNAT (GCN5-related N-acetyltransferase) family. Like SSAT1, SSAT2 is widely expressed, but did not turn over rapidly, and levels were unaffected by treatments with polyamine analogues. Despite similarity in sequence to SSAT1, polyamines were found to be poor substrates of purified SSAT2, having Km values in the low millimolar range and kcat values of <0.01 s−1. The kcat/Km values for spermine and spermidine for SSAT2 were <0.0003% those of SSAT1. Expression of SSAT2 in NIH-3T3 cells was not detrimental to growth, and did not reduce polyamine content or increase acetylpolyamines. These results indicate that SSAT2 is not a polyamine catabolic enzyme, and that polyamines are unlikely to be its natural intracellular substrates. A promising candidate for the physiological substrate of SSAT2 is thialysine [S-(2-aminoethyl)-L-cysteine], which is acetylated predominantly at the ε-amino group with Km and kcat values of 290 μM and 5.2 s−1. Thialysine is a naturally occurring modified amino acid that can undergo metabolism to form cyclic ketimine derivatives found in the brain and as urinary metabolites, which can undergo further reaction to form antioxidants. SSAT2 should be renamed ‘thialysine Nε-acetyltransferase’, and may regulate this pathway.

scholarly journals Effect of a Bis-Benzyl Polyamine Analogue onPneumocystis carinii

2000 ◽  
Vol 44 (2) ◽  
pp. 337-343 ◽  
Author(s):  
Salim Merali ◽  
Muhamed Sarić ◽  
Kevin Chin ◽  
Allen B. Clarkson
Keyword(s):  
Mammalian Cells ◽  
Pneumocystis Carinii ◽  
Specific Treatment ◽  
Polyamine Metabolism ◽  
Biosynthetic Enzyme ◽  
Polyamine Biosynthesis ◽  
Polyamine Analogues ◽  
Polyamine Content ◽  
Polyamine Analogue ◽  
Polyamine Transporter

ABSTRACT Pneumocystis carinii is the causative agent of P. carinii pneumonia (PCP), an opportunistic infection associated with AIDS and other immunosuppressed conditions. Although polyamine metabolism of this fungus has been shown to be a chemotherapeutic target, this metabolism has not been thoroughly investigated. Reported here is the effect of one polyamine analogue,N,N′-bis{3-[(phenylmethyl)amino]propyl}-1,7-diaminoheptane (BBS), on P. carinii. BBS inhibits the growth of P. carinii in culture, but at concentrations higher than those required to inhibit the growth of other pathogens. However, BBS is at least as active in an animal model of PCP as in other models of diseases studied. BBS causes some reduction in P. cariniipolyamine content and polyamine biosynthetic enzyme activities, but the effect is less than that observed with other pathogens and very much less than the effect of the polyamine biosynthesis inhibitordl-α-difluoromethylornithine. BBS enters P. carinii cells via a polyamine transporter, unlike all other cells that have been studied. P. carinii cells do not remove the benzyl groups of BBS, as is reported for mammalian cells. The most likely mode of action is displacement of natural polyamines. Overall, the activity of BBS provides further evidence that polyamines and polyamine metabolism are rational targets for the development of drugs to treat PCP. Because the details of BBS-P. cariniiinteraction differ from those of other cells studied, polyamine analogues may provide a highly specific treatment for PCP.

scholarly journals The Emerging Clinical Role of Spermine in Prostate Cancer

2021 ◽  
Vol 22 (9) ◽  
pp. 4382
Author(s):  
Qiang Peng ◽  
Christine Yim-Ping Wong ◽  
Isabella Wai-yin Cheuk ◽  
Jeremy Yuen-Chun Teoh ◽  
Peter Ka-Fung Chiu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Polyamine Metabolism ◽  
Clinical Role ◽  
Polyamine Biosynthesis ◽  
Ongoing Research ◽  
Polyamine Analogues ◽  
Phenotype Transformation ◽  
And Function ◽  
Apoptosis Regulation

Spermine, a member of polyamines, exists in all organisms and is essential for normal cell growth and function. It is highly expressed in the prostate compared with other organs and is detectable in urine, tissue, expressed prostatic secretions, and erythrocyte. A significant reduction of spermine level was observed in prostate cancer (PCa) tissue compared with benign prostate tissue, and the level of urinary spermine was also significantly lower in men with PCa. Decreased spermine level may be used as an indicator of malignant phenotype transformation from normal to malignant tissue in prostate. Studies targeting polyamines and key rate-limiting enzymes associated with spermine metabolism as a tool for PCa therapy and chemoprevention have been conducted with various polyamine biosynthesis inhibitors and polyamine analogues. The mechanism between spermine and PCa development are possibly related to the regulation of polyamine metabolism, cancer-driving pathways, oxidative stress, anticancer immunosurveillance, and apoptosis regulation. Although the specific mechanism of spermine in PCa development is still unclear, ongoing research in spermine metabolism and its association with PCa pathophysiology opens up new opportunities in the diagnostic and therapeutic roles of spermine in PCa management.

Polyamine Metabolism inAcanthamoeba: Polyamine Content and Synthesis of Ornithine, Putrescine, and Diaminopropane1

1987 ◽  
Vol 34 (3) ◽  
pp. 278-284 ◽  
Author(s):  
BYEONG G. KIM ◽  
ANDREZJ SOBOTA ◽  
ALAN J. BITONTI ◽  
PETER P. McCANN ◽  
THOMAS J. BYERS
Keyword(s):  
Polyamine Metabolism ◽  
Polyamine Content

scholarly journals Superoxide Anion Production and Bioenergetic Profile in Young and Elderly Human Primary Myoblasts

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Mariangela Marrone ◽  
Rita Maria Laura La Rovere ◽  
Simone Guarnieri ◽  
Ester Sara Di Filippo ◽  
Giovanni Monaco ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxidative Phosphorylation ◽  
Energy Demand ◽  
The Elderly ◽  
Compensatory Mechanisms ◽  
Superoxide Anion Production ◽  
Age Related ◽  
Primary Myoblasts ◽  
Production Variability ◽  
And Function

Sarcopenia is the age-related loss of skeletal muscle mass, strength, and function. It is associated with regenerative difficulties by satellite cells, adult muscle stem cells, and alteration of oxidative management, mainly the increase in superoxide anions (O2•−). We aimed to investigate the relation between regenerative deficit in elderly and increase in O2•− production along with mitochondrial alterations. Myoblasts and myotubes from skeletal muscle of young and elderly healthy subjects (27.8 ± 6 and 72.4 ± 6.5 years old) were measured: (1) superoxide dismutase activity and protein content, (2) mitochondrial O2•− production levels, (3) O2•− production variability, and (4) mitochondrial bioenergetic profile. Compared to young myoblasts, elderly myoblasts displayed decreased SOD2 protein expression, elevated mitochondrial O2•− baseline levels, and decreased oxidative phosphorylation and glycolysis. Additionally, elderly versus young myotubes showed elevated mitochondrial O2•− levels when stressed with N-acetyl cysteine or high glucose and higher glycolysis despite showing comparable oxidative phosphorylation levels. Altogether, the elderly may have less metabolic plasticity due to the impaired mitochondrial function caused by O2•−. However, the increased energy demand related to the differentiation process appears to activate compensatory mechanisms for the partial mitochondrial dysfunction.

scholarly journals A de novo approach to disentangle partner identity and function in holobiont systems

2017 ◽  
Author(s):  
Arnaud Meng ◽  
Camille Marchet ◽  
Erwan Corre ◽  
Pierre Peterlongo ◽  
Adriana Alberti ◽  
...  
Keyword(s):  
Functional Diversity ◽  
De Novo ◽  
Model Organisms ◽  
Symbiotic Association ◽  
Proof Of Concept ◽  
Short Read ◽  
Symbiotic Associations ◽  
Functional Annotations ◽  
And Function ◽  
Similarity Method

AbstractBackgroundStudy of meta-transcriptomic datasets involving non-model organisms represents bioinformatic challenges. The production of chimeric sequences and our inability to distinguish the taxonomic origins of the sequences produced are inherent and recurrent difficulties in de novo assembly analyses. The study of holobiont transcriptomes shares similarities with meta-transcriptomic, and hence, is also affected by challenges invoked above. Here we propose an innovative approach to tackle such difficulties which was applied to the study of marine holobiont models as a proof of concept.ResultsWe considered three holobionts models, of which two transcriptomes were previously assembled and published, and a yet unpublished transcriptome, to analyze their raw reads and assign them to the host and/or to the symbiont(s) using Short Read Connector, a k-mer based similarity method. We were able to define four distinct categories of reads for each holobiont transcriptome: host reads, symbiont reads, shared reads and unassigned reads. The result of the independent assemblies for each category within a transcriptome led to a significant diminution of de novo assembled chimeras compared to classical assembly methods. Combining independent functional and taxonomic annotations of each partner’s transcriptome is particularly convenient to explore the functional diversity of an holobiont. Finally, our strategy allowed to propose new functional annotations for two well-studied holobionts and a first transcriptome from a planktonic Radiolaria-Dinophyta system forming widespread symbiotic association for which our knowledge is limited. ConclusionsIn contrast to classical assembly approaches, our bioinformatic strategy not only allows biologists to studying separately host and symbiont data from a holobiont mixture, but also generates improved transcriptome assemblies. The use of Short Read Connector has proven to be an effective way to tackle meta-transcriptomic challenges to study holobiont systems composed of either well-studied or poorly characterized symbiotic lineages such as the newly sequenced marine plankton Radiolaria-Dinophyta symbiosis and ultimately expand our knowledge about these marine symbiotic associations.

scholarly journals cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development

2019 ◽  
Vol 393 (2) ◽  
pp. 287-302 ◽  
Author(s):  
Andreas Friebe ◽  
Peter Sandner ◽  
Achim Schmidtko
Keyword(s):  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Cell Types ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Therapeutic Implications ◽  
Cellular Effects ◽  
Recent Developments ◽  
And Function ◽  
Messenger Molecule

AbstractCyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. cGMP targets a variety of downstream effector molecules and, thus, elicits a very broad variety of cellular effects. Its production is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC); both enzymes exist in different isoforms. cGMP-induced effects are regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). Depending on the distribution of sGC and pGC and the formation of ligands, this pathway regulates not only the cardiovascular system but also the kidney, lung, liver, and brain function; in addition, the cGMP pathway is involved in the pathogenesis of fibrosis, inflammation, or neurodegeneration and may also play a role in infectious diseases such as malaria. Moreover, new pharmacological approaches are being developed which target sGC- and pGC-dependent pathways for the treatment of various diseases. Therefore, it is of key interest to understand this pathway from scratch, beginning with the molecular basis of cGMP generation, the structure and function of both guanylyl cyclases and cGMP downstream targets; research efforts also focus on the subsequent signaling cascades, their potential crosstalk, and also the translational and, ultimately, the clinical implications of cGMP modulation. This review tries to summarize the contributions to the “9th International cGMP Conference on cGMP Generators, Effectors and Therapeutic Implications” held in Mainz in 2019. Presented data will be discussed and extended also in light of recent landmark findings and ongoing activities in the field of preclinical and clinical cGMP research.

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