Physiological importance of polyamines

Zygote ◽  
2017 ◽  
Vol 25 (3) ◽  
pp. 244-255 ◽  
Author(s):  
Yasser Y. Lenis ◽  
Mohammed A. Elmetwally ◽  
Juan G. Maldonado-Estrada ◽  
Fuller W. Bazer

SummaryPolyamines are polycationic molecules that contain two or more amino groups (–NH3+) and are present in all eukaryotic and prokaryotic cells. Polyamines are synthesized from arginine, ornithine, and proline, and from methionine as the methyl-group donor. In the traditional pathway for polyamine synthesis, arginase converts arginine into ornithine, which is decarboxylated by ornithine decarboxylase (ODC1) to generate putrescine. The latter is converted to spermidine and spermine. Recent studies have indicated the existence of ‘non-classical pathways’ for the generation of putrescine from arginine and proline in animal cells. Specifically, arginine decarboxylase (ADC) catalyzes the conversion of arginine into agmatine, which is hydrolyzed by agmatinase (AGMAT) to form putrescine. Additionally, proline is oxidized by proline oxidase to yield pyrroline-5-carboxylate, which undergoes transamination with glutamate to produce ornithine for decarboxylation by ODC1. Intracellular production of polyamines is controlled by antizymes binding to and inactivating ODC1. Polyamines exert effects that include stimulation of cell division and proliferation, gene expression for the survival of cells, DNA and protein synthesis, regulation of apoptosis, oxidative stress, angiogenesis, and cell–cell communication activity. Accordingly, polyamines are essential for early embryonic development and successful pregnancy outcome in mammals. In this paper the main concepts on the history, structure and molecular pathways of polyamines as well as their physiological role on angiogenesis, and reproductive physiology are reviewed.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Agnieszka Biernatowska ◽  
Paulina Olszewska ◽  
Krzysztof Grzymajło ◽  
Dominik Drabik ◽  
Sebastian Kraszewski ◽  
...  

AbstractFlotillins are the major structural proteins in erythroid raft domains. We have shown previously that the dynamic nanoscale organization of raft domains in erythroid cells may depend on flotillin-MPP1 interactions. Here, by using molecular dynamic simulations and a surface plasmon resonance-based approach we determined that high-affinity complexes of MPP1 and flotillins are formed via a so far unidentified region within the D5 domain of MPP1. Significantly, this particular “flotillin binding motif” is of key physiological importance, as overexpression of peptides containing this motif inhibited endogenous MPP1-flotillin interaction in erythroid precursor cells, thereby causing lateral disorganization of raft domains. This was reflected by both reduction in the plasma membrane order and markedly decreased activation of signal transduction via the raft-dependent insulin receptor pathway. Our data highlight new molecular details concerning the mechanism whereby MPP1 functionally links flotillins to exert their physiological role in raft domain formation.


2021 ◽  
Vol 23 ◽  
Author(s):  
Zhengyu Zhang ◽  
Ying Peng ◽  
Jiang Zheng

: Reactive metabolites (RMs) are products generated from the metabolism of endogenous and exogenous substances. RMs are characterized as electrophilic species chemically reactive to nucleophiles. Those nucleophilic species may be nitrogen-containing bio-molecules, including macro-biomolecules, such as protein and DNA, and small biomolecules, i.e., amino acids (AAs) and biogenic amines (BAs). AAs and BAs are essential endogenous nitrogen-containing compounds required for normal development, metabolism, and physiological functions in organisms, through participating in the intracellular replication, transcription, translation, division and proliferation, DNA and protein synthesis, regulation of apoptosis, and intercellular communication activities. These biological amines containing an active lone pair of electrons on the electronegative nitrogen atom would be the proper N-nucleophiles to be attacked by the abovementioned RMs. This review covers an overview of adductions of AAs and BAs with varieties of RMs. These RMs are formed from metabolic activation of furans, naphthalene, benzene, and products of lipid peroxidation. This article is designed to provide readers with a better understanding of biochemical mechanisms of toxic action.


1989 ◽  
Vol 44 (1-2) ◽  
pp. 49-54 ◽  
Author(s):  
Marbeth Christ ◽  
Hansruedi Felix ◽  
Jost Harr

Absract Several enzymes involved in polyamine biosynthesis namely ornithine, arginine and S-adenosylmethionine decarboxylase as well as spermidine synthase, were analyzed in partially purified wheat extracts. For all enzymes effective inhibitors were found. Among them the most interesting was l-aminooxy-3-aminopropane, which inhibited all three decarboxylases. Classical polyamine biosynthesis inhibitors like difluoromethylornithine, difluoromethylarginine. methyl glyoxal bis- (guanylhydrazone) and cyclohexylamine were also inhibitory on plant enzymes. A remarkable difference in the amount of arginine and ornithine decarboxylase existed in wheat. Arginine decarboxylase seems to be more important at least during the early stage of development. Influence of polyamine synthesis inhibitors on polyamine levels is more likely to come from arginine decarboxylase inhibitors. As inhibitors of all essential enzymes involved in plant polyamine biosynthesis were found, the study of the importance of polyamines in plant physiology will be considerably facilitated.


2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Teruhiko Matsubara

Glycoconjugates play various roles in biological processes. In particular, oligosaccharides on the surface of animal cells are involved in virus infection and cell-cell communication. Inhibitors of carbohydrate-protein interactions are potential antiviral drugs. Several anti-influenza drugs such as oseltamivir and zanamivir are derivatives of sialic acid, which inhibits neuraminidase. However, it is very difficult to prepare a diverse range of sugar derivatives by chemical synthesis or by the isolation of natural products. In addition, the pathogenic capsular polysaccharides of bacteria are carbohydrate antigens, for which a safe and efficacious method of vaccination is required. Phage-display technology has been improved to enable the identification of peptides that bind to carbohydrate-binding proteins, such as lectins and antibodies, from a large repertoire of peptide sequences. These peptides are known as “carbohydrate-mimetic peptides (CMPs)” because they mimic carbohydrate structures. Compared to carbohydrate derivatives, it is easy to prepare mono- and multivalent peptides and then to modify them to create various derivatives. Such mimetic peptides are available as peptide inhibitors of carbohydrate-protein interactions and peptide mimotopes that are conjugated with adjuvant for vaccination.


2019 ◽  
Vol 31 (7) ◽  
pp. 1228
Author(s):  
Jane C. Fenelon ◽  
Bruce D. Murphy

Implantation is essential for the establishment of a successful pregnancy, and the preimplantation period plays a significant role in ensuring implantation occurs in a timely and coordinated manner. This requires effective maternal–embryonic signalling, established during the preimplantation period, to synchronise development. Although multiple factors have been identified as present during this time, the exact molecular mechanisms involved are unknown. Polyamines are small cationic molecules that are ubiquitously expressed from prokaryotes to eukaryotes. Despite being first identified over 300 years ago, their essential roles in cell proliferation and growth, including cancer, have only been recently recognised, with new technologies and interest resulting in rapid expansion of the polyamine field. This review provides a summary of our current understanding of polyamine synthesis, regulation and function with a focus on recent developments demonstrating the requirements for polyamines during the establishment of pregnancy up to the implantation stage, in particular the role of polyamines in the control of embryonic diapause and the identification of an alternative pathway for their synthesis in sheep pregnancy. This, along with other novel discoveries, provides new insights into the control of the peri-implantation period in mammals and highlights the complexities that exist in regulating this critical period of pregnancy.


1988 ◽  
Vol 106 (3) ◽  
pp. 715-721 ◽  
Author(s):  
O Baron-Epel ◽  
D Hernandez ◽  
L W Jiang ◽  
S Meiners ◽  
M Schindler

Fluorescence photobleaching was employed to examine the intercellular movement of fluorescein and carboxyfluorescein between contiguous soybean root cells (SB-1 cell line) growing in tissue culture. Results of these experiments demonstrated movement of these fluorescent probes between cytoplasmic (symplastic) compartments. This symplastic transport was inhibited with Ca2+ in the presence of ionophore A23187, and also with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Both of these agents have previously been demonstrated to inhibit gap junction-mediated cell-cell communication in animal cells. In a companion experiment, a fluorescent phospholipid analogue, N-4-nitrobenzo-2-oxa-1,3-diazole phosphatidylcholine (NBD-PC), was incorporated into soybean cell membranes to examine whether dynamic membrane continuity existed between contacting cells, a transport route not existing between animal cells. Photobleaching single soybean cells growing in a filamentous strand demonstrated that phospholipid did exchange between contiguous cells.


2008 ◽  
Vol 51 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Pavel Tomšík ◽  
Alena Stoklasová ◽  
Stanislav Mičuda ◽  
Mohamed Niang ◽  
Petr Šuba ◽  
...  

The effect of unsubstituted deoxyhexoses, 2-deoxy-D-glucose (2-DG) and L-fucose, on tumor cells has been reported in several papers throughout the last decades. That of a similar deoxysugar, L-rhamnose, which is synthesized in bacteria and plants but not in animal cells, has until today not been explored. In the present study, we examined the effect of L-rhamnose on DNA and protein synthesis, growth and the potential induction of apoptosis of tumor cells in vitro. Using 2-DG for comparison, we studied the effect of L-rhamnose in concentrations up to 20 (32 resp.) mmol/l on the initial velocity of the incorporation of labeled precursors of DNA and proteins in short term cultures of both mouse Ehrlich ascites tumor (EAT) and human HL-60 cells in vitro, and further, on cell proliferation and apoptosis induction in HL-60 cells. Neither cytotoxic nor cytostatic effects of L-rhamnose were observed with the exception of slightly pronounced inhibition of DNA synthesis in EAT cells. From the lacking inhibition of the protein synthesis it can be considered that L-rhamnose does not interfere with energy metabolism, at least not in a similar manner as 2-DG.


1995 ◽  
Vol 6 (12) ◽  
pp. 1707-1719 ◽  
Author(s):  
B R Kwak ◽  
M M Hermans ◽  
H R De Jonge ◽  
S M Lohmann ◽  
H J Jongsma ◽  
...  

Studies on physiological modulation of intercellular communication mediated by protein kinases are often complicated by the fact that cells express multiple gap junction proteins (connexins; Cx). Changes in cell coupling can be masked by simultaneous opposite regulation of the gap junction channel types expressed. We have examined the effects of activators and inhibitors of protein kinase A (PKA), PKC, and PKG on permeability and single channel conductance of gap junction channels composed of Cx45, Cx43, or Cx26 subunits. To allow direct comparison between these Cx, SKHep1 cells, which endogenously express Cx45, were stably transfected with cDNAs coding for Cx43 or Cx26. Under control conditions, the distinct types of gap junction channels could be distinguished on the basis of their permeability and single channel properties. Under various phosphorylating conditions, these channels behaved differently. Whereas agonists/antagonist of PKA did not affect permeability and conductance of all gap junction channels, variable changes were observed under PKC stimulation. Cx45 channels exhibited an additional conductance state, the detection of the smaller conductance states of Cx43 channels was favored, and Cx26 channels were less often observed. In contrast to the other kinases, agonists/antagonist of PKG affected permeability and conductance of Cx43 gap junction channels only. Taken together, these results show that distinct types of gap junction channels are differentially regulated by similar phosphorylating conditions. This differential regulation may be of physiological importance during modulation of cell-to-cell communication of more complex cell systems.


1988 ◽  
Vol 254 (2) ◽  
pp. 373-378 ◽  
Author(s):  
S Nagarajan ◽  
B Ganem ◽  
A E Pegg

A number of synthetic polyamine derivatives that included five achiral gem-dimethylspermidines and two analogous tetramethylated spermines were tested for their abilities to serve as substrates for enzymes metabolizing polyamines and for their capacities to substitute for the natural polyamines in cell growth. It was found that none of the compounds were effective substrates for spermine synthase, and only one, namely 8,8-dimethylspermidine, was a substrate for spermidine/spermine N1-acetyltransferase. However, all of the spermidine derivatives and 1,1,12,12-tetramethylspermine were able to support the growth of SV-3T3 cells in which endogenous polyamine synthesis was prevented by the addition of alpha-difluoromethylornithine. These results suggest that either spermidine or spermine can support cell growth without the need for metabolic interconversion. In contrast with the result with 1,1,12,12-tetramethylspermine, 3,3,10,10-tetramethylspermine did not restore growth of polyamine-depleted SV-3T3 cells. Comparison of the properties of these derivatives may prove valuable in understanding the physiological role of polyamines.


2017 ◽  
Vol 216 (2) ◽  
pp. 463-476 ◽  
Author(s):  
Ayelén Mariana Distéfano ◽  
María Victoria Martin ◽  
Juan Pablo Córdoba ◽  
Andrés Martín Bellido ◽  
Sebastián D’Ippólito ◽  
...  

In plants, regulated cell death (RCD) plays critical roles during development and is essential for plant-specific responses to abiotic and biotic stresses. Ferroptosis is an iron-dependent, oxidative, nonapoptotic form of cell death recently described in animal cells. In animal cells, this process can be triggered by depletion of glutathione (GSH) and accumulation of lipid reactive oxygen species (ROS). We investigated whether a similar process could be relevant to cell death in plants. Remarkably, heat shock (HS)–induced RCD, but not reproductive or vascular development, was found to involve a ferroptosis-like cell death process. In root cells, HS triggered an iron-dependent cell death pathway that was characterized by depletion of GSH and ascorbic acid and accumulation of cytosolic and lipid ROS. These results suggest a physiological role for this lethal pathway in response to heat stress in Arabidopsis thaliana. The similarity of ferroptosis in animal cells and ferroptosis-like death in plants suggests that oxidative, iron-dependent cell death programs may be evolutionarily ancient.


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