Polyamine oxidases — enzymes of unknown function?

Morgan, David M. L.

doi:10.1042/bst0260586

Cited by 15 publications

(6 citation statements)

References 10 publications

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“…The production of acrolein by β elimination from the products of the plasma amine oxidase reaction, N ′-(4-aminobutyl)-aminopropionaldehyde and N , N ′-bis(3-propionaldehye-1,4-butanediamine) (Figure ), and its potential role in their toxicity were reported more than 40 years ago. ,− The importance of acrolein formation as a major factor in the toxicity of terminally oxidized polyamines was strongly supported by studies of the kinetics of the inhibition of bacterial macromolecular synthesis by spermine in the presence of serum amine oxidases . Although there are a few claims disputing the role of acrolein formation (discussed in refs and ), many recent studies have confirmed the pioneering experiments of Kimes and Morris showing that, at low concentrations similar to those generated in the enzymatic oxidation reactions, acrolein is the key toxic intermediate from polyamine catabolism. , Acrolein can also be formed spontaneously from the SMO product 3-aminopropanal with the elimination of ammonia (Figure ). , The extent to which this conversion occurs in a cellular context, where enzymatic reduction or the direct reaction with cellular components provides alternate routes to its disposition, is not yet fully established. However, as described below, there is good evidence of the production of acrolein under conditions where SMO is active.…”

Section: Toxicity Of Polyamine Oxidation Productsmentioning

confidence: 98%

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Toxicity of Polyamines and Their Metabolic Products

Pegg

2013

Chem. Res. Toxicol.

243

199

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Polyamines are ubiquitous and essential components of mammalian cells. They have multiple functions including critical roles in nucleic acid and protein synthesis, gene expression, protein function, protection from oxidative damage, the regulation of ion channels, and maintenance of the structure of cellular macromolecules. It is essential to maintain a correct level of polyamines, and this amount is tightly regulated at the levels of transport, synthesis, and degradation. Catabolic pathways generate reactive aldehydes including acrolein and hydrogen peroxide via a number of oxidases. These metabolites, particularly those from spermine, can cause significant toxicity with damage to proteins, DNA, and other cellular components. Their production can be increased as a result of infection or cell damage that releases free polyamines and activates the oxidative catabolic pathways. Since polyamines also have an important physiological role in protection from oxidative damage, the reduction in polyamine content may exacerbate the toxic potential of these agents. Increases in polyamine catabolism have been implicated in the development of diseases including stroke, other neurological diseases, renal failure, liver disease, and cancer. These results provide new opportunities for the early diagnosis, prevention, and treatment of disease.

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Section: Toxicity Of Polyamine Oxidation Productsmentioning

confidence: 98%

“…A variety of oxidases are known that can degrade polyamines. − Some of these such as diamine oxidase and a serum amine oxidase have been known for almost a hundred years. Others such as spermine oxidase (SMO) were discovered only in the past decade.…”

Section: Oxidases Attacking Polyaminementioning

confidence: 99%

Toxicity of Polyamines and Their Metabolic Products

Pegg

2013

Chem. Res. Toxicol.

243

199

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“…Acetylation removes the positive charge on the amino group, and consequently acetylated polyamines are less potent than the parent molecules. Acetylated spermine is cleaved into spermidine through the action of a flavin adenine dinucleotide (FAD)-dependent polyamine oxidase [5, 14,21]. Similarly, spermidine is acetylated and cleaved by this polyamine oxidase back into putrescine, completing the backward conversion of spermine to putrescine.…”

Section: Introductionmentioning

confidence: 99%

Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications

Thomas¹

2001

CMLS, Cell. Mol. Life Sci.

780

577

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Polyamines are aliphatic cations with multiple functions and are essential for life. Cellular polyamine levels are regulated by multiple pathways such as synthesis from amino acid precursors, cellular uptake mechanisms that salvage polyamines from diet and intestinal microorganisms, as well as stepwise degradation and efflux. Investigations using polyamine biosynthetic inhibitors indicate that alterations in cellular polyamine levels modulate normal and cancer cell growth. Studies using transgenic mice overexpressing polyamine biosynthetic enzymes support a role of polyamines in carcinogenesis. Many, if not all, signal transduction pathways intersect with polyamine biosynthetic pathways and the regulation of intracellular polyamine levels. Direct binding of polyamines to DNA and their ability to modulate DNA-protein interactions appear to be important in the molecular mechanisms of polyamine action in cell proliferation. Consistent with the role of polyamines as facilitators of cell growth, several studies have shown their ability to protect cells from apoptosis. However, polyamines also have a role in facilitating cell death. The basis of these diverse cellular responses is currently not known. Cell death response might be partly mediated by the production of hydrogen peroxide during polyamine catabolism. In addition, the ability of polyamines to alter DNA-protein and protein-protein interactions might be disruptive to cellular functions, when abnormally high levels are accumulated due to defects in polyamine catabolic or efflux pathways. A large body of data indicates that polyamine pathway can be a molecular target for therapeutic intervention in several types cancers. Inhibitors of biosynthesis, polyamine analogues as well as oligonucleotide/polyamine analogue combinations are promising drug candidates for chemoprevention and/or treatment of cancer.

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“…containing polyamine oxidases and copper-containing diamine oxidases play major roles (Morgan, 1998(Morgan, , 1999. Polyamine oxidase in mammalian cells can convert spermine and spermidine, by oxidative cleavage, back to spermidine and putrescine, respectively, resulting in the formation of hydrogen peroxide through the following pathway.…”

Section: Polyamines In Hypersensitive Cell Deathmentioning

confidence: 99%

Induction of Hypersensitive Cell Death by Hydrogen Peroxide Produced through Polyamine Degradation in Tobacco Plants

2003

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Screening immediate-early responding genes during the hypersensitive response (HR) against tobacco mosaic virus infection in tobacco (Nicotiana tabacum) plants, we identified a gene encoding ornithine decarboxylase. Subsequent analyses showed that other genes involved in polyamine biosynthesis were also up-regulated, resulting in the accumulation of polyamines in apoplasts of tobacco mosaic virus-infected leaves. Inhibitors of polyamine biosynthesis, ␣-difluoromethyl-ornithine, however, suppressed accumulation of polyamines, and the rate of HR was reduced. In contrast, polyamine infiltration into a healthy leaf induced the generation of hydrogen peroxide and simultaneously caused HR-like cell death. Polyamine oxidase activity in the apoplast increased up to 3-fold that of the basal level during the HR, and its suppression with a specific inhibitor, guazatine, resulted in reduced HR. Because it is established that hydrogen peroxide is one of the degradation products of polyamines, these results indicate that one of the biochemical events in the HR is production of polyamines, whose degradation induces hydrogen peroxide, eventually resulting in hypersensitive cell death.

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Polyamine oxidases — enzymes of unknown function?

Cited by 15 publications

References 10 publications

Toxicity of Polyamines and Their Metabolic Products

Toxicity of Polyamines and Their Metabolic Products

Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications

Induction of Hypersensitive Cell Death by Hydrogen Peroxide Produced through Polyamine Degradation in Tobacco Plants

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