scholarly journals Altered polyamine metabolism in the PRO/Re strain of inbred mice

1976 ◽  
Vol 158 (3) ◽  
pp. 529-533 ◽  
Author(s):  
C A Manen ◽  
R L Blake ◽  
D H Russell
Keyword(s):  
Biosynthetic Pathway ◽  
Inbred Mice ◽  
Proline Accumulation ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Polyamine Biosynthesis ◽  
Male And Female ◽  
Adenosylmethionine Decarboxylase ◽  
Significant Difference ◽  
High Concentrations

The PRO/Re strain of inbred mice are characterized by abnormally high concentrations of proline in both blood (hyperprolinaemia) and urine (prolinuria). They excrete increased amounts of polyamines in their urine. Male PRO/Re mice excreted putrescine at 175% and spermidine at 300% the amount of male C57BL/6J controls. Female PRO/Re mice excreted putrescine at 115% and spermidine at 150% of the amount in the urine of female controls. Examination of the enzymes involved in polyamine biosynthesis revealed that ornithine decarboxylase, the initial enzyme in the polyamine-biosynthetic pathway, was increased by 150% in the kidneys and by 100% in the liver of male PRO/Re mice. There was no significant difference between PRO/Re and C57BL/6J male mice for either putrescine- or spermidine-stimulated S-adenosylmethionine decarboxylase activity. Female PRO/Re mice showed no significant difference from female C57BL/6J mice for any of the enzymes examined. When the concentrations of the polyamines in the tissues of the PRO/Re mice were determined, spermidine and spermine concentrations in the kidneys of the male PRO/Re mice were twice those of the controls. Spermidine concentration in the livers of both male and female PRO/Re mice was approx. 130% that of the controls. Polyamine concentrations in the brains were similar in controls and mutants. The increased polyamine biosynthesis and excretion in the PRO/Re mutant mice may be a mechanism to decrease the extent of proline accumulation.

scholarly journals Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities

2011 ◽  
Vol 438 (2) ◽  
pp. 229-244 ◽  
Author(s):  
Lyn-Marie Birkholtz ◽  
Marni Williams ◽  
Jandeli Niemand ◽  
Abraham I. Louw ◽  
Lo Persson ◽  
...  
Keyword(s):  
Drug Targets ◽  
Current Knowledge ◽  
New Drugs ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Thiol Metabolism ◽  
Potential Drug Targets ◽  
Unique Compound

New drugs are urgently needed for the treatment of tropical and subtropical parasitic diseases, such as African sleeping sickness, Chagas' disease, leishmaniasis and malaria. Enzymes in polyamine biosynthesis and thiol metabolism, as well as polyamine transporters, are potential drug targets within these organisms. In the present review, the current knowledge of unique properties of polyamine metabolism in these parasites is outlined. These properties include prozyme regulation of AdoMetDC (S-adenosylmethionine decarboxylase) activity in trypanosomatids, co-expression of ODC (ornithine decarboxylase) and AdoMetDC activities in a single protein in plasmodia, and formation of trypanothione, a unique compound linking polyamine and thiol metabolism in trypanosomatids. Particularly interesting features within polyamine metabolism in these parasites are highlighted for their potential in selective therapeutic strategies.

scholarly journals Overexpression of arginine decarboxylase in transgenic plants

1997 ◽  
Vol 325 (2) ◽  
pp. 331-337 ◽  
Author(s):  
Daniel BURTIN ◽  
Anthony J. MICHAEL
Keyword(s):  
Transgenic Plants ◽  
Arginine Decarboxylase ◽  
Polyamine Metabolism ◽  
Morphological Development ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Two Generations ◽  
Key Enzyme ◽  
Polyamine Conjugate ◽  
And Control

The activity of arginine decarboxylase (ADC), a key enzyme in plant polyamine biosynthesis, was manipulated in two generations of transgenic tobacco plants. Second-generation transgenic plants overexpressing an oat ADC cDNA contained high levels of oat ADC transcript relative to tobacco ADC, possessed elevated ADC enzyme activity and accumulated 10–20-fold more agmatine, the direct product of ADC. In the presence of high levels of the precursor agmatine, no increase in the levels of the polyamines putrescine, spermidine and spermine was detected in the transgenic plants. Similarly, the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase were unchanged. No diversion of polyamine metabolism into the hydroxycinnamic acid–polyamine conjugate pool or into the tobacco alkaloid nicotine was detected. Activity of the catabolic enzyme diamine oxidase was the same in transgenic and control plants. The elevated ADC activity and agmatine production were subjected to a metabolic/physical block preventing increased, i.e. deregulated, polyamine accumulation. Overaccumulation of agmatine in the transgenic plants did not affect morphological development.

scholarly journals Role of pyridoxal phosphate in mammalian polyamine biosynthesis. Lack of requirement for mammalian S-adenosylmethionine decarboxylase activity

1977 ◽  
Vol 166 (1) ◽  
pp. 81-88 ◽  
Author(s):  
A E Pegg
Keyword(s):  
Ornithine Decarboxylase ◽  
Pyridoxal Phosphate ◽  
Vitamin B ◽  
Decarboxylase Activity ◽  
Deficient Diet ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Ornithine Decarboxylase Activity

1. Polyamine concentrations were decreased in rats fed on a diet deficient in vitamin B-6. 2. Ornithine decarboxylase activity was decreased by vitamin B-6 deficiency when assayed in tissue extracts without addition of pyridoxal phosphate, but was greater than in control extracts when pyridoxal phosphate was present in saturating amounts. 3. In contrast, the activity of S-adenosylmethionine decarboxylase was not enhanced by pyridoxal phosphate addition even when dialysed extracts were prepared from tissues of young rats suckled by mothers fed on the vitamin B-6-deficient diet. 4. S-Adenosylmethionine decarboxylase activities were increased by administration of methylglyoxal bis(guanylhydrazone) (1,1′-[(methylethanediylidine)dinitrilo]diguanidine) to similar extents in both control and vitamin B-6-deficient animals. 5. The spectrum of highly purified liver S-adenosylmethionine decarboxylase did not indicate the presence of pyridoxal phosphate. After inactivation of the enzyme by reaction with NaB3H4, radioactivity was incorporated into the enzyme, but was not present as a reduced derivative of pyridoxal phosphate. 6. It is concluded that the decreased concentrations of polyamines in rats fed on a diet containing vitamin B-6 may be due to decreased activity or ornithine decarboxylase or may be caused by an unknown mechanism responding to growth retardation produced by the vitamin deficiency. In either case, measurements of S-adenosylmethionine decarboxylase and ornithine decarboxylase activity under optimum conditions in vitro do not correlate with the polyamine concentrations in vivo.

Inhibitors Influencing Plant Enzymes of the Polyamine Biosynthetic Pathway

1989 ◽  
Vol 44 (1-2) ◽  
pp. 49-54 ◽  
Author(s):  
Marbeth Christ ◽  
Hansruedi Felix ◽  
Jost Harr
Keyword(s):  
Biosynthetic Pathway ◽  
Early Stage ◽  
Arginine Decarboxylase ◽  
Polyamine Biosynthesis ◽  
Polyamine Synthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Stage Of Development ◽  
Decarboxylase Inhibitors ◽  
Plant Enzymes ◽  
To Come

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.

scholarly journals Regulation of S-adenosylmethionine decarboxylase activity by alterations in the intracellular polyamine content

1992 ◽  
Vol 288 (2) ◽  
pp. 511-518 ◽  
Author(s):  
L M Shantz ◽  
I Holm ◽  
O A Jänne ◽  
A E Pegg
Keyword(s):  
Cho Cells ◽  
Translational Regulation ◽  
Decarboxylase Activity ◽  
Origin Of Replication ◽  
Sv40 Promoter ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Mammalian Cell Lines ◽  
Sv40 Origin ◽  
Polyamine Content

The effects of addition of exogenous spermidine and spermine and of two inhibitors of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), which decreases spermidine concentrations, and n-butyl-1,3-diaminopropane, which depletes spermine, on the expression of S-adenosylmethionine decarboxylase (AdoMetDC) activity were studied in mammalian cell lines (HT29, CHO and COS-7). AdoMetDC levels were inversely related to the polyamine content, and spermine was the more potent repressor of AdoMetDC activity, but only spermidine affected the amount of AdoMetDC mRNA. Transfection of COS-7 cells or CHO cells with plasmid constructs containing a chloramphenicol acetyltransferase (CAT) reporter gene driven by portions of the AdoMetDC promoter region indicated that CAT expression was altered by spermidine, but not by spermine, suggesting that there is a spermidine-responsive element in this promoter. Transient transfection of COS-7 cells with pSAMh1, a plasmid containing the AdoMetDC cDNA in a vector with the SV40 promoter and origin of replication, led to a large increase in AdoMetDC expression. Although treatment of COS-7 cells with n-butyl-1,3-diaminopropane greatly increased endogenous AdoMetDC activity, the spermine depletion brought about by this inhibitor did not stimulate AdoMetDC expression from pSAMh1. The pSAMh1 cDNA is missing 72 nucleotides from the 5′ end of the AdoMetDC mRNA, and it is possible that translational regulation by spermine involves this region. The expression of AdoMetDC from pSAMh1 in COS-7 cells was greatly inhibited by DFMO treatment, although endogenous AdoMetDC activity was increased. The expression of other plasmids containing the SV40 origin of replication was also inhibited by DFMO in COS-7 cells, but not in CHO cells. DFMO treatment did not interfere with the expression of plasmids driven by the RSV promoter. These results suggest that low spermidine levels interfere with the replication of plasmids containing the SV40 origin of replication.

scholarly journals The influence of nerve section on the metabolism of polyamines in rat diaphragm muscle

1981 ◽  
Vol 196 (2) ◽  
pp. 603-610 ◽  
Author(s):  
D Hopkins ◽  
K L Manchester
Keyword(s):  
Ornithine Decarboxylase ◽  
Normal Values ◽  
Methionine Adenosyltransferase ◽  
Diaphragm Muscle ◽  
Regulatory Mechanisms ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Rat Diaphragm ◽  
Nerve Section ◽  
Adenosylmethionine Decarboxylase

Concentrations of spermidine, spermine and putrescine have been measured in rat diaphragm muscle after unilateral nerve section. The concentration of putrescine increased approx. 10-fold 2 days after nerve section, that of spermidine about 3-fold by day 3, whereas an increase in the concentration of spermine was only observed after 7-10 days. It was not possible to show enhanced uptake of either exogenous putrescine or spermidine by the isolated tissue during the hypertrophy. Consistent with the accumulation of putrescine, activity of ornithine decarboxylase increased within 1 day of nerve section, was maximally elevated by the second day and then declined. Synthesis of spermidine from [14C]putrescine and either methionine or S-adenosylmethionine bt diaphragm cytosol rose within 1 day of nerve section, but by day 3 had returned to normal or below normal values. Activity of adenosylmethionine decarboxylase similarly increased within 1 day of nerve section, but by day 3 had declined to below normal values. Activity of methionine adenosyltransferase was elevated throughout the period studied. The concentration of S-adenosylmethionine was likewise enhanced during hypertrophy. Administration of methylglyoxal bis(guanylhydrazone) produced a marked increase in adenosylmethionine decarboxylase activity and a large increase in putrescine concentration, but did not prevent the rise in spermidine concentration produced by denervation. Possible regulatory mechanisms of polyamine metabolism consistent with the observations are discussed.

scholarly journals Selective regulation of S-adenosylmethionine decarboxylase activity by the spermine analogue 6-spermyne

1988 ◽  
Vol 254 (2) ◽  
pp. 337-342 ◽  
Author(s):  
C W Porter ◽  
J McManis ◽  
D Lee ◽  
R J Bergeron
Keyword(s):  
Binding Sites ◽  
Enzyme Activities ◽  
Decarboxylase Activity ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
L1210 Cells ◽  
Initial Decrease ◽  
Function Correlation ◽  
Apparent Ability ◽  
Interesting Structure

Polyamine-biosynthesis activity is known to be negatively regulated by intracellular polyamine pools. Accordingly, treatment of cultured L1210 cells with 10 microM-spermine rapidly and significantly lowered ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) activities in a sequential manner. By contrast, treatment for 48 h with 10 microM of the unsaturated spermine analogue 6-spermyne lowered AdoMetDC activity, but not ODC activity. An initial decrease in ODC activity at 2 h was attributed to a transient increase in free intracellular spermidine and spermine brought about through their displacement by the analogue. Thereafter, ODC activity recovered steadily to control values as 6-spermyne pools increased and spermidine and spermine pools decreased owing to analogue suppression of AdoMetDC activity. The apparent ability of 6-spermyne to regulate AdoMetDC, but not ODC, activity suggests an interesting structure-function correlation and demonstrates that the typical co-regulation of these enzyme activities can be dissociated. This, in turn, may reflect the existence of independent regulatory binding sites for the two enzymes.

INFLUENCE OF DIETARY ORNITHINE AND METHIONINE ON GROWTH, CARCASS COMPOSITION, AND POLYAMINE METABOLISM IN THE CHICK

1981 ◽  
Vol 61 (4) ◽  
pp. 1005-1012 ◽  
Author(s):  
T. K. SMITH
Keyword(s):  
Soy Protein ◽  
Control Diet ◽  
Carcass Composition ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Chick Growth ◽  
Polyamine Synthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Regulatory Enzymes ◽  
Increased Activity

Experiments were conducted to determine the effects of factorial combinations of dietary ornithine and methionine on chick growth, carcass composition, and the regulatory enzymes of polyamine synthesis. Week-old leghorn cockerel chicks were fed 12 soy protein-based semipurified diets containing 0.00, 0.50, 0.85 or 1.25% ornithine plus 0.55, 0.75 or 1.00% methionine for 2 wk. Weight gains were depressed as dietary methionine increased but only when ornithine was fed at less than 0.85%. Ornithine supplements depressed growth regardless of methionine levels. Carcass protein decreased with supplemental ornithine when methionine was fed at 0.55% but not at higher levels. Methionine supplements decreased carcass protein only in the absence of ornithine. Feeding 0.85% ornithine plus 0.55% methionine resulted in increased activity of S-adenosylmethionine decarboxylase in heart, pancreas, and muscle when compared to the control diet containing 0.00% ornithine plus 0.55% methionine. Dietary ornithine supplements lowered ornithine decarboxylase activities in heart, pancreas, and liver regardless of methionine level. It can be concluded that there is a nutritional interrelationship between ornithine and methionine as indicated by their cumulative effects on growth, carcass composition, and S-adenosylmethionine decarboxylase activity.

scholarly journals Inhibition by derivatives of diguanidines of cell proliferation in Ehrlich ascites cells grown in cultures

1980 ◽  
Vol 188 (2) ◽  
pp. 491-501 ◽  
Author(s):  
L Alhonen-Hongisto ◽  
H Pösö ◽  
J Jänne
Keyword(s):  
Growth Inhibition ◽  
Ehrlich Ascites Carcinoma ◽  
Tumour Cells ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Subsequent Formation ◽  
Adenosylmethionine Decarboxylase ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Cells ◽  
In Cells

The anti-proliferative effects of 1,1′-[(methylethanediylidene)dinitrilo]diguanidine [methylglyoxal bis(guanylhydrazone)] and 1,1′-[(metHYLETHANEDIYLIDENE)dinitrilo]bis-(3-aminoguaNIDINE) HAVE BEEN STUDIED IN Ehrlich ascites carcinoma cells grown in suspension cultures. Both compounds are potent inhibitors of S-adenosyl-L-methionine decarboxylase from the tumour cells. In the presence of putrescine (but not in its absence), the inhibition produced by 1,1′-[methylethanediylidene)dinitrilo]bis-(3-aminoguanadine) was apparently irreversible, as judged by persistent depression of the enzyme activity even after extensive dialysis. The two compounds produced similar increases in adenosylmethionine decarboxylase activity, which resulted from a striking stabilization of the enzyme in cells grown in the presence of the drugs. The inhibitory effect of the two diguanidine derivatives on the synthesis of DNA and protein became evident after an exposure of 4–8 h. At that time, the only change seen in tumour polyamines in cells grown in the presence of the inhibitors was an increase in cellular putrescine. To find out whether the compounds initially interfered with the energy production of the tumour cells, the cultures were grown in the presence of uniformly labelled glucose, and the formation of lactate, as well as the oxidation of the sugar into CO2, were measured. The activation of glycolysis upon dilution of the tumour cells with fresh medium and the subsequent formation of labelled CO2 were siliar in control cells and in cells exposed to methylglyoxal bis(buanylhydrazone), 1,1′-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) or diaminopropanol. Only a marginal decrease in the cellular content of ATP was found in cells exposed to the inhibitors for 24 h. The diguanidine-induced growth inhibition was fully reversed by low concentrations of exogenous polyamines. However, the possibility remained that the reversal by polyamines was due to a decrease of intracellular diguanidine concentration. Our results indicate that the mode of action of 1,1′-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) is fully comparable to that of methylglyoxal bis(guanylhydrazone), as regards stabilization of adenosylmethionine decarboxylase and the appearance of growth inhibition in Ehrlich ascites cells. The data tend to support the view that both compounds apparently have an early anti-proliferative effect unrelated to polyamine metabolism.

scholarly journals Role of propylamine transferases in hormone-induced stimulation of polyamine biosynthesis

1980 ◽  
Vol 192 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Kirsti Käpyaho ◽  
Hannu Pösö ◽  
Juhani Jänne
Keyword(s):  
Seminal Vesicle ◽  
Ornithine Decarboxylase ◽  
Ovarian Tissue ◽  
Ventral Prostate ◽  
Decarboxylase Activity ◽  
Spermidine Synthase ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Spermine Synthase ◽  
Stimulation Of

The effect of various hormones on the activities of the four enzymes engaged with the biosynthesis of the polyamines has been investigated in the rat. Human choriogonadotropin induced a dramatic, yet transient, stimulation of l-ornithine decarboxylase (EC 4.1.1.17) activity in rat ovary, with no or only marginal changes in the activities of S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50), spermidine synthase (aminopropyltransferase; EC 2.5.1.16) or spermine synthase. A single injection of oestradiol into immature rats maximally induced uterine ornithine decarboxylase at 4h after the injection. This early stimulation of ornithine decarboxylase activity was accompanied by a distinct enhancement of adenosylmethionine decarboxylase activity and a decrease in the activities of spermidine synthase and spermine synthase. In the seminal vesicle of castrated rats, testosterone treatment elicited a striking and persistent stimulation of ornithine decarboxylase and adenosylmethionine decarboxylase activities. The activity of spermidine synthase likewise rapidly increased between the first and the second day after the commencement of the hormone treatment, whereas the activity of spermine synthase remained virtually unchanged during the whole period of observation. Testosterone-induced changes in polyamine formation in the ventral prostate were comparable with those found in the seminal vesicle, with the possible exception of a more pronounced stimulation of spermidine synthase activity. It thus appears that an enhancement in one or both of the propylamine transferase (aminopropyltransferase) activities in response to hormone administration is an indicator of hormone-dependent growth (uterus and the male accessory sexual glands), and is not necessarily associated with non-proliferative hormonal responses, such as gonadotropin-induced luteinization of the ovarian tissue.

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