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.

Polyamine synthesis in liver and kidney of flounder in response to methylmercury

1976 ◽  
Vol 231 (2) ◽  
pp. 560-564 ◽  
Author(s):  
CA Manen ◽  
B Schmidt-Nielsen ◽  
DH Russell
Keyword(s):  
Ornithine Decarboxylase ◽  
Single Injection ◽  
Recovery Phase ◽  
Winter Flounder ◽  
Decarboxylase Activity ◽  
Pseudopleuronectes Americanus ◽  
Toxic Dose ◽  
Polyamine Synthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Liver And Kidney

The effect of methylmercury administration on polyamine synthesis was studied in the liver and kidney of the winter flounder (Pseudopleuronectes americanus). A single injection of methylmercury resulted in five- and sevenfold elevations of ornithine decarboxylase activity in the liver and kidney within 15 and 45 h, respectively. There were elevations of both putrescine- and spermidine-stimulated S-adenosylmethionine decarboxylase activities (approximately 1.5-fold) in both tissues. Evaluation of the polyamine accumulation patterns in these tissues indicated that in the liver all three polyamines increased in concentration until 48 h and then decline. In the kidney, the concentration of putrescine increased steadily until it was 200% of control at 72 h and then declined. Spermidine concentration decreased throughout the time studied and was 17% of control at 1 wk. There was no significant change in the concentration of spermine throughout the period studied. The changes in the polyamine pools and in the activities of the polyamine biosynthetic enzymes after methylmercury administration are consistent with an involvement of the polyamines in the recovery phase to a toxic dose of methylmercury.

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 Protective role of fructose 1,6-bisphosphate during CCl4 hepatotoxicity in rats

1989 ◽  
Vol 262 (3) ◽  
pp. 721-725 ◽  
Author(s):  
S B Rao ◽  
H M Mehendale
Keyword(s):  
Tissue Repair ◽  
Protective Role ◽  
Polyamine Metabolism ◽  
Polyamine Synthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Intermediary Metabolite ◽  
Ccl4 Treatment ◽  
Hepatocellular Regeneration ◽  
Fructose 1,6 Bisphosphate

Rats were injected intraperitoneally with CCl4 (2.5 ml/kg body wt.) and the hepatotoxicity was compared with that of rats receiving the same dose of CCl4 and an intraperitoneal injection of fructose 1,6-bisphosphate (2 g/kg body wt.). A 50-70% decrease in plasma aspartate aminotransferase and alanine aminotransferase activities was observed in the latter treatment, indicating a protective role of the sugar bisphosphate in CCl4 hepatotoxicity. The protection was accompanied by elevated hepatic activities of ornithine decarboxylase at 2, 6 and 24 h, S-adenosylmethionine decarboxylase at 6 h, and spermidine N1-acetyltransferase at 2 h. The increase in the enzymes involved in polyamine metabolism was shown in our previous work [Rao, Young & Mehendale (1989) J. Biochem. Toxicol. 4, 55-63] to correlate with increased polyamine synthesis or interconversion, which was related to the extent of hepatocellular regeneration. The hepatic contents of fructose 1,6-bisphosphate and ATP significantly decreased after CCl4 treatment, and administration of the sugar bisphosphate increased hepatic ATP. Fructose 1,6-bisphosphate, an intermediary metabolite of the glycolytic pathway, may decrease CCl4 toxicity by increasing the ATP in the hepatocytes. The ATP generated is useful for hepatocellular regeneration and tissue repair, events which enable the liver to overcome CCl4 injury.

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.

S-Adenosylmethionine decarboxylase

2009 ◽  
Vol 46 ◽  
pp. 25-46 ◽  
Author(s):  
Anthony E. Pegg
Keyword(s):  
Subunit Composition ◽  
Decarboxylase Activity ◽  
Primary Sequence ◽  
Prosthetic Group ◽  
Polyamine Synthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Decarboxylation Reaction ◽  
Key Enzyme ◽  
Covalently Bound

S-Adenosylmethionine decarboxylase is a key enzyme for the synthesis of polyamines in mammals, plants and many other species that use aminopropyltransferases for this pathway. It catalyses the formation of S-adenosyl-1-(methylthio)-3-propylamine (decarboxylated S-adenosylmethionine), which is used as the aminopropyl donor. This is the sole function of decarboxylated S-adenosylmethionine. Its content is therefore kept very low and is regulated by variation in the activity of S-adenosylmethionine decarboxylase according to the need for polyamine synthesis. All S-adenosylmethionine decarboxylases have a covalently bound pyruvate prosthetic group, which is essential for the decarboxylation reaction, and have similar structures, although they differ with respect to activation by cations, primary sequence and subunit composition. The present chapter describes these features, the mechanisms for autocatalytic generation of the pyruvate from a proenzyme precursor and for the decarboxylation reaction, and the available inhibitors of this enzyme, which have uses as anticancer and anti-trypanosomal agents. The intricate mechanisms for regulation of mammalian S-adenosylmethionine decarboxylase activity and content are also described.

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 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 metabolism in liver of young rats

1978 ◽  
Vol 174 (3) ◽  
pp. 727-732 ◽  
Author(s):  
M E Brosnan ◽  
G W Symonds ◽  
D E Hall ◽  
D L Symonds
Keyword(s):  
Fold Increase ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Adult Rats ◽  
Adenosylmethionine Decarboxylase ◽  
Dna And Rna ◽  
Rat Pups ◽  
Old Rats ◽  
Rna Accumulation ◽  
Number Of Cells

Rat liver undergoes a phase of rapid growth during weaning. We followed the changes in polyamine metabolism occurring during this period of natural growth, and compared them with changes in DNA and RNA accumulation. There was a 2.5-fold increase in the number of cells per liver between suckling (18–19 days old) and weaning (30–32 days old) rats. Ornithine decarboxylase activity increased from the low value in 18-day-old rat pups and remained significantly higher (approx. 5–10-fold) than that in adult rats from day 21 to day 34. Putrescine-dependent S-adenosylmethionine decarboxylase activity was slightly but significantly increased during most of this period. Spermidine and RNA concentrations fluctuated in concert, whereas spermine content per cell doubled during the period from day 23 to day 30.

scholarly journals Effect on prostatic growth of 2-difluoromethylornithine, an effective inhibitor of ornithine decarboxylase

1982 ◽  
Vol 202 (1) ◽  
pp. 175-181 ◽  
Author(s):  
C Danzin ◽  
N Claverie ◽  
J Wagner ◽  
J Grove ◽  
J Koch-Weser
Keyword(s):  
Ornithine Decarboxylase ◽  
Ventral Prostate ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Irreversible Inhibitor ◽  
Adult Rats ◽  
Adenosylmethionine Decarboxylase ◽  
Dna Contents ◽  
Wet Weight ◽  
Rna And Dna

2-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, causes marked changes in the polyamine metabolism of ventral prostate when given to adult rats in drinking water (20 g/l) for 3 consecutive days. A 90% inhibition of ornithine decarboxylase activity is accompanied by approx. 80% decreases of the concentrations of putrescine and spermidine and by a 36% decrease in spermine. Concomitantly, S-adenosylmethionine decarboxylase activity increases 7-fold and the concentration of decarboxylated S-adenosylmethionine 450-fold. When DFMO is given to immature rats for 12 consecutive days the above described changes are accompanied by a marked reduction in the age-dependent increases of the wet weight and RNA and DNA contents of the ventral prostate. In adult rats DFMO decreases the weight and RNA content of the ventral prostate within 4 days by 32% and 24% respectively and maintains them constant for the next 19 days. After 23 days of treatment, the prostatic weight is 46% of that of control animals of the same age, whereas the weights of other organs are only slightly decreased. Cytological studies carried out at this time show that DFMO reduces the size of both prostatic acini and the epithelial cells lining the acini.

scholarly journals S-Adenosylmethionine metabolism and its relation to polyamine synthesis in rat liver. Effect of nutritional state, adrenal function, some drugs and partial hepatectomy

1977 ◽  
Vol 168 (2) ◽  
pp. 179-185 ◽  
Author(s):  
Terho O. Eloranta ◽  
Aarne M. Raina
Keyword(s):  
Rat Liver ◽  
Hepatic Metabolism ◽  
Adrenal Function ◽  
Nutritional State ◽  
Polyamine Metabolism ◽  
Experimental Conditions ◽  
Deficient Diet ◽  
Polyamine Synthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Nutritional Conditions

S-Adenosylmethionine metabolism and its relation to the synthesis and accumulation of polyamines was studied in rat liver under various nutritional conditions, in adrenalectomized or partially hepatectomized animals and after treatment with cortisol, thioacetamide or methylglyoxal bis(guanylhydrazone) {1,1′-[(methylethanediylidine)dinitrilo]diguanidine}. Starvation for 2 days only slightly affected S-adenosylmethionine metabolism. The ratio of spermidine/spermine decreased markedly, but the concentration of total polyamines did not change significantly. The activity of S-adenosylmethionine decarboxylase initially decreased and then increased during prolonged starvation. This increase was dependent on intact adrenals. Re-feeding of starved animals caused a rapid but transient stimulation of polyamine synthesis and also increased the concentrations of S-adenosylmethionine and S-adenosylhomocysteine. Similarly, cortisol treatment enhanced the synthesis of polyamines, S-adenosylmethionine and S-adenosylhomocysteine. Feeding with a methionine-deficient diet for 7–14 days profoundly increased the concentration of spermidine, whereas the concentrations of total polyamines and of S-adenosylmethionine showed no significant changes. The results show that nutritional state and adrenal function play a significant role in the regulation of hepatic metabolism of S-adenosylmethionine and polyamines. They further indicate that under a variety of physiological and experimental conditions the concentrations of S-adenosylmethionine and of total polyamines remain fairly constant and that changes in polyamine metabolism are not primarily connected with changes in the accumulation of S-adenosylmethionine or S-adenosylhomocysteine.

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