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.

THE 5β-METABOLITES OF TESTOSTERONE: MODE AND SEX-SPECIFICITY OF THEIR FORMATION IN THE RAT LIVER

1973 ◽  
Vol 73 (3) ◽  
pp. 577-584 ◽  
Author(s):  
Rüdiger Ghraf ◽  
Hanns-Georg Hoff ◽  
Edmund Rodney Lax ◽  
Herbert Schriefers
Keyword(s):  
Rat Liver ◽  
Formation Rate ◽  
Hepatic Metabolism ◽  
Male Rats ◽  
Test Model ◽  
Experimental Conditions ◽  
Liver Slices ◽  
Male Animal ◽  
Sex Specificity ◽  
Direct Hydrogenation

ABSTRACT Rat liver slices provide a suitable test model which, with simple and variable experimental conditions, contributes direct evidence for the formation of the 5β-metabolites, 17β-hydroxy-5β-androstan-3-one, 5β-androstane-3α,17β-diol and 3α-hydroxy-5β-androstan-17-one, from a direct hydrogenation of testosterone glucuronide. When liver slices are incubated with testosterone in a KHR-phosphate medium no glucuronidation occurs and no 5β-metabolites are formed. They are produced, however, in a KHR-hydrogencarbonate medium, in which the slices are able to form glucuronides. Moreover, the production rate of 5β-hydrogenated products like that of testosterone glucuronide formation is sex-specific. The male animal metabolizes less testosterone by oxidoreductive pathways than the female and thus exhibits the higher testosterone glucuronide formation. This higher glucuronide formation rate is closely associated with the appearance of 5β-metabolites in the aglucone fraction. Apparently, the testosterone glucuronide formation rate of the female animal is not sufficiently high to allow the production of 5β-configurated C19O2-aglucones in measurable quantities. An experimentally induced feminization of the hepatic metabolism of genetically male rats by a single injection of 300 μg oestradiol benzoate on day 2 of life reduces the testosterone glucuronide formation rate to the female level and causes the 5β-metabolites to disappear. Thus, it is evident that at least those 5β-metabolites mentioned above are products of a direct hydrogenation of testosterone glucuronide.

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 Effect of methylglyoxal bis(guanylhydrazone) on polyamine metabolism in normal and regenerating rat liver and rat thymus

1973 ◽  
Vol 136 (3) ◽  
pp. 669-676 ◽  
Author(s):  
E. Hölttä ◽  
P. Hannonen ◽  
J. Pispa ◽  
J. Jänne
Keyword(s):  
Rat Liver ◽  
Diamine Oxidase ◽  
Competitive Inhibitor ◽  
Polyamine Metabolism ◽  
Adenosylmethionine Decarboxylase ◽  
Regenerating Rat Liver ◽  
Marked Accumulation ◽  
Sublethal Doses ◽  
Oxidase Reaction

1. Injections of sublethal doses of methylglyoxal bis(guanylhydrazone), a potent inhibitor of putrescine-activated S-adenosylmethionine decarboxylase in vitro, resulted after a few days in an immense increase in the activity of S-adenosylmethionine decarboxylase in normal and regenerating rat liver and in rat thymus. The increase in the activity of S-adenosylmethionine decarboxylase was at least partly due to a marked lengthening of the half-life of the enzyme. 2. In regenerating liver and thymus there was also a moderate stimulation of the activity of ornithine decarboxylase (EC 4.1.1.17) and a marked accumulation of tissue putrescine. 3. Injection of methylglyoxal bis(guanylhydrazone) into the rat also markedly decreased the activity of diamine oxidase (EC 1.4.3.6) in thymus. 4. In no cases where doses of methylglyoxal bis(guanylhydrazone) close to the LD50 dose for the rat were used was it possible to lower tissue spermidine content to any significant extent. 5. Methylglyoxal bis(guanylhydrazone) seemed to act as a competitive inhibitor for the substrate S-adenosylmethionine and as an uncompetitive inhibitor for the activator putrescine in the decarboxylation of S-adenosylmethionine in vitro. 6. In the diamine oxidase reaction, with putrescine as the substrate, methylglyoxal bis(guanylhydrazone) was a non-competitive inhibitor for putrescine.

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 of spermidine formation in rat liver and kidney by methylglyoxal bis(guanylhydrazone)

1973 ◽  
Vol 132 (3) ◽  
pp. 537-540 ◽  
Author(s):  
A. E. Pegg
Keyword(s):  
Rat Liver ◽  
Intraperitoneal Injection ◽  
Essential Role ◽  
Complete Inhibition ◽  
Polyamine Metabolism ◽  
Polyamine Synthesis ◽  
Liver And Kidney

The effect of methylglyoxal bis(guanylhydrazone), a substance known to inhibit putrescine-dependent S-adenosyl-l-methionine decarboxylase, on polyamine metabolism in liver and kidney was investigated. Almost complete inhibition of the incorporation of putrescine into spermidine was obtained up to 8h after administration of 80mg of methylglyoxal bis(guanylhydrazone)/kg body wt. by intraperitoneal injection. However, by 20h after administration of the inhibitor spermidine synthesis was resumed. Considerable accumulation of putrescine occurred during this period (up to 3 times control concentrations in both tissues), but there was only a slight fall in the spermidine content. These results suggest that the putrescine-activated S-adenosyl-l-methionine decarboxylase plays an essential role in spermidine biosynthesis in rat liver and kidney, and the possibility of using methylglyoxal bis(guanylhydrazone) to study the role of polyamine synthesis in growth is discussed.

Effect of l,3-diaminopropan-2-o1, an inhibitor of ornithine decarboxylase, on the metabolic response of liver to insulin

1982 ◽  
Vol 60 (12) ◽  
pp. 1493-1498 ◽  
Author(s):  
Yu-Wan Hu ◽  
Douglas E. Hall ◽  
Margaret E. Brosnan
Keyword(s):  
Ornithine Decarboxylase ◽  
Glycogen Content ◽  
Metabolic Response ◽  
Diabetic Rats ◽  
Polyamine Metabolism ◽  
Polyamine Synthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Streptozotocin Diabetic Rats

The effect of diaminopropanol, an inhibitor of polyamine synthesis, on the metabolic response of liver to insulin was studied in streptozotocin-diabetic rats. Insulin elicited a prompt and very marked increase in ornithine and S-adenosylmethionine decarboxylase activities and in putrescine concentration. Pretreatment of rats with diaminopropanol prevented the increase in the decarboxylases and resulted in decreased spermidine and spermine content of liver. The insulin-induced increase in glycogen content was depressed by 50% and the increase in the rate of lipogenesis in vivo was completely prevented by prior injection of diaminopropanol. These studies implicate altered polyamine metabolism in the metabolic response of liver of streptozotocin-diabetic rats to insulin.

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 Inhibition of S-adenosylmethionine decarboxylase by inhibitor SAM486A connects polyamine metabolism with p53-Mdm2-Akt/protein kinase B regulation and apoptosis in neuroblastoma

2009 ◽  
Vol 8 (7) ◽  
pp. 2067-2075 ◽  
Author(s):  
Dana-Lynn T. Koomoa ◽  
Tamas Borsics ◽  
David J. Feith ◽  
Craig C. Coleman ◽  
Christopher J. Wallick ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase B ◽  
Polyamine Metabolism ◽  
Adenosylmethionine Decarboxylase

scholarly journals Albumin binding of unconjugated [3H]bilirubin and its uptake by rat liver basolateral plasma membrane vesicles

1996 ◽  
Vol 316 (3) ◽  
pp. 999-1004 ◽  
Author(s):  
Lorella PASCOLO ◽  
Savino DEL VECCHIO ◽  
Ronald K. KOEHLER ◽  
J. Enrique BAYON ◽  
Cecile C. WEBSTER ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Rat Liver ◽  
Basolateral Membrane ◽  
Membrane Vesicles ◽  
Plasma Membrane Vesicles ◽  
Experimental Conditions ◽  
Saturation Kinetics ◽  
Basolateral Plasma Membrane ◽  
Component C ◽  
Uptake Studies

Using highly purified unconjugated [3H]bilirubin (UCB), we measured UCB binding to delipidated human serum albumin (HSA) and its uptake by basolateral rat liver plasma membrane vesicles, in both the absence and presence of an inside-positive membrane potential. Free UCB concentrations ([Bf]) were calculated from UCB–HSA affinity constants (K´f), determined by five cycles of ultrafiltration through a Centricon-10 device (Amicon) of the same solutions used in the uptake studies. At HSA concentrations from 12 to 380 μM, K´f (litre/mol) was inversely related to [HSA], irrespective of the [Bt]/[HSA] ratio. K´f was 2.066×106+(3.258×108/[HSA]). When 50 mM KCl was iso-osmotically substituted for sucrose, the K´f value was significantly lower {2.077×106+(1.099×108/[HSA])}. The transport occurred into an osmotic-sensitive space. Below saturation ([Bf] ⩽ 65 nM), both electroneutral and electrogenic components followed saturation kinetics with respect to [Bf], with Km values of 28±7 and 57±8 nM respectively (mean±S.D., n = 3, P < 0.001). The Vmax was greater for the electrogenic than for the electroneutral component (112±12 versus 45±4 pmol of UCB·mg-1 of protein·15 s-1, P < 0.001). Sulphobromophthalein trans-stimulated both electrogenic (61%) and electroneutral (72%) UCB uptake. These data indicate that: (a) as [HSA] increases, K´f decreases, thus increasing the concentration of free UCB. This may account for much of the enhanced hepatocytic uptake of organic anions observed with increasing [HSA]. (b) UCB is taken up at the basolateral membrane of the hepatocyte by two systems with Km values within the range of physiological free UCB levels in plasma. The electrogenic component shows a lower affinity and a higher capacity than the electroneutral component. (c) It is important to calculate the actual [Bf] using a K´f value determined under the same experimental conditions (medium and [HSA]) used for the uptake studies.

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