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At least 19 recordsLinked to original sources

PubMed1978

Increase of urinary putrescine in 3,4-benzopyrene carcinogenesis and its inhibition by putrescine.

A significant increase in putrescine was noted in the urine of mice with experimental s.c. tumors induced by a single injection of 3,4-benzopyrene solution (2.52 mg of 3,4-benzopyrene in 0.5 ml of tricaprylin). When 10 mg of putrescine were added to the 3,4-benzopyrene solution, the development of tumors was completely inhibited and the increase of urinary putrescine in mice was suppressed simultaneously. Animal weight data of a control group receiving only putrescine indicated that the inhibitory effect of putrescine is not due to its toxicity.

Animals↗

PubMed1976

Mechanism of action of putrescine oxidase. Binding characteristics of the active site of putrescine oxidase from Micrococcus rubens.

Putrescine oxidase (EC 1.4.3.4), putrescine: oxygen oxidoreductase (deaminating) (flavin containing), has been found to form complexes with a variety of amines. With few exceptions these compounds competitively inhibit putrescine oxidation and also perturb the visible absorption spectrum of the enzyme (i.e., the spectrum due to FAD). Inhibition constants are reported for a number of amines; the presence of a cationic amino group in the inhibitors appears to be the structural feature essential for competitive inhibition. Inhibition constants for amino acids are larger than those for the analogous simple amines and the inhibition constants for alkyl mono- and diamines in a homologous series are inversely related to the length of the hydrocarbon chain. Amines containing unsaturated and aromatic substituents yield relatively low inhibition constants. The spectral changes observed upon complex formation are interpreted as indicating a less polar environment for FAD in the enzyme-inhibitor complex than in the uncomplexed enzyme. On the basis of the enzyme's substrate specificity and comparisons among inhibitor structures and the corresponding inhibition constants, a schematic model of the enzyme's active site is proposed.

Amines↗

PubMed1976

Putrescine transport is greatly increased in human fibroblasts initiated to proliferate.

Putrescine (diaminobutane) was previously found to stimulate proliferation of human fibroblasts in tissue culture, and a growth factor produced by these cells was identified as putrescine. In the present paper putrescine transport is studied. The rate of putrescine transport was dependent on temperature, and most of the labeled putrescine was retained by the cells after washing with excess unlabeled putrescine. The concentration of radioactivity after a [14 C]putrescine pulse was 85 times higher in the cells than in the medium, and over 95% of the radioactivity in the cells was as unchanged putrescine. Butanol treatment removed 70% of the radioactivity from the cells. The calculated Km was about the same for rapidly growing and for starved cultures, while Vmax was higher for the former than for the latter cultures. Putrescine transport was inhibited to varying degrees by other polyamines, but not by amino acids or divalent cations. Stimulation of cell proliferation by serum was followed by an 18-100-fold increase in the rate of putrescine transport, which was not inhibitable with cyclic AMP, dibutyryl cyclic AMP, or prostaglandin E1. Removal of serum resulted in a rapid decrease in the rate of putrescine transport. Insulin in low serum medium and trypsin in the absence of serum also accelerated putrescine transport. Moreover, the rate of putrescine transport was dependent on cell density. It was faster in sparsely populated than in densely populated cultures. SV40-transformed human fibroblasts responded to addition and removal of serum in the same way as the untransformed parent cell line.

Biological Transport↗

PubMed1979

Putrescine uptake by the cellular slime mould dictyostelium discoideum.

1. Rapid labelling occurs when myxamoebae of Dictyostelium discoideum strain AX2 are incubated with [1,4-14C]putrescine. Labelling is energy-dependent. 2. The label enters a pool from which rapid exchange with extracellular putrescine does not occur, and labelling is believed to represent uptake into the cells. 3. The concentration-dependence of putrescine uptake indicates that a number of systems are involved, at least one of which is saturable, with a Km of 9.1 micro M-putrescine. At high putrescine concentrations the overall uptake process is non-saturable. 4. Significant metabolism of putrescine and loss of intracellular putrescine to the medium only occurred when cells were incubated with millimolar concentrations of extracellular putrescine. 5. Putrescine uptake was inhibited by diamines, polyamines, bivalent metal ions and omega-aminocarboxylic acids. 6. The ability to take up putrescine at low concentrations decreased during starvation of myxamoebae. 7. The results are interpreted in terms of a model for putrescine uptake involving adsorptive pinocytosis at low concentrations and fluid-phase pinocytosis at high concentrations.

Carboxylic Acids↗

PubMed1979

Putrescine-oxidase activity in adult bovine serum and fetal bovine serum.

Putrescine-oxidase activity was found in fetal bovine serum (FBS) with a pH optimum of 8.0 and in adult bovine serum (ABS) with a pH optimum of 9.8. The crude FBS enzyme had a KM for putrescine of 2.58 x 10(-6) M and a Vmax of 0.53 nmol per hr per 50 microliter serum. Aminoguanidine competitively inhibited the enzyme with a KI of 1.8 x 10(-8) M. Spermidine and spermine proved competitive inhibitors of putrescine for both the FBS and the crude ABS putrescine oxidases. The Vmax for the ABS putrescine oxidase was 2.10 nmol per hr per 50 microliter serum, and the KM for putrescine, 50.3 x 10(-6) M. The K1 of the ABS putrescine oxidase for aminoguanidine was 41 x 10(-6) M. On the basis of both the KM and KI values, the adult serum enzyme, at its optimal pH of 9.8, bound spermidine and spermine more avidly than the smaller putrescine and aminoguanidine; whereas the FBS enzyme, at pH 8.0, bound aminoguanidine and putrescine more tightly than the larger polyamines. Each of the enzymes retained over 80% of its activity after heating at 56 degrees C for 30 min. Applications of these data to the study of polyamines in tissue culture and to the purification of diamine oxidases are discussed.

Animals↗

PubMed1975

4-aminobutyrate in mammalian putrescine catabolism.

The effects of inhibitors of diamine oxidase (EC 1.4.3.6), monoamine oxidase (EC 1.4.3.4) and 4-aminobutyrate aminotransferase (EC 2.6.1.19) on the catabolism of putrescine in mice in vivo were studied. Diamine oxidase inhibitors and carboxymethoxylamine (amino-oxyacetate) markedly inhibit the metabolism of [(14)C]putrescine to (14)CO(2), but affect different enzymes. Aminoguanidine specifically inhibits the mitochondrial and non-mitochondrial diamine oxidases, whereas carboxymethoxylamine specifically inhibits 4-aminobutyrate transamination by the mitochondrial pathway. Hydrazine inhibits at both sites, and results in increased concentrations of 4-aminobutyrate in brain and liver. Pretreatment of mice with carboxymethoxylamine and [(14)C]putrescine leads to the urinary excretion of amino[(14)C]butyrate. Carboxymethoxylamine does not affect the non-mitochondrial pathway of putrescine catabolism, as the product of oxidative deamination of putrescine in the extramitochondrial compartment is not further oxidized but is excreted in the urine as derivatives of 4-aminobutyraldehyde. Another catabolic pathway of putrescine involves monoamine oxidase, and the monoamine oxidase inhibitor, pargyline, decreases the metabolism of [(14)C]putrescine to (14)CO(2)in vivo. Catabolism of putrescine to CO(2)in vivo occurs along different pathways, both of which have 4-aminobutyrate as a common intermediate, in contrast with the non-mitochondrial catabolism of putrescine, which terminates in the excretion of 4-aminobutyraldehyde derivatives. The significance of the different pathways is discussed.

4-Aminobutyrate Transaminase↗

PubMed1979

Uptake and accumulation of putrescine and its lethality in Anacystis nidulans.

The rate of uptake of putrescine by Anacystis nidulans has been shown to depend on the external pH and the extracellular concentration of putrescine. Accumulation of exogenous putrescine was also proportional to the concentration of putrescine in the medium, suggesting that putrescine uptake was not subject to cellular regulation. An equation was derived to test the hypothesis that putrescine accumulation was due to ion trapping. Comparison of the predicted and observed intracellular concentrations of putrescine under various conditions showed a close correlation in support of the hypothesis of ion trapping. Under conditions leading to cell death (e.g., 150 microM putrescine, pH 9.8), the correlation did not hold as a result of leakage of accumulated putrescine.

Cyanobacteria↗

PubMed1979

Structure and properties of the putrescine carbamoyltransferase of Streptococcus faecalis.

Ornithine and putrescine carbamoyltransferases from Streptococcus faecalis ATCC11700 have been purified and their structural properties compared. The molecular weight of native ornithine carbamoyltransferase, measured by molecular sieving, is 250 000. It is composed of six apparently identical subunits with a molecular weight of 39 000, as determined by cross-linking with the bifunctional reagent glutaraldehyde followed by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate. Using the same method, putrescine carbamoyltransferase is a trimer of 140 000 consisting of three identical subunits with a molecular weight of 40 000. Ornithine carbamoyltransferase displays a narrow specificity towards its substrate, ornithine. In contrast, putrescine carbamoyltransferase carbamoylates ornithine and several diamines (diaminopropane, diaminohexane, spermine, spermidine, cadaverine) in addition to its preferred substrate, putrescine, but with a considerable lower efficiency than for putrescine. The kinetic mechanism of putrescine carbamoyltransferase has been investigated. Initial velocity studies yield intersecting plots using either putrescine or ornithine as substrate, indicating a sequential mechanism. The patterns of protection of the enzyme by the reactants during heat inactivation as well as the results of product and dead-end inhibition studies provide evidence for a random addition of the substrates. The putrescine inhibition that is induced by phosphate does, however, suggest that a preferred pathway exists in which carbamoylphosphate is the leading substrate. The different kinetic constants have been established. The properties of putrescine carbamoyltransferase are compared to the known properties of other carbamoyltransferases. The evolutionary implications of this comparison are discussed.

Carboxyl and Carbamoyl Transferases↗

PubMed1979

Effects of L-dopa on putrescine levels in the brain and the liver of the rat.

The pharmacological effects of several amino acid precursors of putative neurotransmitters on putrescine levels in the brain and the liver of the rat were studied. L-dopa increased brain and liver putrescine levels in a dose-dependent manner that reached its maximum effect in 4-6 h. The increase in liver putrescine was associated with a concomitant increase in ornithine decarboxylase activity. L-5-hydroxytryptophan increased liver putrescine but had no effect on brain putrescine levels. D-DOPA and D-5-hydroxytryptophan were both ineffective in altering brain or liver putrescine. The effects of L-DOPA persisted after hypophysectomy and were not associated with changes in tissue levels of S-adenosylmethionine. The repeated administration of L-DOPA for periods of 48 and 96 h resulted in a sustained elevation of putrescine levels in the brain but not in the liver.

Amino Acids↗

PubMed1977

Antagonistic action between spermidine and putrescine on association and dissociation of purified, run-off ribosomes from Escherichia coli.

The effects of polyamines on the equilibrium between prokaryotic ribosomal subunits and 70 S ribosomes have been studied as a function of concentration of Mg2+ from 2.5 to 7.5 mM. Run-off ribosomes were obtained from Escherichia coli and were washed with buffered 1 M NH4C1. Spermidine at 1 mm favors association of subunits at all concentrations of Mg2+. Putrescine, at concentrations above 8 mM, favors net dissociation at concentrations of Mg2+ below 4.5 mM. Streptomycin behaves like spermidine, while putrescine behaves like initiation factor 1 and initiation factor 3. The effect of putrescine on dissociation is time-dependent and appears to have a half-life of about 3.5 min at 30 degrees. When added after the effects of spermidine or streptomycin on association have occurred, putrescine still causes dissociation. The data suggests that putrescine may reduce net formation of vacant 70 S ribosomes. Another possibility is that putrescine and spermidine may act antagonistically to maintain a labile equilibrium between ribosomal subunits and vacant 70 S ribosomes. It may be significant that the putrescine effect is observed at the concentration of Mg2+ found to be optimum for initiation.

Escherichia coli↗

PubMed1979

Mechanism of toxicity of putrescine in Anacystis nidulans.

Putrescine is lethal to the cyanobacterium Anacystis nidulans at extracellular pH values at which significant concentrations of the nonprotonated diamine rapidly diffuse into the cell and accumulate as the charged form. Although over 98% of the accumulated putrescine is not metabolized, a small fraction is rendered trichloroacetic acid-insoluble, and about 90% of this is bound as putrescinie to proteins and cell structures. Various synthetic functions were studied in the presence of a bacteriostatic (40 microM) and a bacteriocidal (150 microM) concentration of putrescine at pH 9.5. Under lethal conditions, protein synthesis was completely inhibited after 45 min and CO2 fixation after 100 min, whereas nucleic acid synthesis was less affected. Spermidine was lost from the cell and its synthesis was arrested. These functions were much less inhibited at 40 microM putrescine. Ribosomes from putrescine-killed cells were found to be irreversibly dissociated into 30S and 50S subunits. Some putrescine (1-4 molecules) cosedimented with each subunit.

Biological Transport↗

PubMed1979

Putrescine as a biochemical marker of malignant brain tumors.

Putrescine, spermidine, and spermine levels were determined in normal brain and central nervous system-related tumor tissues obtained at operation from 50 patients. The biochemical data were correlated with morphological histopathological descriptions of the same tissues. There was little variation in putrescine levels in normal cerebral cortical tissue. Subcortical white matter had lower putrescine but higher spermidine content than those of the overlying cortex. Putrescine levels were elevated in all astrocytomas assayed, and the magnitude of this elevation was proportional to the malignancy of the tumor as determined by histopathological criteria. In contradistinction, putrescine content of "benign" tumors was generally equal to or lower than that of the normal cerebral cortex. Spermidine and spermine levels varied widely in the tumors assayed and did not correlate with criteria of malignancy. It is concluded that putrescine may be a good biochemical marker of malignancy in central nervous system-related tumors.

Astrocytoma↗

PubMed1978

Possible involvement of putrescine in nucleolar formation in early embryos.

Continuous treatment of developing eggs of the polychete Ophryotrocha labronica with alpha-methylornithine, which inhibits synthesis of putrescine, led to arrest of development at gastrulation. The present ultrastructural analysis suggests that the arrest of development is due to failure to form nuclei, and thus reveals a possible role for putrescine in nucleolar formation. Further support for this contention was provided by means of electron-microscopical autoradiography. It was found that newly synthesized putrescine, derived from administered 3H-ornithine, labeled the nucleoli intensely at the time of their normal appearance during gastrulation, the time at which the rate of endogenous putrescine synthesis is maximal. These observations have led to the conclusion that putrescine synthesis may be directly involved in formation of nucleoli.

Animals↗

PubMed1977

Metabolism of putrescine in the central nervous system.

The metabolism of putrescine in rat brain was studied systematically by the intraventricular injection of radioactive diamine. Putrescine injected into the brain was metabolized mainly to polyamines, spermidine, and spermine. A small portion of the radioactivity of putrescine was incorporated into gamma-glutamylputrescine, putreanine, gamma-aminobutyric acid, and homocarnosine. Comparison of the specific radioactivities of gamma-aminobutyric acid and homocarnosine after the injection of radioactive putrescine with those after the injection of radioactive glutamic acid indicated that there may be a metabolic pool of gamma-aminobutyric acid (putrescine-gamma-aminobutyric acid system) which is different from the glutamic acid-gamma-aminobutyric acid system and which is effectively used for synthesis of the dipeptide.

Animals↗

PubMed1976

The effect of nandrolone, an anabolic steroid on putrescine metabolism in the mouse.

1 The catabolism of injected 14 C-putrescine was studied in mice treated with nandrolone phenpropionate, an anabolic steroid. 2 The putrescine was rapidly metabolized; almost 50% of the injected radioactivity was recovered within 2 h as 14 CO2 in the expired air. 3 Considerable amounts of radioactive gamma-aminobutyric acid (GABA) and an unidentified compound were found in the kidney and in the urine in addition to radioactive putrescine, spermidine and spermine both in controls and nandrolone-treated mice. 4 Nandrolone elevated the concentration of endogenous putrescine in the kidney and urine, eightfold and twentyfold, respectively, and the concentrations of spermidine and spermine were also increased 5 after the injection of 14C-putrescine the incorporation of 14C into spermidine was significantly increased in the kidney of mice receiving nandrolone.

Animals↗

PubMed1975

Putrescine shortens the S-period in human fibroblasts.

Previous results have indicated that addition of putrescine to cultures of human fibroblasts stimulates cell proliferation. It is shown in the present paper that this is mainly due to a shorteining of the cell cycle. In the presence of added putrescine the cell cycle was 4 hours shorter than in the control. This result was obtained both from analyzing the fraction of labeled mitoses (FLM) curves and from counting the mitoses in synchronous cultures. The FLM curves further revealed that the shortening of the cell cycle was caused mainly by reduction in the length of the time required for DNA synthesis. It was about 30% shorter in the presence of added putrescine than in the control. The fact that addition of putrescine results in shortening of the S-period, and that this is to a great extent responsible for the increased rate of cell proliferation, distinguishes putrescine from other known growth factors.

Cells, Cultured↗

PubMed1979

Affinity chromatography of putrescine oxidase from Micrococcus rubens and spermidine dehydrogenase from Serratia marcescens.

Putrescine oxidase [EC 1.4.3.4], putrescine : oxygen oxidoreductase (deaminating) (flavin-containing), from Micrococcus rubens and spermidine dehydrogenase from Serratia marcescens were adsorbed on amine-Sepharose 4B in which one of the terminal amino groups of diamine or triamine was covalently bound to Sepharose 4B leaving the other terminal amino group(s) free. The affinities of these enzymes for the amine-Sepharose 4B increased on increasing the chain length of the methylene groups in the immobilized amines and fell upon addition of the substrate. The affinity of putrescine oxidase modified with 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide (EDC) was reduced in comparison with that of the native enzyme so far as 1,12-diaminododecane-Sepharose 4B was concerned. From these results, it can be concluded that the interactions between the enzyme and the amine-Sepharose result from specific affinities mediated through the active sites of the enzymes. It is suggested that spermidine dehydrogenase as well as putrescine oxidase has as anionic point and a hydrophobic region in the active site. On the basis of these results, the applicability of the enzyme affinities to purification procedures was examined. When partially purified enzymes were subjected to affinity chromatography, the following results were obtained. Putrescine oxidase gave a purification factor of 40-fold with about 100% recovery on a 1,12-diaminododecane-Sepharose column. In the case of spermidine dehydrogenase, the purification factor and recovery on a 1,8-diaminooctane-Sepharose column were about 1,200-fold and 86%, respectively. By introducing affinity chromatography as a purification step, each enzyme could be purified more simply and with higher recovery.

Chromatography, Affinity↗

PubMed1979

On the formation of gamma-aminobutyric acid from putrescine in brain.

Gamma-aminobutyric acid is not formed in significant amounts from putrescine by incubation with rat brain homogenates. However, it is formed if acetyl-CoA is added to the incubation medium. This is taken as further evidence for the existence of a metabolic pathway in mammalian brain which comprises acetylation of putrescine to monoacetyl putrescine and oxidative deamination of monoacetyl putrescine by MAO. Nerve cells and glia cells have comparable capacities for putrescine degradation along this pathway.

Acetyl Coenzyme A↗