Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.1.17 (ornithine decarboxylase)
6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatic levels of 5'-deoxy-5'-methylthioadenosine (MTA) were measured in the livers of adult male Sprague-Dawley rats a) killed at various times during the liver regeneration process, b) killed at times after partial hepatectomy when the liver mass had already been completely restored (hereafter called post-regeneration livers), or c) continuously fed 3'-methyl-4-dimethyl-aminoazobenzene (CAS: 55-80-1) up to the full development of hepatoma and killed at regular intervals during hepatocarcinogenesis. Hepatic MTA levels were always significantly decreased, although to different degrees in both in vivo models of hepatic growth and at all times during the investigation. Astonishingly, the MTA levels were also significantly decreased in the post-regeneration livers, in which there was also a significant increase in the activity of adenosylmethionine decarboxylase (S-adenosyl-L-methionine decarboxylase; EC 4.1.1.50) with normal levels of activity of ornithine decarboxylase (EC 4.1.1.17). These results demonstrate that a) the MTA content is always decreased in rat liver whenever this organ is involved in a proliferative process (whether controlled or uncontrolled); b) the decrease in hepatic MTA content is a biochemical feature necessary for, but by no means by itself sufficient for, hepatocyte proliferation to occur, since this decrease remains long after complete restoration of the liver mass; and c) the return of the hepatocytes to the normal biochemical program after restoration of the liver mass is not complete, even though these cells become quiescent, because there are still some biochemical abnormalities in the post-regeneration livers.
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PMID:Persistently decreased hepatic levels of 5'-deoxy-5'-methylthioadenosine during regeneration of and chemical carcinogenesis in rat liver. 345 57

1-Aminooxy-3-aminopropane (APA) was shown to be a potent competitive inhibitor (Ki = 1.0 nM) of partially purified Escherichia coli ornithine decarboxylase. APA did not inhibit S-adenosyl-L-methionine decarboxylase and spermidine from E. coli. S-(5'-Deoxy-5'-adenosyl)methylthioethylhydroxylamine (AMA), which is a structural analogue of decarboxylated S-adenosyl-L-methionine, was for the first time shown to be an irreversible inhibitor of bacterial S-adenosyl-L-methionine decarboxylase and a competitive inhibitor (Ki = 47 microM) of bacterial ornithine decarboxylase. AMA had no effect on spermidine synthase.
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PMID:The effects of 1-aminooxy-3-aminopropane and S-(5'-deoxy-5'-adenosyl)methylthioethylhydroxylamine on ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase from Escherichia coli. 352 75

Ornithine decarboxylase (ODC), S-adenosyl-L-methionine decarboxylase (AMDC) and arginine decarboxylase (ADC) activities were detected for the first time in extracts of Mycobacterium bovis (BCG). All the decarboxylases differed from corresponding known bacterial decarboxylases in that: a) ODC did not require GTP for activity; b) ODC was not inhibited by any known inhibitor of bacterial ODCs; c) AMDC and ADC did not require Mg2+-ion for activity and were not markedly inhibited by any known inhibitor of the decarboxylases of other bacteria.
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PMID:Ornithine decarboxylase, S-adenosyl-L-methionine decarboxylase and arginine decarboxylase from Mycobacterium bovis (BCG). 354 91

The levels of polyamines and their synthesizing enzymes in squamous cell carcinoma of prostate implanted in intact as well as castrated male rats were determined after certain hormonal manipulations. The tumour was found to grow with an identical rate in non-castrated and castrated rats. Polyamine content and activities of polyamine synthesizing enzymes in the tumour were found to be much lower compared to their values in ventral prostate. Moreover, the levels of these parameters were comparable in tumours whether implanted in non-castrated or gonadectomized animals. The sequential analyses of putrescine and spermidine and activities of L-ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase of tumours at different time intervals showed a significant reduction in their levels at 30 days compared to 10 days post implantation in non-castrated as well as castrated rats. Daily intramuscular administration of tumour-bearing intact or castrated animals with testosterone (50 micrograms/g), beta-estradiol (2 micrograms/g) or cyproterone (12.5 micrograms/g) for 10 days did not influence polyamine metabolism in tumour tissue. However, either beta-estradiol and cyproterone treatments or castration were found to decrease polyamine synthesis in ventral prostate. At the same time, the testosterone replacement therapy did not allow polyamine levels or activities of polyamine synthesizing enzymes to decline in the ventral prostate of castrated rats. Our results demonstrated that contrary to ventral prostate, the polyamine metabolism in squamous cell carcinoma of prostate is independent of hormonal control. The loss of hormonal sensitivity of polyamine metabolism in the prostatic tumour could be the result of qualitative changes that occurred during transformation.
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PMID:Hormone-independent polyamine metabolism of squamous cell carcinoma of the prostate. 383 20

Although ornithine decarboxylase under most conditions is the rate-controlling enzyme of polyamine biosynthesis and thus the most logical target for chemical intervention, the inhibition of the enzyme triggers a series of compensatory reactions all aimed to circumvent the inhibition. These include secondary induction of adenosylmethionine decarboxylase, enhanced accumulation of extracellular polyamines and an overproduction of ornithine decarboxylase resulting from enhanced expression and gene amplification. Thus chemotherapy based on an intervention of polyamine formation has also to be directed to reactions other than the decarboxylation of ornithine. Adenosylmethionine decarboxylase is the second natural target for chemotherapy. Virtually all effective inhibitors of this enzyme are members of the family of bis(guanylhydrazones). Small modifications, such as increased hydrophobicity at the glyoxal portion of the parent compound glyoxal bis(guanylhydrazone), greatly enhance the inhibition of adenosylmethionine decarboxylase and diminish the undesirable inhibition of diamine oxidase. However, although ethylglyoxal and propylglyoxal bis(guanylhydrazone) appear to utilize the putative polyamine carrier for their cellular entry, their cellular accumulation, in contrast to that of glyoxal and methylglyoxal bis(guanylhydrazone), is not stimulated by putrescine and spermidine deprivation produced by inhibitors of ornithine decarboxylase. It is obvious that the cellular accumulation of each of the bis(guanylhydrazones) is determined by their different efflux rates: GBG and MGBG are effectively retained whereas EGBG is rapidly excreted by the tumor cells. GBG and MGBG, but possibly not EGBG, behave as mitochondrial poisons and rapidly produce extensive morphological damage of the mitochondria. The bis(guanylhydrazones) likewise inhibit carnitine-dependent mitochondrial oxidation of long-chain fatty acids, competitively in respect to carnitine. It is possible that this inhibition has something to do with the mitochondrial damage, as carnitine protects tumor cells from the early mitochondrial damage produced by MGBG. Carnitine also protects experimental animals from MGBG-induced acute toxicity and death.
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PMID:S-adenosylmethionine decarboxylase as target of chemotherapy. 393 95

Chinese hamster cells (line CHO) maintained in McCoy's 5A medium (modified) supplemented with insulin (10 micrograms/ml), transferrin (5 micrograms/ml), and ferrous sulfate (1.1 microgram/ml) proliferate at rates similar to cultures growing in the McCoy's medium supplemented with 10% fetal bovine serum. Colony-forming ability is similar in cultures supplemented with either serum or the combination of growth factors. By 6 hours after replacement of serum with growth factors, ornithine decarboxylase (ODCase) activity increases, reaching a maximum value by 24 hours after serum replacement. This maximum is cell density dependent and can exceed a 30-fold increase over enzyme activity in cultures supplemented with serum. The increased enzyme activity is due to a decrease in the turnover rate of the enzyme, based on protein synthesis inhibition studies, and an accumulation of active enzyme molecules rather than an activation of existing molecules, since the catalytic activity of ODCase, determined using the radiolabeled form of alpha-difluoromethylornithine (an enzyme-activated, irreversible inhibitor of ODCase) in concert with supplements. Intracellular putrescine and spermidine levels are substantially decreased when cultures are maintained in medium supplemented with insulin, transferrin, and ferrous sulfate, rather than serum, which is the sole source of exogenous ornithine. Titration of cultures growing in the defined medium with ornithine leads to a decrease in ODCase activity and an increase in intracellular putrescine and spermidine levels. Putrescine- and spermidine-dependent S-adenosyl-L-methionine decarboxylase activities are similar in cultures maintained in either medium. These data demonstrate that some, but not all, aspects of polyamine biosynthesis are affected by the availability of ornithine, the first substrate in the pathway.
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PMID:Altered polyamine metabolism in Chinese hamster cells growing in a defined medium. 395 58

We have measured the activities of the two rate controlling enzymes in polyamine synthesis, L-ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (SAMDC), and the concentrations of the polyamines, putrescine, spermidine and spermine, in the developing chick embryo from laying to hatching. The embryo exhibited major peaks in the ODC and SAMDC activities as well as in the concentrations of all three polyamines at 15 h (gastrulation), 23-30 h (early organogenesis), days 4-5 (mid-organogenesis), and days 12-17 (organ growth and maturation). In the 4 and a half-day-old embryo, ODC activity and polyamine concentrations were about twice as high in the head region as compared to the trunk region. In the 14-day-old embryo, the highest ODC and SAMDC activities were found in lung, intestine and kidney, and there was a positive correlation between the enzyme activities and the growth rates of most organs/tissues.
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PMID:Changes in polyamine synthesis and concentrations during chick embryo development. 405 78

We have determined the levels of L-ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (AMD) in 134 untreated human primary tumors, such as skin epitheliomas and brain tumors. The levels of both decarboxylases increase in proportion to the grade of malignancy (ascertained by histologic criteria) in both the basal cell and squamous cell carcinomas of the skin. In the various types of brain tumors, ODC levels are more reliable indications of the grade of malignancy than AMD levels. In fact, the highest ODC levels observed in medulloblastoma and in astrocytoma grade IV were not associated with similarly high AMD levels. The same dichotomy between the levels of the two decarboxylases was observed for meningiomas, in which ODC levels were higher in atypical forms (with karyokinesis) then in typical forms (without karyokinesis).
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PMID:Degree of enhancement of polyamine biosynthetic decarboxylase activities in human tumors: a useful new index of degree of malignancy. 406 29

Ornithine decarboxylase (EC 4.1.1.17), the enzyme that catalyzes the synthesis of putrescine from ornithine, increases dramatically in developing Xenopus embryos. Between the 2-cell stage and early blastula stage, activity increases 10-fold, and in swimming tadpoles, the enzyme activity is 100-fold higher than that present in either unfertilized eggs or 2-cell embryos. S-adenosyl-L-methionine decarboxylase, an enzyme that catalyzes spermidine synthesis from putrescine and S-adenosyl-L-methionine, increases 40-fold in activity during the development of Xenopus, but does not increase in activity prior to gastrulation. Concomitant with these enzyme changes, putrescine and spermidine concentrations are elevated during the development of Xenopus embryos. Maximal accumulations are present in the swimming tadpole and correspond to maximal enzyme activities. Anucleolate-mutant embryos of Xenopus, which do not synthesize new ribosomes, have no detectable S-adenosyl-L-methionine decarboxylase activity and do not accumulate spermidine after gastrulation. Ornithine decarboxylase activity is depressed in these mutants and putrescine accumulation is decreased also. The activity of some dehydrogenases that increase in Xenopus embryos after gastrulation show normal increases in the anucleolate mutants. Thus, the synthesis of putrescine and spermidine in embryos correlates with the onset of ribosomal-RNA synthesis and the formation of a viable nucleolus in the embryonic cell.
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PMID:Putrescine and spermidine biosynthesis in the development of normal and anucleolate mutants of Xenopus laevis. 527 54

Polyamine biosynthesis and arginase activity in psoriasis were studied using keratotome strips and suction blister roofs as specimens. In the uninvolved psoriatic skin a slight (1.3-fold; p less than 0.05) increase in the spermidine level was observed compared with control skin. There was also a 1.2-fold increase (p less than 0.05) in the spermidine/spermine molar ratio, which is considered to be an indicator of proliferation activity. No changes were noted in other polyamines or polyamine-synthesizing enzymes ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (AMDC) in the uninvolved psoriatic skin vs. control skin. Neither was there any significant difference in the arginase activity. In psoriatic lesions the levels of all polyamines, as well as the activities of biosynthetic enzymes, were significantly (p less than 0.001) elevated. The putrescine level was elevated to 2.5-fold, spermidine to 2.7-fold and spermine to 1.4-fold. The enzyme activities expressed severalfold increases. The enhancement of arginase activity was less prominent than that of polyamine-synthesizing enzymes, but the increase from 271 +/- 88 to 354 +/- 126 mumol/g/h (1.3-fold) was statistically significant (p less than 0.001; paired t-test). The increase in arginase activity in suction blister roofs, which represents pure epidermis, was more pronounced than that in keratotome strips, i.e. about double. The results show thus that polyamine biosynthesis is significantly enhanced in psoriatic lesions, but there is only a slight difference between the uninvolved psoriatic skin and control skin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arginase activity and polyamine biosynthesis in psoriasis. 619 57


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