共查询到20条相似文献,搜索用时 31 毫秒
1.
R E Catalán M P Castillón V G Corces C Avila 《Biochemical and biophysical research communications》1977,74(1):279-284
The cytochrome P-450 content of primary hepatocyte cultures was maintained at levels close to those found by using a defined medium containing testosterone, thyroxine, hydrocortisone, estradiol, glucagon, insulin, linoleic acid and oleic acid. Using these cultures, [14C]aflatoxin B1, a potent liver carcinogen, was metabolized primarily to water-soluble metabolites. In agreement with results, aflatoxin M1 was the only nonpolar metabolite detected. In addition, a significant portion of radioactivity was covalently bound to cell constituents. These results suggest that primary hepatocyte cultures may be a good model of the liver for studying the metabolism and mechanism of action of toxic chemicals. 相似文献
2.
Kei Sasaoka Tadashi Ogawa Hideaki Tsuji Noriko Bando 《Biochimica et Biophysica Acta (BBA)/General Subjects》1980,630(1):137-140
Agaricus bisporus contains novel aromatic compounds. By incubation of the mushroom with [G-14 C] shikimic acid, the radioactivity was incorporated into tyrosine, phenylalanine and several unidentified metabolites. The most radioactive metabolite in the stipe and the cap was identified as . The radioactivity was proved to be localized in the 4-hydroxyaniline moiety of this compound. 相似文献
3.
Phosphorylation of high mobility group proteins 14 and 17 by nuclear protein kinase NII in rat O6 glioma cells 总被引:1,自引:0,他引:1
J J Harrison R A Jungmann 《Biochemical and biophysical research communications》1982,108(3):1204-1209
High mobility group (HMG) proteins 14 and 17 of rat C6 glioma cells are phosphorylated on both serine and threonine. In HMG 14 about 60% of the total [32P]phosphate was identified as phosphoserine and 40% as phosphothreonine. In HMG 17, there was 88% phosphoserine and 12% phosphothreonine. Glioma cell nuclear protein kinase NII phosphorylates HMG 14 and 17 on serine as well as threonine and the relative percentages of [32P]phosphoamino acid are similar to those seen . Nuclear protein kinase NI and the type I and II cAMP-dependent protein kinases exhibit only minor phosphorylating activity towards HMG 14 and 17. We conclude that nuclear protein kinase NII is responsible for the phosphorylation of HMG 14 and 17 . 相似文献
4.
The distribution and metabolism of nitrosodibutylamine were studied in Sprague-Dawley rats. The results indicated that in addition to the liver, metabolism of the substance occurred in the nasal mucosa, the lung and the oesophagus. Metyrapone and diethyldithiocarbamate reduced the production of 14CO2 from nitrosodibutylamine by all these tissues. There was no indication of metabolic capacity in the urinary bladder or the kidney. The results fit with the assumption that tumours of the urinary tract are induced by metabolites reaching these tissues via the urine. Besides the liver, the oesophagus and the lung are target tissues for the carcinogenicity of N-nitrosodibutylamine in Sprague-Dawley rats and in these tissues the local formation of reactive metabolites may play a role in the pathogenesis of N-nitrosodibutylamine-induced lesions. 相似文献
5.
The and metabolism of 1,2- 3H-progesterone was studied in estrogen-stimulated and control vaginae of ovariectomized mice. Employing two-dimensional thin-layer chromatography, gas-liquid chromatography and metabolite “trapping” techniques, the major and minor pathways for progesterone metabolism were determined and shown to involve saturation of the Δ4-double bond to yield 5α-pregnane compounds and reduction of the C20 and C3 ketone groups to form 20α- and 3α- and 3β-hydroxy derivatives, respectively. The quantities of 20β-hydroxy metabolites and 5β-epimers that were detected were considered not to be significant. The major metabolites formed by untreated tissues following incubation in the presence of both high (10?6M) and low (10?8M) progesterone concentrations were 3α-hydroxy-5α-pregnan-20-one and 5α-pregnane-3,20-dione. Although these two derivatives were also found in sizable quantities in estrogen-treated tissues, a marked increase (5-fold) in the rate of C20 ketone reduction at high progesterone concentrations (10?6M) to yield 20α-hydroxy-4-pregnen-3-one was demonstrated. Following intravaginal administration of 3H-progesterone , only progesterone and 3α-hydroxy-5α-pregnan-20-one were retained in appreciable quantities through 2 hr, suggesting rapid loss of 20α-hydroxy-4-pregnen-3-one and the 5α-pregnanediols from this tissue under conditions. 相似文献
6.
M J Duchesne A A Attallah J B Lee 《Biochemical and biophysical research communications》1975,64(1):196-203
PGA1 was incubated with rabbit renal cortical homogenates containing HSA (0–4.5%). The ability of this tissue to readily metabolize PGA1 progressively decreased with increasing HSA levels in the incubates The rate of disappearance of 3H-PGA1 was twice as rapid in rats treated with salicylic acid (S. A.) in comparison to control animals; since only 30% of the injected radioactivity was bound to the plasma of the S.A. treated rats, as compared to 90% bound to control plasma, an association may exist between the degree of binding of 3H-PGA1 and its rate of clearance. The studies indicate that PGA1 interaction with HSA decreases its metabolism , and slows down its clearance , implicating HSA as a possible factor in prostaglandins metabolism . 相似文献
7.
In vivo biosynthesis of -linolenic acid in plants 总被引:6,自引:0,他引:6
C G Kannangara B S Jacobson P K Stumpf 《Biochemical and biophysical research communications》1973,52(2):648-655
[1-14C]acetate was readily incorporated into unsaturated fatty acids by leaf slices of spinach, barley and whole cells of and . In these systems the [14C] label in newly synthesized oleate and linoleate was approximately equally distributed in the C1–9 and the C10–18 fragments obtained by reductive ozonolysis of these acids, whereas in a-linolenic acid over 90% of the total [14C] was localized in the C1–9 fragment. While [1-14C]oleic acid was converted by whole cells of to [1-14C]linoleic and [1-14C]linolenic acids, [U-14C]oleic acid yielded [U-14C]linoleic acid but a-linolenic acid was labeled only in the carboxyl terminal carbon atoms. When spinach leaf slices were supplied with carboxyl labeled octanoic, decanoic, dodecanoic, tetradecanoic and octadecanoic acids, only the first three acids were converted to a-linolenic acids while the last two acids were ineffective. Thus we suggest that (a) linoleic acid is not the precursor of a-linolenic acid and (b) 12:3(3, 6, 9) is the earliest permissible trienoic acid which is then elongated to a-linolenic acid. 相似文献
8.
The benzo[b]thiophene and l-methylindole analogs of tryptophan have been tested for their ability to act as substrates for aromatic-L-amino acid decarboxylase . Neither of the analogs showed detectable decarboxylation under conditions that produced significant rates of decarboxylation of tryptophan. In addition, both analogs inhibited the decarboxylation of tryptophan and phenylalanine by the system. 相似文献
9.
The metabolism of prostacyclin (PGI2) was investigated in Cynomolgus monkey. Following intravenous infusion of 11-[3H]-PGI2 for three days, pooled urine was extracted with Amberlite XAD-2, then chromatographed and purified by Sephadex LH-20, and reverse phase column chromatography. Radioactive fractions were converted to appropriate derivatives for identification by gas chromatography mass spectrometry. Twelve metabolites were characterized, the major of which was 6-keto-PGF1α, accounting for 13% of the urinary radioactivity. The metabolic pathways are similar to those observed earlier in the rat. The excretion of substantial amounts of unchanged 6-keto-PGF1α indicated that the monkey was not able to metabolize PGI2 as avidly as the rat. 相似文献
10.
Elizabeth M.K. Leovey Niels H. Andersen Pamela Bissonette 《Prostaglandins & other lipid mediators》1979,17(1):19-37
, originally introduced as an inadvertent contaminant in solutions used for evaluating the stability of prostaglandins, proved to lead to the rapid disappearance of the cyclopentenone unit of PGA2 (as monitored by circular dichroic spectroscopy). The cyclopentenone unit is converted, in various metabolites, to a 9-keto, 9α or 9β-hydroxy group lacking the ring unsaturation. The major EtoAc-soluble 9-hydroxy metabolite (Compound-I) was shown to be 9α, 15α-dihydroxy-2,3,4,5-tetranor-13--prostenoic acid. Similar tetranor 9-hydroxy metabolites with one additional degree of unsaturation, and with a 9β-hydroxy group, also occur but these have not been fully characterized. Only two of the wide range of 9-keto metabolites are fully characterized by mass spectral (MS) data: 9,15-oxo-2,3,4,5-tetranorprostanoic acid and 9,15-oxo-2,3,4,5-tetranor-13--prostenoic acid. The water soluble metabolites have not been characterized further.The fully characterized metabolites together with MS data from mixtures of minor metabolites indicate that can perform the following transformations: β-oxidation, dehydrogenation at C-15, reduction of the enone carbon-carbon double bonds (both Δ10,11 and Δ13,14), reduction of the 9-ketone, and possibly migration of the cyclopentyl double bond (Δ10,11 → Δ11,12). metabolizes 15-epimeric PGA2 equally readily with the production of similar products. PGA1 affords less 9-keto metabolites with compound I constituting 33% of the product by HPLC analysis. displays some enantioselectivity, PGA2 and 15-epi-PGA2 are each metabolized more rapidly than their enantiomers. Other prostaglandins appear to be less readily metabolized. 相似文献
11.
The metabolic fate of the side-chain of propranolol has been studied in the rat and with liver preparations using drug labelled with 14C in the isopropyl group. Oxidative N-dealkylation to yield acetone was the major route of metabolism . Direct deamination to form isopropylamine was a very minor pathway of metabolism of propranolol by rat liver. In the intact rat only 1.4% of an intra-peritoneal dose of propranolol was excreted as isopropylamine in urine. In addition, isopropylamine administered to a rat was rapidly excreted unchanged in urine. Thus, if a similar metabolic pattern obtains in man, it seems unlikely that part of the pharmacological effects of propranolol can be attributed to this active metabolite. 相似文献
12.
Metabolism of prostaglandin A. I. The kidney cortex as a major site of PGA2 degradation 总被引:2,自引:0,他引:2
The antihypertensive and natriuretic prostaglandin A2 (medullin) has been isolated and identified in rabbit renal papilla. Since PGA2, unlike prostaglandin F2 (PGE2) and prostaglandin F2α (PGF2α), is not metabolized by the lung, studies were undertaken to determine if the site of PGA2 metabolism is in the renal cortex where its primary vasodilatory and natriuretic effects occur. In experiments, homogenates of renal cortex and outer medulla were incubated with 3H-PGA2 (0.2 μc, 20 μg) at 37°C for 30 minutes. A metabolite(s) less polar than 3H-PGA2 was observed following silicic acid chromatography of acidic lipid extracts of cortical, but not outer medullary homogenates. In studies, 3H-PGA2 (2 μc, 50 μg) was injected into the renal artery of the rabbit and blood withdrawn from the ipsilateral renal vein. At least three less polar major metabolites of PGA2 were observed in the plasma within 15 seconds following injection. No appreciable 3H-PGA2 was observed in venous plasma 30 seconds following injection of 3H-PGA2. In contrast to plasma, the major urinary metabolites were more polar than PGA2. The present study reveals that PGA2 is almost completely metabolized in a single passage through the rabbit kidney suggesting this organ is a major site of PGA2 metabolism. 相似文献
13.
Relationships between perinatal mortality, disrupted uteroplacental function and prostaglandin metabolism have been studied in Zn-deficient rats. Uterine contractility , placental blood flow , and uterine and placental prostaglandin synthesis from [1?14C] arachidonic acid were investigated at day 22 of pregnancy. High amplitude uterine contractions were almost completely eliminated and utero-placental blood flow was decreased by 85% by Zn deficiency. Synthesis of [1?14C]-prostaglandin E2, F2α and 6-keto-F1α from [1?14C] arachidonic acid decreased significantly in uterine tissue but increased in placentae. These possibly inter-related effects may contribute to the high perinatal mortality observed in Zn deficiency. 相似文献
14.
F Shapiro D Brickley-Parsons M J Glimcher 《Archives of biochemistry and biophysics》1979,198(1):205-211
The biosynthesis in vivo of the two reducible aldimine crosslinks of immature rabbit articular collagen, hydroxylysinohydroxynorleucine and hydroxylysinonorleucine, is demonstrated. The peak amount of crosslink was detected 1–2 weeks following labeling of the cartilage with [14C]lysine. The subsequent diminution which occurred was due primarily to a decrease in the amount of hydroxylysinohydroxynorleucine. Natural reduction of the aldimine crosslinks in vivo did not occur. Glucosylgalactosyl hydroxylysine and galactosylhydroxylysine, in a ratio, were synthesized. Seventy-three percent of the hydroxylysine residues were glycosylated. [3H]NaBH4 reduction of non-14C-labeled cartilage showed diminished amounts of reducible crosslink with time and the presence of hexosyl lysines and hexosyl hydroxylysines in mature articular cartilage. 相似文献
15.
《Insect Biochemistry》1987,17(3):433-437
We have studied the metabolism of the hyperglycemic/cardioacceleratory peptide periplanetin CC-2 (pGlu-Leu-Thr-Phe-Thr-Pro-Asn-Trp-NH2), in Periplaneta americana using both in vitro and in vivo methods. We focused on metabolism in hemolymph, and homogenates of fat body (a presumed target organ) and Malpighian tubules (previously suggested to degrade the nonpurified cardioacceleratory factors). Despite using low concentrations (6 nM) of [4-3H-Phe]CC-2, enzymatic degradation in homogenates of fat body and Malpighian tubules proceeded with of ∼ 1 hr, while degradation in hemolymph was much slower. We injected low doses (1–2 pmol) of [3H]CC-2 into adult female cockroaches and analyzed hemolymph samples at various times; we determined the in vivo to be about 1 hr. We conclude that rate of secretion may be more important in controlling physiological levels of this peptide than rate of degradation. 相似文献
16.
The hypoglycemic agent, 2-tetradecylglycidic acid (TDGA), administered in vivo lowered the concentration of plasma glucose and ketone bodies but raised the concentration of liver and plasma triglycerides in 10-day-old suckling rats. Phospholipid and cholesterol content of the plasma and liver were unaffected by drug treatment. TDGA inhibited the in vivo oxidation of [1-14C]palmitate but not that of [1-14C]decanoate. In suckling rat liver perfusion, TDGA totally inhibited ketone body formation from palmitate and depressed ketone body production from decanoate by 20%. Liver ATP and ADP content in the presence of TDGA decreased although this was probably a reflection of the increased triglyceride content of the liver since the was the same as control livers. The results are discussed in relation to the diet and to the inhibition of carnitine acyl transferase in suckling rats. 相似文献
17.
Four assay methods were tested for the measurement of Δ1-piperideine-2-carboxylate, a proposed alicyclic ketimino acid intermediate in the pathway of lysine metabolism to l-pipecolate, and the product of d-amino acid oxidase on d-pipecolate. The method using Δ1-piperideine-2-carboxylate reductase from Pseudomonas putida was found to be most sensitive and specific. Measurement of Δ1-piperideine-2-carboxylate by reduction with NaBH4 and ninhydrin assay of the resultant pipecolate, by direct acidic ninhydrin assay, and by o-aminobenz-aldehyde assay were less desirable because of lower sensitivity and specificity. Two synthetic methods for preparing l-[14C]pipecolate from the racemic dl-[14C]pipecolate were investigated. Incubation of dl-[14C]pipecolate with a combination of d-amino acid oxidase and Δ1-piperideine-2-carboxylate reductase or d-amino acid oxidase and NaBH4 totally inverted the d-isomer to the l-isomer, with as an intermediate in each cycle of interconversion. No purification except desalting through a Dowex 50 (H+) column was necessary in order to recover l-[14C]pipecolate in pure form. The yield was 95–97% compared to <50% in the conventional method. 相似文献
18.
oxidation of diethylstilbestrol (DES) by peroxidase preparations from horse radish or mouse uterus in the presence of hydrogen peroxide yields β-dienestrol, which is also a major metabolite of DES in several mammalian species. The oxidation reaction appears to involve reactive intermediates, presumably the semiquinone and quinone of DES, since nonextractable binding to salmon sperm deoxyribonucleic acid and bovine serum albumin was found. The peroxidase-catalyzed oxidation of DES to reactive metabolites in estrogen target organs may be related to the organ toxicity of this synthetic estrogen. 相似文献
19.
Carlos E. Argaraña Carlos A. Arce Hector S. Barra Ranwel Caputto 《Archives of biochemistry and biophysics》1977,180(2):264-268
In vitro incorporation of [14C]tyrosine into the C-terminal position of the α subunit of tubulin was not affected by 4 mm cycloheximide. This inhibitor of protein synthesis was used for in vivo experiments. The in vivo incorporation of [14C]tyrosine into soluble brain protein of cycloheximide-treated rats was 10% of that of untreated rats. Treatment with vinblastine sulfate of the soluble brain protein showed that the incorporation of [14C]tyrosine into tubulin was higher in cycloheximide-treated than in untreated rats with respect to the incorporation into the total soluble protein. In the case of cycloheximide-treated rats, about 60% of the radioactivity incorporated into protein was released by the action of carboxypeptidase A, whereas 10% was liberated from the protein of untreated rats. The radioactive compound released by the action of carboxypeptidase A was identified as [14C]tyrosine. The α and β subunits of tubulin from animals that received [14C]tyrosine were separated by polyacrylamide gel electrophoresis. The radiosactivity ratio of subunits of tubulin from cycloheximide-treated rats was threefold higher than that of untreated rats. When a mixture of [14C]amino acids was injected, the radioactivity ratio of subunits of tubulin was similar for cycloheximide-treated and untreated rats. The results reported are consistent with the assumption that the α subunit of tubulin can be tyrosinated in vivo. 相似文献
20.
Göran Hansson 《Prostaglandins & other lipid mediators》1979,18(5):745-771
The metabolism of the prostaglandin F2α analogues, 15-methyl-Δ4--PGF1α and 16,16-dimethyl-Δ4--PGF1α, has been investigated in the cynomolgus monkey and the human female. The two analogues, tritium labelled in the 9β-position, were administered by intramuscular injections into the monkeys and by subcutaneous injections into the human. Excretion of tritium labelled products were followed in urine (in both species) and feces (in monkeys only) and several metabolites were identified by GC/MS. The analogues were found to be resistant to the 15-hydroxy dehydrogenase and furthermore the degradation by β-oxidation was delayed. About 13% of the given dose of 15-methyl-Δ4--PGF1α was excreted unchanged into urine and feces from the monkey. The corresponding figure for 16,16-dimethyl-Δ4--PGF1α was about 20%. In addition, a large part of the metabolites had the carbon skeleton intact and were only metabolized by ω-oxidation. The relative resistance to degradation of these two analogues is likely to be the basis for their prolonged pharmacological activity. 相似文献