Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Water deprivation for 48 hr with its accompanying decrease in food intake significantly lowered the in vitro rate of hexobarbital metabolism by hepatic microsomes isolated from male rats. Pair-fed rats allowed water ad libitum had a significantly lower level of hexobarbital metabolism than those deprived of water. Rats starved for 24 hr with or without water also had levels of hexobarbital metabolism significantly lower than their controls; with those animals allowed water ad libitum, the level was significantly lower than for those deprived of water. In vivo hexobarbital "sleeping time" experiments were in general agreement with these results. The in vitro metabolism of aniline was increased in both male and female rats following 24 hr starvation and in female rats (but not males) the effect was greater when water was allowed than when deprived. The differences between hydrated and dehydrated animals were not attributable to reduction in concentration of microsomal protein or the water content of liver. It is concluded that water consumption accentuates the effect of food deprivation on hepatic microsomal metabolism.
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PMID:Effect of water and food deprivation on hepatic microsomal metabolism of hexobarbital and aniline. 99 38

The delta 9 desaturase activity and the 14-C radioactivity of the de novo synthesized fatty acids incorporated into microsomal lipids and serum triglycerides were measured under different nutritional conditions. The results obtained indicate a correlation between the values of the three parameters studied after starvation or after refeeding Purina chow or either a high carbohydrate or a high protein diet. These data suggest that liver lipogenesis and delta 9 desaturase activities respond to the same regulatory factors.
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PMID:Adaptive changes in delta 9 desaturase activity in rat liver. 113 25

In this work the microsomal lauric acid omega-hydroxylation, fatty acid peroxisomal beta-oxidation, and the levels of cytochrome P-450 IVA1 were studied in liver tissue from starved rats. Starvation increased the peroxisomal beta-oxidation and the microsomal hydroxylation of fatty acids. The correlation between these activities would support the proposal that both processes are linked, contributing in part to catabolism of fatty acids in liver of starved rats.
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PMID:Modulation of rat liver peroxisomal and microsomal fatty acid oxidation by starvation. 139 71

The isoform of cytochrome P450 that catalyzes the 12 alpha-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one, an intermediate in the conversion of cholesterol to cholic acid, was purified to homogeneity from rabbit liver microsomes. The extent of purification in the various steps was judged by an assay involving high performance liquid chromatography. The purified enzyme showed a single band on SDS-polyacrylamide gel electrophoresis (M(r) = 50,000). The NH2-terminal amino acid sequence is as follows: Val-Leu-Trp-Gly-Leu-Leu-Gly-Ala-Leu-Leu-Met-Val-Met-Val-Gly-, which is different from that of any other P450s so far reported. The specific content of the enzyme was 13.3 nmol of cytochrome P450/mg of protein. Upon reconstitution with NADPH-cytochrome P450 reductase and cytochrome b5, the P450 enzyme showed a high activity of 12 alpha-hydroxylation with a turnover number of 36.6 min-1 at 37 degrees C. The omission of either cytochrome P450 or NADPH-cytochrome P450 reductase resulted in complete loss of activity, and the omission of cytochrome b5 resulted in 40% loss of activity. Antibodies prepared from mouse inhibited the 12 alpha-hydroxylase activity of rabbit liver microsomes about 90% and that of the rat liver microsomes 50%. The enzyme activity was not inhibited by other antibodies raised against other forms of P450 that catalyze different monooxygenation reactions toward xenobiotics or endogenous substrates. Anti-cytochrome b5 antibody inhibited the activity 40%, suggesting the functional role of this protein, and anti-reductase inhibited the activity almost completely. The microsomal enzyme activity was markedly elevated by starvation or streptozotocin administration to the animals. However, an immunoblotting experiment showed no correlation between the enzyme activity and the amount of protein, suggesting that post-translational modification may occur.
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PMID:Purification and characterization of 7 alpha-hydroxy-4-cholesten-3-one 12 alpha-hydroxylase. 140 Apr 44

Microsomes from the liver of sea bass (Dicentrarchus labrax) were shown to hydroxylate lauric acid at subterminal positions. The cytochrome P-450 system converted lauric acid to several mono-hydroxylated metabolites including omega-1 hydroxylaurate, which was the major metabolite (44% of total products). In addition, omega-2, omega-3, omega-4 and a small amount (2.3%) of omega hydroxylaurates were found. Reaction products were identified using thin-layer chromatography (TLC) and gas chromatography/mass spectrometry (GC/MS). Oxidation reactions were dependent upon O2 and NADPH, and did not occur with boiled microsomes or in the presence of a mixture of CO/O2. Hydroxylation proceeded linearly up to 20 min at 28 degrees C for protein concentrations below 380 micrograms. Treatment of fish with benzo(a)pyrene (BP) (20 mg/kg) drastically increased xenobiotic metabolism (ECOD, EROD and BPMO activities), but no difference in laurate hydroxylase activity was observed between untreated and treated fish. Starvation strongly enhanced laurate hydroxylase activity, and resumption of feeding reduced by half this increase of activity. In all of the experiments we did not observe any modification of the regioselectivity of lauric acid hydroxylation by this microsomal in-chain hydroxylating system. We suggest that cytochrome P-450 enzymes involved in lauric acid and xenobiotics metabolism are regulated independently.
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PMID:Subterminal hydroxylation of lauric acid by microsomes from a marine fish. 152 63

The profile of the changes in the peroxisomal fatty acid oxidation activity in rat liver was compared with that in microsomal omega-oxidation under various conditions such as a 2-week administration of phenoxyacetic acid derivatives and perfluorinated compounds, short and long-term administration of clofibrate and bezafibrate, high-fat diet feeding, starvation and diabetes. The results were summarized as follows: 1) when phenoxyacetic acid derivatives and perfluorinated compounds were administered, there was a significant correlation in the increase of the activities between peroxisomal fatty acid oxidation and microsomal omega-oxidation. 2) On the long-term administration (79 weeks) of peroxisome proliferators the activities of the enzymes were significantly reduced, but the levels were still higher than the control level in a similar manner. 3) On high-fat diet feeding the patterns of the changes in the activities of peroxisomal fatty acid oxidation, carnitine acetyltransferase and microsomal omega-oxidation were similar to each other, differing from the changes in the activities of microsomal aminopyrin demethylase and mitochondrial carnitine palmitoyltransferase. 4) Under starved and diabetic conditions, co-induction of peroxisomal fatty acid oxidation and microsomal omega-oxidation was observed. From these results it is suggested that 1) the biosynthesis of these enzymes would be regulated on the gene expression of the nearby domain and 2) peroxisomal fatty acid oxidation and microsomal omega-oxidation were co-operatively regulated in order to achieve fatty acid metabolism smoothly.
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PMID:Characteristics of peroxisome proliferation: co-induction of peroxisomal fatty acid oxidation-related enzymes with microsomal laurate hydroxylase. 191 1

Diallyl sulfide (DAS) and other organosulfur compounds inhibit chemically induced carcinogenic and toxic responses in rodent model systems. A possible mechanism of action is the inhibition of the hepatic cytochrome P450IIE1-dependent bioactivation of the procarcinogens and protoxicants. Previous work showed competitive inhibition by DAS of N-nitrosodimethylamine (NDMA) demethylase activity in vitro, and a reduction in the microsomal level of P450IIE1 after in vivo treatment with DAS. The present studies demonstrated a time- and dose-dependent decrease of hepatic microsomal P450IIE1 activity, induction of P450IIB1 and pentoxyresorufin dealkylase activity, and moderate induction of ethoxyresorufin dealkylase activity by oral DAS treatment. DAS treatment elevated P450IIB1 mRNA but had no effect on P450IIE1 mRNA. Treatment with putative metabolites of DAS, diallyl sulfoxide and diallyl sulfone, led to similar modulations in monooxygenase activities, but the decrease of P450IIE1 activity by the sulfone occurred more rapidly. In studies in vitro, diallyl sulfone caused a metabolism-dependent inactivation of P450IIE1, but such inactivation was not observed with DAS or diallyl sulfoxide. The profile of microsomal testosterone metabolism after DAS treatment indicated an enhancement of P450IIB1-dependent 16 beta-hydroxylase activity, and a decrease in 6 beta-hydroxytestosterone production possibly related to a lower level of P450IIIA1 or IIIA2. When rats were subjected to a 48-hr fast and DAS treatment, the starvation-induced microsomal P450IIE1 level was decreased by DAS. Inhibition of hepatotoxicity due to exposure to P450IIE1 substrates, CCl4 and NDMA, by DAS was observed under a variety of treatment schedules.
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PMID:Modulation of rat hepatic microsomal monooxygenase enzymes and cytotoxicity by diallyl sulfide. 201 58

Incubation of rat liver microsomes with 1-propanol and 1-butanol in the presence of NADPH and of the spin trapping agent 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) allowed the detection of free radical intermediates tentatively identified as 1-hydroxypropyl and 1-hydroxybutyl radical, respectively. Microsomes isolated from rats treated chronically with ethanol (EtOH) or with the combination of starvation and acetone treatment (SA), exhibited a two-fold increase in the ESR signal intensity as compared to untreated controls, whereas no increase was observed in phenobarbital-induced (PB) microsomes. Consistently, in reconstituted membrane vesicles, ethanol-inducible cytochrome P450IIE1 was twice as active as phenobarbital-inducible P450IIB1 in producing 1-butanol free radicals. In the microsomal preparations from EtOH and SA pretreated rats the addition of antibodies against cytochrome P450IIE1, but not of preimmune IgGs, lowered the ESR signal of 1-butanol radicals by more than 50%. The same antibodies decreased the free radical production by untreated microsomes by 35-40%, but were ineffective on microsomes from PB-treated animals. This indicated that cytochrome P450IIE1 is the major enzyme responsible for the free radical activation of alcohols in control and ethanol-fed rats. The generation of 1-hydroxybutyl radicals by EtOH microsomes was inhibited by 40, 48 and 68%, respectively, by the addition of isoniazid, tryptamine and octylamine, compounds known to specifically affect the NADPH oxidase activity of this isoenzyme. This effect was not due to the scavenging of the alcohol radical since none of these compounds affected the ESR signals originated from 1-butanol in a xanthine-xanthine oxidase system. When added to reconstituted membrane vesicles isoniazid, tryptamine and octylamine also decreased 1-butanol radical formation by P450IIE1 by 54, 38 and 66%, respectively. Such an inhibition corresponded to the effect exerted by the same compounds on O2- release from P450IIE1 containing vesicles. These results indicate that the capacity of cytochrome P450IIE1 to reduce oxygen is related to its ability to generate alcohol free radicals and suggest that ferric cytochrome P450-oxygen complex might act as oxidizing species toward alcohols.
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PMID:Role of ethanol-inducible cytochrome P450 (P450IIE1) in catalysing the free radical activation of aliphatic alcohols. 203 43

Low rates of triacylglycerol (TAG) biosynthesis were observed in cell-free extracts of Candida curvata, but rates were increased up to 10-fold by adding either alpha- or beta-cyclodextrins. Spheroplasts, whole or gently disrupted, had higher rates of incorporation of both [U-14C]glycerol 3-phosphate or [1-14C]oleate into triacylglycerol and the intermediates of its biosynthesis: lysophosphatic acid, phosphatidic acid and diacylglycerol. Fatty acyl-CoA synthetase was highest with palmitate, oleate and linoleate but was some 6- to 8-fold lower with stearate. Stearate and stearoyl-CoA were poorly incorporated into lipids. Subcellular fractionation of the spheroplasts into mitochondrial, microsomal, lipid bodies and supernatant fractions diminished the rates of 14C incorporation of oleate into triacylglycerol. By comparing the relative specific activities for each activity in each fraction, the fatty acyl-CoA synthetase activity appeared mainly in the lipid bodies, and that for phosphatidic acid formation was mainly in the mitochondrion; other activities were too weak and too dispersed for accurate assessment of their location. Recombining all the subcellular fractions restored triacylglycerol synthesizing activity. Omitting any single fraction from the mixture did not result in restoration of triacylglycerol synthesizing activity. Starvation of the yeast, which leads to utilization of the endogenous lipid reserves, stimulated fatty acyl-CoA synthetase activity, but diminished phosphatidic acid and triacylglycerol biosynthesis indicating probable induction of beta-oxidation in the peroxisomes and repression of lipid biosynthesis.
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PMID:Triacylglycerol synthesis in the oleaginous yeast Candida curvata D. 205 92

It is known that synthetic anti-estrogens such as tamoxifen bind to specific high affinity anti-estrogen binding sites (AEBS), which are distinct from estrogen receptors. These binding sites are widely distributed in animal and human tissues, the highest concentrations being found in the liver. The physiological role of these intracellular binding sites, which are located predominantly in the microsomal fraction, is currently unknown, as is the nature and identity of their endogenous ligands. In an attempt to gain information which may provide clues to the possible physiological role of these binding sites, studies were carried out to determine whether the concentration of these binding sites in rat liver was affected by a number of physiological variables. The results of these studies indicated that in the rat (i) liver AEBS increased progressively with age; (ii) liver AEBS concentration tended to be higher among females than males after 100 days of age; (iii) there was no significant variation in liver AEBS level with different phases of the estrous cycle; (iv) liver AEBS level was not significantly affected by castration in both males and females or by estradiol replacement in castrated females; (v) liver AEBS concentration increased significantly with increases in ambient temperature; (vi) there was no clearly detectable alteration in liver AEBS levels with changes in the light:dark cycle; (vii) starvation for 24, 48, and 72 hr increased liver AEBS by approximately 1.5-, 3-, and 2-fold, respectively, while refeeding decreased its level; and (viii) liver AEBS was not affected by increasing dietary fat content from 0.5% to 20% (w/w), but was increased modestly by the addition of cholesterol (2% w/w) to the diet. These observations identify several physiological variables which are associated with changes in liver AEBS concentration and suggest possible avenues for future studies to define the physiological role of these binding sites.
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PMID:Factors affecting anti-estrogen binding site concentration in rat liver. 206 21


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