Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Side-chain cleavage (SCC) of endogenous cholesterol in adrenal mitochondria isolated from ACTH-treated rats indicates that the size of the reactive cholesterol pool depends on the reducing precursor. At optimal concentrations of reductant, this pool was typically at least 2 times greater for isocitrate than for succinate. Succinate-supported reactions were rapidly completed, were highly sensitive to a 2-min preincubation, and failed to deplete spectrally detected P-450SCC-cholesterol complexes. Cholesterol SCC with 1 mM isocitrate exhibited 2-3 times more fast-phase metabolism, a pronounced slow phase, insensitivity to preincubation, and 60% depletion of spectrally detected cholesterol-P-450SCC complexes. Addition of bovine serum albumin (BSA) and EDTA, either during homogenization or directly to the incubation, prevented preincubation losses in response to succinate and removed most of the difference between succinate and isocitrate activities. This effect of BSA/EDTA was reversed within 5 min by octanoate by a mechanism that was enhanced by Ca2+. These distinct reductant characteristics suggest that only a subpopulation of mitochondria or of pools of activity within individual mitochondria can support cholesterol SCC with succinate while isocitrate is necessary for the remainder. The rapid responses of succinate-supported metabolism to preincubation or to octanoate suggest depletion of a critical factor for cholesterol metabolism. Metabolism of added 20 alpha-hydroxycholesterol or deoxycorticosterone established that NADPH remained fully available after succinate-supported cholesterol metabolism had stopped or after preincubation. Cessation of pregnenolone formation, therefore, results from a failure to supply cholesterol, not inadequate NADPH. The preincubation effect suggests loss of an energy-dependent component that enhances this supply of cholesterol. One possibility tested was that GTP, an activator of intermembrane cholesterol transfer (Xu et al. (1989) J. Biol. Chem. 264, 17674-17680), was being lost. Added GTP slightly activated succinate-supported pregnenolone production but did not prevent preincubation-induced losses. alpha-Ketoglutarate, which can generate matrix GTP, is an effective reductant that, in combination with succinate, prevents preincubation-induced losses.
Mol Cell Endocrinol 1990 Oct 22
PMID:Heterogeneous pools of cholesterol side-chain cleavage activity in adrenal mitochondria from ACTH-treated rats: differential responses to different reducing precursors. 217 27

The recovery of both contractile performance and metabolic response of rat heart following 1 h of ischemia after equilibration with glucose + insulin (glucose-ischemia) or with pyruvate (pyruvate-ischemia), was tested in normoxic reperfusion in the presence of glucose + insulin, pyruvate, lactate or acetate. In glucose-ischemia only the reperfusion with pyruvate results in a complete recovery of the contractile force (left ventricular pressure, LVP) (170%) and good recovery of high energy phosphate compounds. Lower LVP and tissue energy charge were found in glucose reperfusion and even less in lactate and acetate reperfusion. Disappearance of the IMP accumulated during ischemia is evident only in the pyruvate reperfusion indicating a higher metabolic recovery. On the contrary in pyruvate-ischemia all types of reperfusion tested were effective in reactivating the contractile force (although acetate to a lesser extent); the contractile activity was accompanied by a good recovery of phosphocreatine, ATP, energy charge and by the decrease of IMP. Large decreases of adenine nucleotides and NADP and lower decreases of NAD are observed during ischemia/reperfusion in both systems. Pyruvate-ischemia is quite similar to, if not worse than glucose-ischemia, for all the metabolic parameters considered, but not worse for the possibility of recovery. Some specific effect of pyruvate should be exerted during the ischemic phase. The mechanism of pyruvate protection is discussed in relationship to: (i) the possible activation of pyruvate dehydrogenase, (ii) the activation of NADPH-dependent peroxide scavenging systems, (iii) the direct scavenging action of pyruvate on H2O2.
J Mol Cell Cardiol 1990 Feb
PMID:The protective action of pyruvate on recovery of ischemic rat heart: comparison with other oxidizable substrates. 218 87

Previous studies examining regulation of synthesis of Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase in rat liver have focussed on the induction of these enzymes by different diets and some hormones. However, the precise mechanism regulating increases in the activities of these enzymes is unknown and the factors involved remain unidentified. Considering that many of these metabolic conditions occur simultaneously with the increase of some NADPH consuming pathway, in particular fatty acid synthesis, we suggest that the activities of Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase could be regulated through a mechanism involving changes in the NADPH requirement. Here, we have studied the effect of changes in the flux through different NADPH consuming pathways on the NADPH/NADP ratio and on Glucose-6-Phosphate and 6-Phosphogluconate levels. The results show that: i) an increase in consumption of NADPH, caused by activation of fatty acid synthesis or the detoxification system which consumes NADPH, is paralleled by an increase in levels of these enzymes; ii) when increase in consumption of NADPH is prevented, Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase levels do not change.
Mol Cell Biochem 1990 Jun 25
PMID:Possible involvement of NADPH requirement in regulation of glucose-6-phosphate and 6-phosphogluconate dehydrogenase levels in rat liver. 219 19

Biliverdin reductase is the dual nucleotide-dependent cytosolic enzyme that converts biliverdin to the bile pigment, bilirubin, and displays extensive microheterogeneity in rat organs. The enzyme is unique in having two pH optima. The present study reports on the tissue-dependent pattern of developmental expression of the reductase in rat liver and brain. When analyzed by Western immunoblotting, two closely migrating immunoreactive proteins were detected in the liver cytosol during the first 2-3 weeks after birth; the protein with greater mobility was not detected in the liver of adult aged animals (6 months old) and was present at low levels in rats during the first week of life. The faster migrating protein was not detected in the brain cytosol at any stage of development. Furthermore, in the brain the total amount of enzyme protein increased as the animal matured, whereas in the liver the enzyme protein level decreased with age. When the purified enzyme was analyzed, age-related changes in the variant composition of the enzyme in the liver were noted. Although in both adult and newborn animals (14 days old) the purified enzyme, when subjected to isoelectric focusing, separates into five net charge forms (pl 6.23, 5.91, 5.76, 5.61, and 5.48), the relative abundance of the variants notably differed in the two preparations. In addition, when the purified preparations were subjected to two-dimensional electrophoresis, although both purified preparations separate into three molecular weight forms (Mr 30,400, 30,700, and 31,400) one species (Mr 31,400, pl = 5.77), which was very prominently expressed in the newborn, was essentially absent in the adult. Biliverdin reductase activity of the liver cytosol with both NADPH (pH 8.7) and NADH (pH 6.7) exhibited developmental changes, with the activity increasing after birth, reaching a peak on day 14, and decreasing to low levels in the adult. The existence of a close correlation between development of biliverdin reductase activity in the brain and liver and that of heme oxygenase in these organs is noted. The suggestion is made that the reductase is not a passive component of the heme degradation pathway; rather, its activity could become limiting in the elimination of heme degradation products.
Mol Pharmacol 1990 Oct
PMID:Multiple forms of biliverdin reductase: age-related change in pattern of expression in rat liver and brain. 223 89

The levels of hepatic mRNAs for several enzymes involved in drug metabolism were measured following administration to rats of either phenobarbitone or 2-allyl-2-isopropylacetamide. There was a substantial elevation in the mRNA levels for cytochromes P450 IIB1, IIB2, and IIIA1, epoxide hydrolase, glutathione-S-transferase Ya/Yc subunit, UDP-glucuronosyltransferase isoenzyme (UDPGTr-2), NADPH-cytochrome P450 oxidoreductase, and 5-aminolevulinate synthase. When rats were treated with hemin, together with inducing drug, there was a marked reduction in the induced levels of these mRNAs, with decreases in the range of 55-95%. Basal levels of these mRNAs in the noninduced rat liver were also lowered by hemin administration. Nuclear run-on transcriptional experiments showed that hemin administration substantially lowered both the basal and drug-induced transcriptional activities of the genes for cytochrome P450IIB1/IIB2 and 5-aminolevulinate synthase. In contrast, the mRNA for heme oxygenase was elevated by hemin treatment, whereas the mRNA levels of beta-actin, albumin, and ornithine transcarbamylase, used as controls, were not affected. Treatment of rats with clofibrate resulted in increased levels of mRNA for cytochrome IVA1 and, in addition, those for cytochromes P450IIB1 and P450IIB2. Hemin administration repressed the induction of mRNA levels for cytochromes P450IIB1 and IIB2 but not that for cytochrome P450 IVA1. Additionally, the induction of P450IAI by beta-naphthoflavone was not affected by hemin. The results suggest that heme may negatively control the induction of cytochromes P450IIB1 and IIB2 and other hepatic enzymes by phenobarbitone and phenobarbitone-like drugs and perhaps play a role in regulating drug metabolism. There is, however, no evidence at present as to whether heme has a direct role in such a mechanism or whether injected hemin promotes a secondary response.
Mol Pharmacol 1990 Oct
PMID:Hemin administration to rats reduces levels of hepatic mRNAs for phenobarbitone-inducible enzymes. 223 90

Purified bovine P-450scc, the cholesterol side-chain cleaving P-450 in adrenal cortex mitochondria, was found to catalyze a deoxycorticosterone 6 beta-hydroxylase reaction. A turnover number (moles of product formed/min/mol of P-450) of 12 was found similar to that for cholesterol side chain cleavage activity. Conversion was dose-dependent in terms of P-450scc and no reaction took place when any one of the required electron donating components such as NADPH, NADPH-adrenodoxin reductase, or adrenodoxin was omitted. These results confirm and extend earlier observations that 21-hydroxypregnenolone is transformed into both deoxycorticosterone and 6 beta-hydroxydeoxycorticosterone by incubation of adrenal gland slices.
J Steroid Biochem Mol Biol 1990 Sep
PMID:Adrenal P-450scc catalyzes deoxycorticosterone 6 beta-hydroxylase reaction. 224 47

Hepatic ischemia induced in vivo by ligation of the left hepatic lobe of rats for up to 2 hr had no effect on cytochrome P-450, cytochrome c reductase, or lobe histology; however, cytochrome b5 increased with ischemia duration. Ethylmorphine demethylation decreased 35% after 2 hr of ischemia. Reperfusion of tissue previously made ischemic for up to 2 hr was associated with appreciable necrosis as well as decreases in cytochrome P-450, cytochrome b5, cytochrome c reductase, and ethylmorphine demethylation. Serum alanine transaminase and aspartate transaminase concentrations were increased by reperfusion of previously ischemic tissue. Reperfusion of the previously ischemic lobe for 18 hr was associated with a greater loss of cytochromes P-450 and b5, cytochrome c reductase, and ethylmorphine demethylation than reperfusion for 1 hr. The total decrease in cytochrome P-450 and b5 content was equal to the decrease in total microsomal heme content, although cytochrome P-450 decreased more than cytochrome b5. Ethoxyresorufin deethylation by hepatic microsomes from 3-methylcholanthrene-treated rats was decreased by ischemia-reperfusion; however, pentoxyresorufin dealkylation by hepatic microsomes from phenobarbital-treated rats was not, suggesting specific cytochrome P-450 isozyme loss. In vitro NADPH-dependent lipid peroxidation in hepatic microsomes from control and phenobarbital- and 3-methylcholanthrene-treated rats resulted in a selective decrease of ethoxyresorufin but not pentoxyresorufin dealkylation, similar to that observed in livers subjected to ischemia-reperfusion in vivo. These data suggest that cytochrome P-450, ethylmorphine demethylation, and ethoxyresorufin deethylation are more susceptible to ischemia-reperfusion injury than cytochrome b5 or pentoxyresorufin dealkylation.
Mol Pharmacol 1990 Dec
PMID:Effects of hepatic ischemia-reperfusion injury on the hepatic mixed function oxidase system in rats. 225 Jun 63

The NADPH:5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) [EC 1.1.1.50] which catalyzes the reversible conversion of 5 alpha-pregnane-3,20-dione (5 alpha-dihydroprogesterone; 5 alpha-DHP) to 3 alpha-hydroxy-5 alpha-pregnan- 20-one (3 alpha-,5 alpha-tetrahydroprogesterone; 3 alpha,5 alpha-THP) was purified to apparent homogeneity from female rat anterior pituitary cytosol by a three step micro-purification procedure. Specific activity of purified 3 alpha-HSOR was enriched 438-fold from that in pituitary cytosol using successive ion exchange, chromatofocusing and affinity column chromatography purification steps. 3 alpha-HSOR appears to be a monomer with an approximate molecular weight of 36 kDa and an isoelectric point of about 5.75. The purified enzyme appears as a single protein staining band (36 kDa) when examined by polyacrylamide gel electrophoresis and with both silver or Coomassie blue staining. Under non-dissociating electrophoretic conditions, all of the 3 alpha-HSOR activity co-migrated with the 36 kDa protein staining band. The purified enzyme in the presence of the preferred cofactor, NADPH, has an apparent Km for 5 alpha-DHP of 82 nM and a Vmax of 1.2 mumol of 3 alpha,5 alpha-THP formed per mg protein/30 min. The Km for NADPH was 0.71 microM. In the oxidative direction, the enzyme in the presence of NADP+ has a Km for 3 alpha,5 alpha-THP of 1.4 microM and a Vmax of 9.7 mumol of 5 alpha-DHP formed per mg protein/30 min. The Km for NADP+ was 1.6 microM.
J Steroid Biochem Mol Biol 1990 Oct
PMID:Purification of the NADPH:5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase from female rat pituitary cytosol. 226 52

Crude extracts from a number of helminths including Schistosoma intercalatum and Fasciola hepatica were able to detoxify known aldehydic products of lipid peroxidation. A major route for alk-2-enal and alka-2,4-dienal detoxification in parasitic helminths was via glutathione conjugation and glutathione transferase appeared to be responsible for the activity. As yet uncharacterised NADPH-linked systems may provide an important secondary pathway for detoxification of alk-2-enals and alka-2,4-dienals in parasitic helminths. The free-living nematode Panagrellus redivivus had higher active NADH/NADPH-linked aldehyde reduction systems compared to parasitic helminths. The NADH linked and NADPH linked reductions in P. redivivus were mitochondrial and cytosolic activities respectively. NADH/NADPH-linked systems may be responsible for alkanal reduction in helminths as there is no evidence of conjugation of alkanals with glutathione. P. redivivus and Haemonchus contortus were also able to oxidise aldehydes via NAD/NADP-linked systems.
Mol Biochem Parasitol
PMID:Strategies for detoxification of aldehydic products of lipid peroxidation in helminths. 227 Jan 3

From the cytosol fraction (supernatant fluid at 105,000 g) of chicken liver, 3 alpha-hydroxysteroid dehydrogenase was purified to an apparently homogeneous state by differential precipitation with ammonium sulfate, followed by column chromatographies with DE 51, DEAE-Toyopearl, and Sephadex G-100. Finally the dehydrogenase was purified 103-fold on the basis of the cytosol fraction. Polyacrylamide gel electrophoretic analysis in the presence of sodium dodecyl sulfate (SDS) revealed that molecular weight of the purified enzyme was 66 kDa, while that of the native dehydrogenase in the absence of SDS was estimated as 660 kDa or more from the peak of the enzyme in elution profile from Sephacryl S-200 column chromatography. The dehydrogenase required NADPH specifically for reduction of 3-oxo group of 5 beta-androstanedione (Km = 1.6 microM). Optimal temperature for 3-oxo reduction was 50 C in incubation for 10 min.
J Steroid Biochem Mol Biol 1990 Nov 30
PMID:Purification and characterization of 3 alpha-hydroxysteroid dehydrogenase from chicken hepatic cytosol. 227 41


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