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:1.1.1.3 (HSD)
3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dehydrogenase activity of the aspartokinase I-homoserine dehydrogenase I complex isolated from Escherichia coli K12 is subject to a cooperative activation by K+ or Rb+, which is characterized by a Hill coefficient of approximately 2. Ionic strength has little effect on the Hill coefficient for this activation process; however, high ionic strength appears to increase the enzyme's affinity for K+ and decrease its affinity for Rb+. The Vmax of the K+-activated dehydrogenase is greater than that of the Rb+-activated dehydrogenase. The results of a study of the competition between K+ and Rb+ in the activation process suggest the presence of an activated species containing both K+ and Rb+. The cooperative activation by K+ is antagonized by Na+ via a process that is noncooperative with respect to Na+. The MgATP-2- complex, a substrate for the kinase activity of aspartokinase I-homoserine dehydrogenase I, has a marked effect on the K+ activation of the dehydrogenase activity. Kinetic studies of this effect of MgATP-2- on the K+ requirement of the dehydrogenase at pH 8.9 indicate that: (a) activation by a monovalent cation is essential in the presence as well as in the absence of MgATP-2-; (b) the concentration of K+ required to activate fully the dehydrogenase is reduced in the presence of MgATP-2-; (c) activation of the dehydrogenase by K+ is noncooperative in the presence of MgATP-2-; and (d) the maximum velocity for the dehydrogenase catalyzed oxidation of homoserine is greater in the presence of MgATP-2- than in its absence. Based on these results, a simple model consistent with these data is proposed. Destruction of the kinase activity and the threonine sensitivity of the aspartokinase-homoserine dehydrogenase complex by treatment with 5,5'-dithiobis(2-nitrobenzoic acid) or by incubation at pH 9 also converts the K+ activation of the dehydrogenase from a cooperative to a noncooperative process. Marked protection of the enzyme against loss of threonine sensitivity at pH 9 is afforded by MgATP-2- plus K+ and homoserine. The apparent molecular radius of the enzyme complex as determined by gel filtration at pH 8.85 in the presence of threonine or MgATP-2- plus K+ and homoserine is dependent on the enzyme concentration. The observed apparent molecular radii of 70 A at high enzyme concentrations and 61 A at low enzyme concentrations are consistent with the enzyme's undergoing a concentration-dependent dissociation from a tetrameric to a dimeri
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PMID:Aspartokinase I-homoserine dehydrogenase I of Escherichia coli K12 (lambda). Activation by monovalent cations and an analysis of the effect of the adenosine triphosphate-magnesium ion complex on this activation process. 16 50

In an attempt to study the renal effects of Calcitonin (porcine CT) in the rabbit, the excreted fractions of filtered water, osmolality, sodium, potassium and chloride, and the calcium and phosphorus urinary excretions were studied during isotonic (ISD) and hypertonic (HSD) saline diuresis. Four doses (0.1, 0.8, 4 and 20 IU MRC/kg were perfused during one hour in I.S.D.; 4 and 20 IU MRC/kg in HSD. During ISD, Calcitonin at doses of 4 and 20 IU MRC/kg/hr significantly increased the diuresis and the Na+, Cl-, K+, PO4 3-, Ca2+ excreted fractions. This effect was also observed, to a lesser extent, at a dose of 0.8 IU MRC/kg/hr, whereas 0.1 IU MRC/kg/hr produced no significant effect. During ISD, a log dose related effect of CT appeared to exist with all studied parameters. Moreover, a biphasic pattern of free-water clearance was observed during ISD: this parameter increased during the first half hour of CT perfusion, and then decreased dramatically. During HSD, CT perfusion induced a decrease of free-water reabsorption and urinary osmolality/plasma osmolality ratio. These results suggest that the diuretic effect and saliuretic effect of CT (in the rabbit) are mainly the consequence of the decrease of the proximal reabsorption of sodium. The possibility of a second site of action is discussed. The diuretic effects of CT are compared to data observed with the well-known diuretic drugs.
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PMID:Calcitonin diuretic effect in the rabbit. 68 Jun 32

LH is required to maintain the activity of 3 beta-hydroxysteriod dehydrogenase/delta 5----4-isomerase (3 beta HSD) in testicular Leydig cells. The objective of the present study was to determine whether LH and effectors such as forskolin, which act via the intracellular cAMP signal transduction pathway, can regulate the expression of 3 beta HSD in rat Leydig cells in vitro. Primary cultures of Leydig cells were prepared from testes of adult rats and treated with oLH, forskolin, (Bu)2cAMP, or cholera toxin. The effects of treatment on 3 beta HSD activity were measured using [3 alpha-3H]dehydroepiandrosterone as substrate. Immunoreactive 3 beta HSD was quantified by denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting with a polyclonal antiserum against 3 beta HSD. The synthesis of 3 beta HSD was quantified after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitated cellular lysates of Leydig cells radiolabeled with L-[35S]methionine. The levels of 3 beta HSD mRNA were quantified by Northern analysis and hybridization with a cDNA encoding testicular 3 beta HSD (rat type I). A cell-free protein-synthesizing system was used to test the ability of 3 beta HSD mRNA to be translated into immunoreactive 3 beta HSD. 3 beta HSD activity increased 3.5- and 5.0-fold in Leydig cell cultures treated with forskolin (1 microM) and (Bu)2cAMP (1 mM), respectively, compared with control cultures. Maximal activity was attained after 48-72 h and maintained through 120 h of treatment. The increase in 3 beta HSD activity could be accounted for quantitatively by increases in the steady state levels and the rates of synthesis of 3 beta HSD. The cellular levels of immunoreactive 3 beta HSD increased 4.0- and 7.6-fold in Leydig cells treated with forskolin and (Bu)2cAMP, respectively. Moreover, both of these effectors increased by 6- to 8-fold the levels of newly synthesized 3 beta HSD after 24-72 h of treatment. Ovine LH, forskolin, cholera toxin, and (Bu)2cAMP increased the cellular levels of 3 beta HSD mRNA in a dose-dependent manner. The magnitude of the increases ranged from 2- to 42-fold, compared with that in control cultures, after 12 h of treatment. Maximal responses were effected by 1 ng/ml ovine LH, 1 microM forskolin, 1 ng/ml cholera toxin, and 1 mM (Bu)2cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Expression of testicular 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase: regulation by luteinizing hormone and forskolin in Leydig cells of adult rats. 131 36

3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) was purified greater than 500-fold from human liver cytosol. The purification was monitored using 5 beta-[3H]dihydrocortisol (5 beta-DHF) as substrate. Electrophoretically homogeneous enzyme was obtained using a procedure that involved ammonium sulfate precipitation and three successive column chromatography steps: DEAE-cellulose, hydroxylapatite and Blue-Sepharose. The enzyme is a monomer since the native molecular weight was found to be 37,000, using a calibrated Sephadex G-75 column, and the denatured subunit molecular weight was determined to be 38,500, by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The enzyme had a pI of 5.6-5.9. The 3-ketosteroids: cortisol, testosterone, progesterone and androstenedione, were not substrates for 3 alpha-HSD indicating that a saturated 4,5 double bond was required for substrate activity. The conformation at the 5 position, however, did not influence substrate activity since 5 alpha- and 5 beta-DHF and 5 alpha-dihydrotestosterone were all reduced at similar rates. The purified enzyme preferred NADPH to NADH as a cofactor and showed a broad peak of activity in the pH range of 6.8-7.4. The apparent Km for 5 beta-DHF was 18 microM. The enzyme was markedly stabilized by 50 mM phosphate buffer containing 10 to 20% glycerol at 4 degrees C. Freezing and thawing of the enzyme resulted in a large loss of activity during early stages of the purification. This is the first report of the purification to homogeneity of 3 alpha-HSD from human tissue.
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PMID:Purification and properties of human hepatic 3 alpha-hydroxysteroid dehydrogenase. 139 Feb 84

In addition to demonstrating evidences of increased sympathetic nervous system activity and marked left ventricular hypertrophy in salt-sensitive hypertensives, our group has also reported increased weight gain with salt overload in these patients. The increased weight gain suggests volume expansion, a situation already shown to increase plasma levels of a Na, K-ATPase inhibitor. Therefore, in the present study, digoxin-like factor (DLF) serum levels, spontaneous salt ingestion, nifedipine hypotensive effect, and plasma renin activity were evaluated in essential hypertensive subjects. Thirteen essential hypertensive outpatients were studied sequentially on an ad lib diet, a low salt diet (LSD = 30 mEq Na/day), and a high salt diet (HSD = LSD + 171 mmol/L NaCl/day), 1 week each. On the seventh day of LSD and HSD, DLF levels, mean blood pressure (MBP) response to nifedipine (10 mg sublingual), and plasma renin activity were measured. The MBP percent change from the seventh day of LSD to the seventh day of HSD (salt sensitivity) ranged from -13.7 to 20.9%. A positive correlation (r = 0.64, P < .01) was observed between salt sensitivity and 24-h urinary sodium excretion with an ad lib diet. The DLF serum levels correlated with the salt sensitivity both on LSD (r = 0.50, P < .05) and on HSD (r = 0.53, P < .05). Salt sensitivity was positively correlated with the difference of response to nifedipine between HSD and LSD (r = 0.78, P < .001). Plasma renin activity correlated inversely with DLF on LSD (r = -0.51, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Higher salt consumption, digoxin-like factor, and nifedipine response are associated with salt sensitivity in essential hypertension. 141 33

5 alpha-Dihydrotestosterone 3 alpha(beta)-hydroxysteroid dehydrogenase [3 alpha(beta)-HSDH] [EC 1.1.1.50/EC 1.1.1.51] which catalyses the conversion of 5 alpha-dihydrotestosterone (5 alpha-DHT) to both 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol was purified to an apparent homogeneous state using cytosol of three human hyperplastic prostates by a 4-step purification procedure. After each purification step 3 alpha-HSDH activity was coincident with 3 beta-HSDH activity. On average, specific 3 alpha-HSDH activity was enriched 856-fold, specific 3 beta-HSDH activity 749-fold compared to human prostatic cytosol using anion exchange, hydrophobic interaction, gel filtration and affinity chromatography. Examination of the purified enzyme by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS) revealed a single protein band with silver staining. The molecular weight of the enzyme was estimated as 33 kDa by SDS-polyacrylamide gel electrophoresis and as 28 kDa by Sephacryl S-200 gel filtration indicating that the native 3 alpha(beta)-HSDH is a monomer. In the presence of the preferred co-factor, NADPH, the purified enzyme had a mean apparent Km for 5 alpha-DHT of 3.9 microM and a Vmax of 93.3 nmol (mg protein)-1 h-1 with regard to 3 alpha-HSDH activity, and a Km of 6.3 microM and a Vmax of 20.6 nmol (mg protein)-1 h-1 with regard to 3 beta-HSDH activity.
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PMID:Purification and properties of the 5 alpha-dihydrotestosterone 3 alpha(beta)-hydroxysteroid dehydrogenase from human prostatic cytosol. 160 44

This study was performed to determine whether resuscitation with a single bolus of 7.5% NaCl/6% Dextran 70 (hypertonic saline/Dextran, HSD) could restore renal function following hemorrhage. Chronically instrumented, conscious pigs were hemorrhaged 28 ml/kg. This level of hemorrhage reduced mean arterial pressure (MAP) and cardiac output (CO) to nearly half, renal blood flow (RBF) to approximately 25%, and glomerular filtration rate (GFR) and urine flow (V) to less than 10% of their initial values. A single, 4 ml/kg bolus injection of HSD increased MAP and RBF to approximately 80% of baseline values and restored CO and GFR to levels which were significantly different from control values. These improvements were sustained for 2 h with no further treatment. Urine flow transiently increased although not to pre-hemorrhage values, and then subsided. Plasma osmolality increased from 275 to 282 mOsm/kg H2O, and plasma sodium increased from 141 to 149 mEq/l. Recovery following administration of an equal volume of normal saline was significantly less for all variables. Euvolemic animals showed no response in MAP, CO, RBF, or GFR when treated with HSD although V, osmotic and sodium excretion increased. These results demonstrate that resuscitation with HSD following hemorrhage not only restores MAP and CO, but maintains renal function as well.
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PMID:Hypertonic saline/dextran improves renal function after hemorrhage in conscious swine. 170 8

In rabbits, laser Doppler flow probes were placed in the jejunum and on the renal cortex. Pulsed Doppler probes were implanted on the abdominal aorta and superior mesenteric and femoral arteries for measuring blood flow velocity. Cardiac output was measured by thermal dilution. Either 30% or 40% of the calculated blood volume was withdrawn through a carotid catheter. After 30 or 60 minutes, an initial bolus of either lactated Ringer's (LR, 16 ml/kg) or 7.5% hypertonic saline/6% dextran 70 (HSD; 4 ml/kg) IV was followed by unlimited IV LR (administered as rapidly as possible) to restore systemic arterial blood pressure to the prehemorrhage levels. With HSD, arterial pressure corrected more rapidly (p less than 0.05), and the initial hemodilution was greater (p less than 0.05), but there were no differences by two hours. With HSD, cardiac output (90%-100% vs. 130%-160% of control; p less than 0.05), plasma Na+ (139-140 mM vs. 146-148 mM; p less than 0.05) and plasma osmolarity (292-295 mOsm vs. 308-310 mOsm; p less than 0.05) were all significantly higher than the values with LR, but there was no effect on blood flow velocities through the infrarenal aorta, femoral artery, or superior mesenteric artery. Renal cortical perfusion (56% vs. 97% of control; p less than 0.05) and jejunal mucosal perfusion (83% vs. 162% of control; p less than 0.05) were significantly higher with HSD. HSD had no detectable effect on bacterial translocation at 24 hours. Thus: 1) HSD restores blood flow more rapidly to the gut mucosal and kidney microcirculations than initial resuscitation with LR; 2) the mechanism could be associated with a transient hemodilution and persistent increases in plasma Na and osmolarity, which reduce hemorrhage-induced cell swelling and blood viscosity changes; and 3) laser Doppler analysis could aid in the diagnosis of reperfusion injury after shock.
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PMID:Microcirculatory flow changes after initial resuscitation of hemorrhagic shock with 7.5% hypertonic saline/6% dextran 70. 170 22

A 3 alpha-reducing activity of 5 alpha-dihydrotestosterone (5 alpha-DHT) was found in pig adrenal cytosol. The enzyme (3 alpha-hydroxysteroid dehydrogenase: 3 alpha-HSD) has been purified to homogeneity from pig adrenal cytosol by ammonium sulfate precipitation followed by DEAE-cellulose, 2', 5'-adenosine diphosphate-Sepharose and Sephadex G-100 column chromatographies. The molecular weight was estimated to be 33,000 and 39,000 by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Isoelectric point was estimated to be 8.5 by isoelectric focusing. The Km and Vmax values for 5 alpha-DHT in the reduction were 10.2 microM and 10.6 nmol/min/mg. The enzyme utilized reduced nicotinamide adenine dinucleotide phosphate (NADPH) or reduced nicotine amide adenine dinucleotide (NADH) in the reduction as a cofactor, but it preferentially required NADPH rather than NADH. Furthermore, the purified enzyme catalyzed not only 3 alpha-reduction of 5 alpha-DHT (9.65 nmol/min/mg), but also catalyzed 20 alpha-reduction of 17 alpha-hydroxyprogesterone (0.58 nmol/min/mg). The enzyme activity of 3 alpha-HSD was strongly inhibited by Hg2+, but it was not inhibited by medroxyprogesterone acetate and some anti-inflammatory agents. No remarkable differences was demonstrated between 3 alpha-HSD and 20 alpha-HSD activity under the influence of heat treatment, divalent cation, anti-inflammatory agents and some inhibitory steroids. These results strongly suggest that 3 alpha-HSD purified from pig adrenal cytosol is a bi-functional enzyme catalyzing 3 alpha- and 20 alpha-HSD activities.
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PMID:[Purification and some properties of 3 alpha-hydroxysteroid dehydrogenase from pig adrenal cytosol]. 180 59

The Type I (mineralocorticoid) receptor has identical affinities in vitro for cortisol and aldosterone. It has been suggested that the selective role of aldosterone in regulating sodium homeostasis relies on the microsomal enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD). This enzyme converts cortisol to its inactive metabolite, cortisone, preventing cortisol from binding to the Type I receptor. We have isolated human cDNA clones encoding 11-HSD from a human testis cDNA library by hybridization with a previously isolated rat 11-HSD cDNA clone. The cDNA contains an open reading frame of 876 bases, which predicts a protein of 292 amino acids. The sequence is 77% identical at the amino acid level to rat 11-HSD cDNA. The mRNA is widely expressed, but the level of expression is highest in the liver. Hybridization of the human 11-HSD cDNA to a human-hamster hybrid cell panel localized the single corresponding HSD11 gene to chromosome 1. This gene was isolated from a chromosome 1 specific library using the cDNA as a probe. HSD11 consists of 6 exons and is at least 9 kilobases long. The data developed in this study should be applicable to the study of patients with hypertension due to apparent mineralocorticoid excess, a deficiency in 11-HSD activity.
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PMID:The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. 188 95


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