Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: Y22D7AL .14
 53,079 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combined administration of CRH and vasopressin to man now offers a powerful means to directly assess the pituitary corticotroph reserve. A double blind, randomized, placebo-controlled, cross-over trial offered the opportunity to perform the combined CRH/lysine vasopressin (LVP) test (100 micrograms ovine CRH, followed by 1 IU LVP over 15 min) on 3 different occasions without treatment in 10 normal male subjects. We showed that peak ACTH plasma levels after stimulation had wide intersubject variation, whereas they were remarkably stable in a given individual, with a mean intraclass correlation coefficient of 0.90 (95% confidence limits, 0.74-0.96). Peak ACTH plasma levels after CRH/LVP administration were not significantly correlated with basal plasma cortisol levels (r = -0.14; P > 0.45), but were strongly and inversely correlated with peak cortisol plasma levels after Cortrosyn stimulation (0.25 mg, im; r = -0.78; P < 0.0001). These data provide the first evidence that the overall hypothalamic-pituitary-adrenocortical axis has an intrinsic activity that is constitutively fixed for a given individual. The power of the combined CRH/LVP test offers a unique means to measure a genuine corticotroph phenotype in each individual.
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PMID:The combined corticotropin-releasing hormone/lysine vasopressin test discloses a corticotroph phenotype. 804 53

We report a preliminary evaluation of an immunoinhibition assay for creatine kinase isoform quantification. The procedure employs the monoclonal antibody CKM-G01, which inhibits the native M subunit of creatine kinase. The antibody does not inhibit the M subunit modified by removal of lysine by plasma carboxypeptidase N. Residual activity after treatment with the antibody is therefore due to serum delysinated isoforms. The ratio inhibited/residual activity correlated directly with the ratio tissue/serum isoforms. Analysis of the total imprecision of isoform ratio measurement gave a coefficient of variation between 5.9 and 21.1%. Reference intervals for the ratio were 0.14-0.79 in females and 0.19-0.95 in men (p = 0.0046). Analytical and clinical comparison with alternative isoform procedures gave good results, showing that this assay can be used as alternative to the widely accepted electrophoretic method for measurement of the creatine kinase isoform ratio.
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PMID:An immunoinhibition assay for determination of creatine kinase isoforms in serum. 808 23

Thirty-nine Thoroughbred and Quarter Horse yearlings were used in two 112-d experiments to determine the effect of lysine and threonine supplementation on growth and development. Yearlings were individually fed three dietary treatments that consisted of a pelleted concentrate containing corn, oats, and soybean meal fed to appetite twice daily and Coastal bermuda grass hay group-fed at a rate of 1 kg/100 kg BW. Three concentrates were tested: (A) basal, (B) basal plus .2% lysine, and (C) basal plus .2% lysine, and .1% threonine. Feed intake, weight, withers height, girth, hip height, body length, and hoof growth (Exp. 1) were recorded every 28 d, and initial and final radiographs taken for estimating bone mineral content. Final croup fat thickness was measured ultrasonically in Exp. 1, and initial and final croup fat measured in Exp. 2. Blood samples were taken every 28 d for determination of serum urea N and protein in Exp. 2. Average daily feed intake (as-fed) was 8.8 +/- .14, 9.0 +/- .13, and 9.2 +/- .13 kg (P < .09), ADG was .57 +/- .02, .64 +/- .02, and .67 +/- .02 kg/d (P < .02), and girth gain was 9.7 +/- .49, 10.1 +/- .46, and 11.3 +/- .47 cm (P < .05) for Treatments A, B, and C, respectively. Gain:feed ratios in Exp. 1 were 70.5, 70.8, and 75.5 g/kg (P > .10) and in Exp. 2 were 61.7, 70.8, and 70.2 g/kg (P < .10) for Treatments A, B, and C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of supplemental lysine and threonine on growth and development of yearling horses. 815 22

Tyrosyl-tRNA synthetase from Bacillus stearothermophilus is a dimeric enzyme which displays half-of-sites reactivity with respect to the binding of both tyrosine and ATP. The binding of both substrates follows Michaelis-Menten kinetics. Mutation of lysine 233 to alanine (K233A) decreases the affinity of the active subunit for ATP at both saturating and subsaturating tyrosine concentrations (from the Hill plot, kcat = 0.56 s-1, nH = 1.54, Kd = 372 mM at 50 microM tyrosine). In addition, this mutant displays sigmoidal kinetics (characteristic of positive cooperativity) with respect to the binding of ATP. These two effects can be reversed by the addition of NaCl (0.5 m final concentration) or by a second alanine mutation at either position K230 or T234. The effect of either NaCl or second site mutation is to increase the binding affinity of the K233A mutant for ATP (KATP values are 22 mM for the K233A mutant in the presence of 0.5 M NaCl, 0.16 mM for the K230A/K233A mutant, and 0.14 mM for the K233A/T234A mutant). With the restoration of the tight binding of ATP, Michaelis-Menten kinetics are restored since the kinetic analysis of tyrosyl adenylate formation involves only binding of ATP to the active subunit. It is likely that the physical mechanism for the positive cooperativity present in the K233A mutant actually exists in the wild-type enzyme but is not observed kinetically due to the initial binding of ATP to the active subunit. These results indicate that, in some cases, a decrease in substrate affinity is sufficient to introduce cooperativity into a noncooperative enzyme.
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PMID:Mutation of lysine 233 to alanine introduces positive cooperativity into tyrosyl-tRNA synthetase. 825 98

One hundred eighty-one maternal-line (Yorkshire x Landrace x Chester White or purebred Landrace) sows were used to determine effects of dietary protein concentration during lactation on voluntary feed intake of sows and sow and litter performance. Throughout gestation, sows received 1.8 kg/d of a 14% CP corn-soybean meal diet. Sows were assigned to dietary treatments based on parity (range = 1 to 9) and expected farrowing date. Treatments were corn-soybean meal diets that contained 13.6 (Low, L), 15.5 (Medium, M), 17.5 (High, H), or 19.2 (Very High, VH) % CP. Calculated lysine content of diets was .62 (L), .76 (M), .90 (H), and 1.05 (VH) %. Sows had ad libitum access to their assigned diets from the day of parturition until weaning (24.6 +/- .46 d postpartum). Pigs were cross-fostered irrespective of dietary treatment until d 3 postpartum. Diet had a cubic effect (P < .05) on the lactational weight change of sows (L, -9.1; M, -2.1; H, -4.6; VH, .8 kg; SE = 1.57) but had no effect on change in backfat depth during lactation or on voluntary feed intake of lactating sows (x = 6.0 kg/d). Litter size at weaning (9.6 +/- .17 pigs) was similar across dietary treatments; however, diet linearly affected (P < .05) daily litter weight gain (L, 2.01; M, 2.12; H, 2.18; VH, 2.14 kg; SE = .05). Postweaning interval to estrus averaged 5.2 +/- .25 d and was unaffected by dietary treatments. Our data suggest that dietary protein concentrations between 13.6 and 19.2% do not influence voluntary feed intake of lactating sows or weaning-to-estrus interval.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response of maternal-line sows to dietary protein concentration during lactation. 837 39

Three 35-d trials involving 288 crossbred weanling pigs (initial weight, 7.1 kg; age, 28 d) were used to determine the separate and interactive effects of two floor space allowances (.28 and .14 m2/pig) and three dietary lysine levels (NRC recommended, NRC+ .1% crystalline lysine-HCl, and NRC+ .2% crystalline lysine-HCl) on growth performance and several factors that measure variation within pens. Each trial was conducted as a 2 x 3 factorial arrangement of treatments in a randomized complete block design. There were four pens (four pigs per pen) for each of the six treatment combinations in each trial. The lysine x floor space allowance interaction was not significant (P = .25) for daily gain, daily feed intake, or gain/feed. Restriction of the floor space allowance decreased (P < .001) daily gain and daily feed intake, but gain/feed was not affected. The humoral immune response, as measured by the level of antibodies produced after two injections of ovalbumin, was not affected by floor space allowance. Addition of .1 and .2% crystalline lysine-HCl improved daily gain (P < .07), gain/feed (P < .10), and humoral immune response (P < .05) and was without effect (P = .28) on feed intake. Natural logarithms of variance, coefficients of variation, and range of daily gain and body weights were not changed by floor space allowance or dietary lysine level. Pigs on adequate and restricted floor space allowances responded similarly to dietary lysine levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of dietary lysine levels on performance and immune response of weanling pigs housed at two floor space allowances. 846 39

The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS). The KL4 peptide was synthesized to resemble the amino acid pattern of surfactant protein B (SP-B). Forty-seven infants with RDS were treated within 4 h of birth with the KL4-peptide/phospholipid mixture, called KL4-Surfactant. The average arterial-to-alveolar oxygen tension ratios (a/A O2) of 39 patients included in efficacy analyses rose from pretreatment values of 0.14 +/- 0.02 (mean +/- SEM) to 0.40 +/- 0.04 (normal value > or = 0.40) by 12 h of age. Mean airway pressures and oxygenation index values fell concomitantly, and expansion of the lungs was observed on radiographs. The median duration of mechanical ventilation was 5.0 d. Of the 39 included infants, 29 required only a single dose. Radiographic data indicate that those patients requiring a second instillation of KL4-Surfactant but not showing a sustained rise in a/A O2 ratios did, in fact, exhibit expansion of alveoli in the lung. There were no RDS-related deaths; the incidence of complications was no higher than found in other comparable published studies. The data demonstrate that the synthetic peptide, KL4, which mimics the hydrophobic and hydrophilic pattern of SP-B, when formulated in an aqueous dispersion with the phospholipids DPPC and POPG, creates a strong and durable surfactant activity as judged by expansion of pulmonary alveoli and improvement of gas exchange in infants with RDS.
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PMID:The efficacy and safety of KL4-surfactant in preterm infants with respiratory distress syndrome. 854 50

The metal binding sites of isolated F1 ATPase from spinach chloroplasts (CF1) and from the thermophilic bacterium Bacillus PS3 (TF1) have been studied by EPR and pulsed EPR spectroscopy using Mn(II) as a paramagnetic probe. After dialysis in the presence of EDTA, purified CF1 retains 0.14 +/- 0.07 Mg(II) and approximately 0.75 +/- 0.25 ADP. TF1 retains 0.31 +/- 0.03 Mg(II) and 0.08 +/- 0.01 nucleotide (ADP + ATP) after the same treatment. Supplementing known quantities of Mn(II) to metal-depleted CF1 allowed a spectroscopic characterization of the bound Mn(II) cations, for which the EPR spectra at X- and Q-band are reported. The zero field splitting parameters of Mn(II) are derived from the simulation of the EPR signal recorded at Q-band for a sample supplemented with 0.3 Mn/CF1. The values, magnitude of D approximately 200 x 10(-4) cm-1 and magnitude of E approximately 40 x 10(-4) cm-1 suggest that the Mn(II) binds to CF1 in a slightly distorted environment. The ESEEM spectra of complexes of Mn(II) with CF1 were also recorded for different Mn/CF1 ratios. For a complex with 0.8 Mn/CF1, the ESEEM spectrum shows two frequencies at 3.7 and 8.6 MHz that are attributed to the magnetic coupling with 31P with a hyperfine coupling constant of magnitude of A approximately 5.3 MHz, reflecting the interaction with a phosphate group from the endogenous ADP molecule. This demonstrates close proximity of the strong affinity metal site M1 and the endogenous ADP binding site N1, and binding of the ADP beta-phosphate to the divalent metal cation. For Mn(II) complexes with higher Mn/CF1 ratios, new frequency components below approximately 5 MHz are resolved in the spectra in addition to the peaks from 31P. From a comparison of the CF1 spectra and their magnetic field dependence across the Mn(II) EPR line shape with those of Mn(II) complexes with imidazole, glycine, poly-L-lysine, and nucleotide ligands, it is concluded that additional metal binding sites are filled at higher Mn contents and that these involve 14N donors. It is suggested that the most probable set of ligands of the divalent metal(s) for these additional metal sites in CF1 includes a lysine residue, in line with a previous proposal [Houseman, A. L. P., Morgan, L., LoBrutto, R., & Frasch, W. D. (1994) Biochemistry 33, 4910-4917]. Similar experiments for a Mn(II) complex with TF1 (0.4 Mn/TF1) showed no interaction with 31P; instead modulations are detected in the ESEEM below approximately 5 MHz that are attributed to a 14N ligand. This is tentatively attributed to the deprotonated amine of Lys-162 from a beta subunit, on the basis of the structural data available for the mitochondrial F1 complex. Addition of the substrate ATP to this Mn.TF1 complex leads to the formation of a ternary Mn.TF1.ATP complex with coordination of the Mn(II) by a phosphate group from the ATP as judged from the ESEEM results (magnitude of A(31P) approximately 4.5 MHz). An increase in the hyperfine coupling constant of 31P of the phosphate bound to Mn(II) to magnitude of A(31P) approximately 5.1 MHz is observed after incubation of the ternary complex at room temperature. This is interpreted as a significant rearrangement of the coordination sphere of the Mn(II) in the M1 site of the Mn.TF1.ATP complex and may reflect conformational changes of catalytic significance that occur in the nucleotide binding site during unisite hydrolysis of ATP to ADP by this complex.
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PMID:Metal binding sites of H(+)-ATPase from chloroplast and Bacillus PS3 studied by EPR and pulsed EPR spectroscopy of bound manganese(II). 870 62

1. We have investigated whether changes in extracellular ion composition and substrate deprivation modulate basal and/or bradykinin-stimulated L-arginine transport and release of nitric oxide (NO) and prostacyclin (PGI2) in porcine aortic endothelial cells cultured and superfused on microcarriers. 2. Saturable L-arginine transport (Km = 0.14 +/- 0.03 mM; Vmax = 2.08 +/- 0.54 nmol min-1 (5 x 10(6) cells)-1) was pH insensitive and unaffected following removal of extracellular Na+ or Ca2+. 3. Cationic arginine analogues, including L-lysine and L-ornithine, inhibited L-arginine transport, whilst 2-methylaminoisobutyric acid, beta-2-amino-bicyclo[2,2.1]-heptane-2-carboxylic acid, L-phenylalanine, 6-diazo-5-oxo-norleucine, L-glutamine, L-cysteine and L-glutamate were poor inhibitors. 4. Deprivation of L-arginine (30 min to 24 h) reduced intracellular free L-arginine levels from 0.87 +/- 0.07 to 0.40 +/- 0.05 mM (P < 0.05) and resulted in a 40% stimulation of L-arginine, L-lysine and L-ornithine transport. 5. L-arginine and NG-monomethyl-L-arginine (L-NMMA), but not N omega-nitro-L-arginine methyl ester (L-NAME), trans-stimulated efflux of L-[3H]arginine. 6. Depolarization of endothelial cells with 70 mM K+ reduced L-arginine influx and prevented the stimulation of transport by 100 nM bradykinin, but agonist-induced release of NO and PGI2 was still detectable. 7. Basal rates of L-arginine transport and NO release were unaffected during superfusion of cells with a nominally Ca(2+)-free solution. Bradykinin-stimulated L-arginine transport was insensitive to removal of Ca2+, whereas agonist-induced NO release was abolished. 8. Although bradykinin-stimulated NO release does not appear to be coupled directly to the transient increase in L-arginine transport, elevated rates of L-arginine influx via system y+ in response to agonist-induced membrane hyperpolarization or substrate deprivation provide a mechanism for enhanced L-arginine supply to sustain NO generation.
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PMID:Regulation of L-arginine transport and nitric oxide release in superfused porcine aortic endothelial cells. 874 90

The effect of mimosine on a perfused area of skin tissue was studied using an isolated perfusion technique. Four mature Angora wethers (body weight 35 (SE 2.3) kg) were cannulated bilaterally with indwelling silicone catheters in the superficial branches of the deep circumflex iliac artery and vein. Mimosine (40 mg/kg metabolic weight (W)0.75) per d) was infused intra-arterially into one iliac artery of each goat for 3 d and saline was infused in the contralateral (control) iliac artery. Iliac venous blood samples were taken from both sides along with arterial samples from the carotid artery. Mimosine infusion elevated plasma mimosine in the carotid artery (52.6 (SEM 19.21) mumol/l) and iliac vein on the saline-treated side to 54.1 (SEM 16.31) mumol/l and in the iliac vein on the mimosine-treated side to 191.3 (SEM 19.14) mumol/l (P < 0.01). Mimosine decreased feed intake (2.3 v. 0.6 kg/d, SEM 0.29; P < 0.001) and water consumption (5.2 v. 1.3 litres/d, SEM 0.67; P < 0.001). Mimosine did not cause defleecing in the area of infusion and was cleared from the bloodstream within 12 h of cessation of infusion. The following effects were also observed during mimosine infusion: decrease in plasma amino acids to half pre-infusion values (methionine 22.7 v. 13.1 mumol/l, SEM 1.41; lysine 95.9 v. 37.4 mumol/l, SEM 4.28; P < 0.001); decreases in plasma triiodothyronine (1495 v. 695 ng/l, SEM 43.1; P < 0.001), thyroxine (61.5 v. 19.5 micrograms/l, SEM 1.8; P < 0.001) and insulin (28.7 v. 17.3 microIU/ml, SEM 1.89; P < 0.01) concentrations; increase in plasma cortisol (14 v. 62 micrograms/l, SEM 0.35; P < 0.001) concentration; decreases in levels of plasma Zn and Mg (0.97 v. 0.49 mg/l, SEM 0.063; P < 0.001 and 21.4 v. 14.6 mg/l, SEM 1.74; P < 0.001 respectively). All reported variables returned to their normal values 24 h after cessation of mimosine infusion except feed intake which was affected for a longer period. Mohair length and diameter were not affected by mimosine infusion. The toxicity of mimosine may be due to the drastic depletion of Zn and Mg in the blood as mimosine possesses very strong chelating properties and is excreted in the urine as a chelate.
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PMID:Effects of mimosine administered to a perfused area of skin in Angora goats. 878 92


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