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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The three-dimensional crystal structure of bovine trypsinogen at approximately pH 7.5 was initially solved at 2.6 A resolution using the multiple isomorphous replacement method. Preliminary refinement cycles of the atomic coordinates trypsinogen have been carried out first to a resolution of 2.1 A, and later to 1.9 A, using constrained difference Fourier refinement; During the process, structure factors Fc and phi c were calculated from the trypsinogen structure and final interpretation was based on an electron-density map computed with terms (2 Fo - Fc) and phases phic at a resolution of 1.9 A. Crystals of trypsinogen grown from ethanol-water mixtures are trigonal with space group P3121, and cell dimension a = 55.17 A and c = 109.25 A. The structure is compared with the bovine diisopropylphosphoryltrypsin structure at approximately pH 7.2, oirginally determined from orthohombic crystals by Stroud et al. (Stroud, R.M., Kay L.M., and Dickerson, R.E. (1971), Cold Spring Harbor Symp. Quant. Biol. 36, 125-140; Stroud, R.M., Kay, L.M., and Dickerson, R.E. (1974), J. Mol. Biol. 83, 185-208), and later refined at 1.5 A resolution by Chambers and Stroud (Chambers, J.L., and Stroud, R.M. (1976), Acta Crystallogr. (in press)). At lower pH, 4.0-5.5 diogen, with cell dimensions a = 55.05 A and c = 109.45 A. This finding was used in the solution of the six trypsinogen heavy-atom derivatives prior to isomorphous phase analysis, and as a further basis of comparison between trypsinogen and the low pH trypsin structure. There are small differences between the two diisopropylphosphoryltrypsin structures. Bovine trypsinogen has a large and accessible cavity at the site where the native enzyme binds specific side chains of a substrate. The conformation and stability of the binding site differ from that found in trypsin at approximately pH 7.5, and from that in the low pH form of diisopropylphosphoryltrypsin. The catalytic site containing Asp-102, His-57, and Ser-195 is similar to that found in trypsin and contains a similar hydrogen-bounded network. The carboxyl group of Asp-194, which is salt bridged to the amino terminal of Ile-16 in native trypsin or other serine proteases, is apparently hydrogen bonded to internal solvent molecules in a loosely organized part of the zymogen structure. The unusually charged N-terminal hexapeptide of trypsinogen, whose removal leads to activation of the zymogen, lies on the outside surface of the molecule. There are significant structural changes which accompany activation in neighboring regions, which include residues 142-152, 215-550, 188A-195. The NH group of Gly-193, normally involved in stabilization of reaction intermediates (Steitz, T.A., Henderson, R., and Blow, D.M. (1969), J. Mol. Biol. 46, 337-348; Henderson, R. (1970), J. Mol. Biol. 54, 341-354; robertus, J.D., Kraut, J., Alden, R.A., and Birkoft, J.J. (1972), Biochemistry 11, 4293-4303) in the enzyme, is moved 1.9 A away from its position in trypsin...
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PMID:Structure of bovine trypsinogen at 1.9 A resolution. 55 51

1. The cerebral depressant effect of 30 ml of aqueous ethanol diluted to 25% and administered orally to 16 volunteer subjects was compared with a control group of 15 volunteer subjects. 2. The two parallel forms of the Watson--Glaser Critical Thinking Appraisal tests were employed as a measure of cerebral function. 3. The control group showed a small but statistically insignificant improvement on retesting with Watson--Glaser test form ZM after preliminary administration of form YM. 4. The relationship between the blood alcohol time curve and the alcohol effect was analysed for each individual subject, each subject being used as his own control. 5. The main peak cerebral depressant effect was substantial and occurred on average 25.5 min before the attainment of the peak blood alcohol concentration. 6. There was no significant correlation between blood alcohol concentration and contemporaneous cerebral impairment (r = -0.01). 7. There was a highly significant correlation (r = 0.60) between the effect upon cerebral function and the gradient of the blood alcohol curve at that time.
Clin Sci Mol Med 1978 Jul
PMID:Blood alcohol and impairment of judgment. 66 68

1. The administration of a single oral dose of 2, 3, 4 or 5 g of ethanol/kg (43.5, 65.2, 87.0 or 108.7 mmol/kg respectively) to rats increases the rate of oxygen consumption by liver slices from animals killed 24--48 h later. 2. The increase in the rate of hepatic respiration can be blocked by incubation in a medium containing ouabain, an inhibitor of the sodium pump, or in a calcium-free medium. 3. The enhancement of oxygen uptake caused by a single dose of ethanol can be abolished by adrenalectomy or by prior administration of the alpha-adrenergic blocking agent phentolamine, and is markedly less in thyroidectomized animals. 4. It is suggested that the effect which is elicited by acute ethanol administration on respiration by liver slices is mediated by adrenaline and by throid hormones, both of which appear to exert a calorigenic effect by activation of the sodium pump. The results are discussed in relation to the changes in liver oxidative capacity induced by chronic alcohol ingestion.
Clin Sci Mol Med 1978 Oct
PMID:Effect of acute ethanol administration on liver oxidative capacity in rats. 71 49

Gluconeogenesis by isolated hepatocytes resulted in glucose release but insignificant rates of glycogen synthesis. The effectiveness of precursors was similar for hepatocytes from fed and starved chickens except for impaired gluconeogenesis from pyruvate when compared to lactate in lactate starved chicken hepatocytes. The impairment was caused by limitations in cytosolic NADH production as a result of the mitochondrial location of phosphoenolpyruvate carboxykinase in chicken liver. The order of effectiveness of precursors on hepatic gluconeogenesis was generally similar to the effects of precursors on increasing the plasma glucose concentration in vivo. The exceptions were caused by interactions with other precursors in vivo. The alteration of the NADH/NAD+ ratio by ethanol and ATP/ADP ratio by adenosine could play significant roles in the control of precursor conversion to glucose. Physiological glucagon concentrations stimulated gluconeogenesis from precursors entering the pathway both above and below the level of triose phosphates, and its effect were mimicked by dibutyryl cyclic AMP. Previous results on the effects of precursor and glucagon injection on the plasma glucose concentration of chickens in vivo can largely be explained by effects at the hepatic level. Isolated chicken and rat hepatocytes share many common features. Qualitatively the ordering of gluconeogenic effectiveness was similar but quantitive differences existed as a result of differing activities and cellular locations of enzymes. Neither preparation readily synthesised glycogen and the sensitivity to glucagon was similar.
Mol Cell Biochem 1978 Dec 22
PMID:Hepatic gluconeogenesis in chickens. 74 98

Circular dichroism spectra of DNA in ternary water-nonelectrolyte solutions (water--ethanol--isopropanol and water--ethanol--dioxane) show that the decrease in water content at various nonelectrolyte ratios leads to the transition of DNA from B- to A-form. Water activity values in B-A transition region were calculated. The transition takes place within the range of water activity and DNA conformations have been plotted on triangular diagrams.
Mol Biol (Mosk)
PMID:[B-A transition of DNA in aqueous solutions of nonelectrolytes]. 75 81

A mutant strain (2-20) isolated by growth on medium containing oligomycin and cycloheximide was also found to be cross resistant to antimyicn, cerulenin, chloramphenicol, tetracycline, triethyltin and triphenylmethylphosphonium bromide, but collaterally sensitive to dequalinium chloride, gentamycin, neomycin, paromomycin and thiolutin. Growth of 2-20, compared to the parental strain and 2 complete revertants, under a variety of environmental conditions revealed that strain 2-20 had an enhanced sensitivity to increased osmolality, elevated pH, and high temperature; in addition, strain 2-20 was unable to polymerize aminoimidazole ribotide at 37 degrees C as shown by the failure to develop a red colony in the presence of ade 2. Four complex solid media (glucose--KCI, galactose, ethanol, ethanol--KCI, Table 1) unable to sustain the growth of strain 2-20 were arbitrarily chosen to monitor cellular growth under different physiological conditions. Tetrad analysis indicated that the complex phenotype (cross resistance, collateral sensitivity, inablity to polymerize aminoimidazole ribotide, absence of growth under adverse physiological conditions) was inherited by an allele of a locus previously shown to result in a permeability barrier of the plasma membrane to chloramphenicol. 582 of 640 subclones used to isolate revertants of 2-20, under four different physiological conditions, were observed to produce a complete revertant of the complex phenotype. It is proposed that the pleiotropic phenotype could result from an alteration of the plasma membrane and mitochondrial inner membrane by a single nuclear gene mutation.
Mol Gen Genet 1976 Mar 30
PMID:Some physiological alteration associated with pleiotropic cross resistance and collateral sensitivity in Saccharomyces cerevisiae. 77 99

1. Four groups of rats received a liquid formula diet, given alone (control), or supplemented with either ethanol or phenobarbitone, or both together. 2. The ethanol-treated group showed a fall in plasma triglyceride and a rise in liver triglyceride, as compared with the control rats. 3. The phenobarbitone-treated group showed a marked rise in plasma triglyceride but not in liver triglyceride. 4. The group receiving both ethanol and phenobarbitone also showed a rise in plasma triglyceride, but this was accompanied by a striking increase in liver triglyceride. 5. These results suggest that ethanol and phenobarbitone each stimulate triglyceride synthesis but that in addition ethanol has an inhibitory effect on hepatic triglyceride secretion.
Clin Sci Mol Med 1977 Feb
PMID:Accentuation of ethanol-induced fatty liver by phenobarbitone. 84 54

1. We have studied activity of delta-aminolaevulinate synthase in needle liver biopsy specimens obtained from 12 human cirrhotic subjects, five subjects who had ingested anticonvulsants and from control subjects. Liver iron concentrations and quantitative urinary excretions of porphyrins plus their precursors were also determined. 2. In liver homogenates from subjects of each group, addition of an exogenous system for generation of succinyl-coenzyme A (CoA), including succinic thiokinase, resulted in appreciable enhancement of activity beyond that obtained without this system. 3. Mean activities for delta-aminolaevulinate synthease were not significantly different among patient groups when assayed without the exogenous succinyl-CoA-generating system, but liver homogenates from cirrhotic patients and subjects ingesting anticonvulsants had significantly higher activities than control subjects in the presence of the succinyl-CoA-generating system. 4. Although mean liver iron concentration in the cirrhotic group was slightly higher than in control subjects, and in control subjects there was some correlation between liver iron concentration and activity of delta-aminolaevulinate synthase, variations in this activity could not be accounted for solely on the basis of chronic hepatic deposition. Nor were these variations ascribable to differences among subjects in ingestion of ethanol before biopsy or severity of hepatic inflammation as judged biochemically and histologically. 5. Cirrhotic subjects excreted more uro- and copro-porphyrin than control subjects, whereas subjects ingesting anticonvulsants excreted more delta-aminolaevulinic acid and porphobilinogen than control subjects. However, these increases were small and not sufficient to account for all the increased delta-aminolaevulinic acid which potentially could have been formed by these subjects. 6. These considerations raise the possibilities that in vivo: (a) rate of human hepatic synthesis of delta-aminolaevulinic acid is modulated by the supply of succinyl-CoA; (b) the rate of hepatic synthesis of haem is increased in cirrhotic patients and subjects ingesting anticonvulsants; (c) other important routes exist for disposition of haem precursors in these subjects, besides utilization for haem synthesis.
Clin Sci Mol Med 1977 May
PMID:Human hepatic delta-aminolaevulinate synthase: requirement of an exogenous system for succinyl-coenzyme A generation to demonstrate increased activity in cirrhotic and anticonvulsant-treated subjects. 86 44

1. A method is described for the serial determination of renal tubular reabsorption of amino acids in the ethanol-anaesthetized rat. It utilizes intravenous radio-labelled inulins, automated amino acid analysis and forced diuresis. 2. Intravenous loading with phenylalanine and infusion of phenylalanine analogues in this preparation decrease reabsorption of endogenous amino acids in accordance with existing concepts of amino acid transport. 3. Maximal tubular reabsorption (Tmax) could not be demonstrated for phenylalanine at plasma concentration below 9 mmol/l. 4. Infusion of phenylalanine analogues into phenylalanine-loaded ('phenylketonuric') rats did not specifically inhibit tubular reabsorption of phenylalanine and it is unlikely that any of the substances tested have a potential therapeutic use in man. 5. p-Guanidino derivatives of phenylalanine, in contrast to p-amino derivatives, appear to cause a dose-related basic aminoaciduria. 6. Consideration of urinary flow rates and sodium excretion suggests that the ethanol anesthesia does not modify amino acid reabsorption through effects on sodium transport or antidiuretic hormone.
Clin Sci Mol Med 1977 Oct
PMID:Effects of phenylalanine analogues on renal tubular reabsorption of amino acids in the rat. 91 60

1. A method for extraction, partial purification and radioimmunoassay of angiotensin II in tissues and application of the method to the kidneys of sodium-deficient rats are described. 2. Angiotensin in acid-ethanol extracts of kidney were adsorbed on to a cation-exchange resin, eluted and further purified with an immobilized angiotensin II antiserum, before radioimmunoassay. 3. Thin-layer chromatography was used, in some experiments, to separate fmol amounts of angiotensin II from its immunoreactive peptide fragments before radioimmunoassay. 4. Angiotensin II-immunoreactive material isolated from rat kidney resembled angiotensin II in many of its physicochemical properties and chromatographic mobility. 5. The concentration of immunoreactive material in kidney greatly exceeded that which could be accounted for by trapped blood and suggests that the peptide may have a local role in the organ.
Clin Sci Mol Med 1976 Aug
PMID:A method for measurement of angiotensin II in tissues and its application to rat kidney. 95 57


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