Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When initial velocities are measured with yeast hexokinase at pH 7, 17 degrees, the inert coordination complex chromium-ATP is competitive vs. MgATP and noncompetitive with glucose, with a dissociation constant of 4-6 muM in either the presence or absence of glucose. These patterns confirm a random kinetic mechanism for this enzyme. With CrATP present, however, the reaction slows down over the first several minutes to a much slower rate, suggesting tighter binding of CrATP with time. When CrATP, MgATP, and D-lyxose are preincubated with the enzyme for 10 min and the reaction started by addition of excess glucose, the dissociation constand of CrATP in now 0.13 muM and the reaction is linear with time. When glucose, CrATP, and enzyme are incubated together and then placed on a Sephadex column, 1 mol each of CrATP and glucose per active center is tightly bound to the enzyme, thus providing a simple and precise method of determining the concentration of active sites. This tight complex, after denaturation with acid, releases 25% free glucose and 75% of a chromium complex containing both ADP and sugar-6-P. CrADP-glucose-6-P is also slowly released from the enzyme during incubation, so that CrATP is actually a very slow substrate. Binding of CrATP with the formation of CrADP-sugar-6-P complexes is also induced by mannose, fructose, glucosamine, 2,5-anhydro-D-glucitol, 2,5-anhydro-D-mannose, and 2,5-anhydro-D-mannitol, while glucose-6-P, 6-deoxyglucose, and lyxose also induce tight binding of CrATP. With excess enzyme, only 25% of CrATP is bound, and the rest does not inhibit the hexokinase reaction. Since bidentate Cr(NH3)4ATP and monodentate CrADP also display inhibition which is tighter with time, but since bidentate CrADP is a poor inhibitor, the actural substrates in the hexokinase reaction appear to be beta, gamma-bidentate MgATP and beta-monodentate MgADP. Tighter inhibition by Cr-8-BrATP than by CrATP suggests that ATP ASSUMES THE SYN CONFORMATION ON THE ENZYME. The substrate inhibition by MgATP induced by the presence of lyxose is shown to be competitive vs. glucose and partial, and, together with other data available, to suggest a kinetic mechanism that is random, but where (1) the rate constant for release of glucose from E-glucose is equal to Vmax, and that for release of glucose from central complexes is less than Vmas; (2) the majority of the reaction flux when both substrates are present at Km levels goes through the path with glucose adding before MgATP, but where at physiological levels the flux through the two paths is more equal. Contd.
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PMID:Use of chromium-adenosine triphosphate and lyxose to elucidate the kinetic mechanism and coordination state of the nucleotide substrate for yeast hexokinase. 108 14

Galanin (GAL), a 29 amino acid neuropeptide, is known to increase both basal and growth hormone-releasing hormone (GHRH)-induced growth hormone (GH) secretion while not significantly increasing prolactin (PRL) secretion in man. GAL is also endowed with an inhibiting effect on glucose-stimulated insulin release in animals, but not in man. We studied the effect of GAL (80 pmol/kg/min infused over 60 minutes) on the arginine- (ARG, 30 g infused over 30 minutes) stimulated GH, PRL, insulin, and C-peptide secretion in eight healthy volunteers (age, 20 to 30 years). GAL induced an increase of GH (GAL v saline, area under curve [AUC], mean +/- SEM: 316.5 +/- 73.9 v 93.2 +/- 20.9 micrograms/L/h, P less than .05), but failed to modify both PRL and insulin secretion. GAL enhanced the ARG-induced stimulation of both GH (1,634.1 +/- 293.1 v 566.9 +/- 144.0 micrograms/L/h, P less than .02) and PRL secretion (1,541.9 +/- 248.8 v 1,023.8 +/- 158.7 micrograms/L/h, P less than .02). On the contrary, GAL blunted the ARG-stimulated insulin (816.3 +/- 87.7 v 1,322.7 +/- 240.9 mU/L/h, P less than .05), as well as C-peptide secretion (105.1 +/- 9.8 v 132.8 +/- 17.3 micrograms/L/h, P less than .02). ARG administration induced a transient increase of glucose levels (P less than .01 v baseline) followed by a significant decrease (P less than .05 v baseline). This latter effect was prevented by the coadministration of GAL. In conclusion, these results show that in man GAL potentiates the GH response to ARG, suggesting that these drugs act at the hypothalamic level, at least in part, via different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions of galanin and arginine on growth hormone, prolactin, and insulin secretion in man. 137 76

We have previously shown that normal Wistar rats fed for 3 weeks with an isocaloric sucrose-rich (63%) diet (SRD) develop high levels of plasma free fatty acids and increased triacylglycerol content in the myocardium. We are now reporting that these changes are accompanied by remarkably low levels of the active form of the pyruvate dehydrogenase complex (PDHa; mean +/- SEM, 37.2% +/- 3.7% of the total activity) when compared with levels found in hearts donated by control rats fed the standard chow diet (STD; 71.0% +/- 2.8%; P less than .01). Increased concentrations of both long-chain acyl-CoA (0.21 +/- 0.03 v 0.06 +/- 0.01 mumol.g dry weight-1 found in STD; P less than .01) and acetyl-CoA (0.17 +/- 0.05 v 0.09 +/- 0.01 found in STD; P less than .01), as well as a relative decrease in coenzyme A (CoASH) (0.21 +/- 0.02 v 0.32 +/- 0.05 from STD; P = NS), resulting in an increased acetyl-CoA/CoASH ratio (0.80 +/- 0.13 v 0.29 +/- 0.03 in STD; P less than .01) may have stimulated the PDH kinase, leading in turn to an inactivation of the PDH complex. The above enzymatic and metabolic changes in the in situ heart of SRD-fed rats were still present after perfusing them for 35 minutes with a Krebs-Henseleit buffer containing 11 mmol/L glucose as the only exogenous substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical abnormalities in the heart of rats fed a sucrose-rich diet: is the low activity of the pyruvate dehydrogenase complex a result of increased fatty acid oxidation? 198 63

Radiolabeled fluoromisonidazole (FMISO) is being investigated as an imaging agent for hypoxia in tumors and nonmalignant tissues in myocardial infarct or stroke. In this study in vitro cell cultures were used to characterize the oxygen dependency of FMISO uptake and to examine other modifying factors. The uptake of [3H]FMISO was measured in four cell lines in vitro: V-79, EMT-6(UW), RIF-1, and CaOs-1. The modifying effects of different O2 levels as well as cell growth state and concentration of glucose and nonprotein sulfhydryls were examined. In these cell types an O2 level between 720 and 2300 ppm inhibited FMISO binding by 50%, relative to binding under anoxic conditions. These values bracket the O2 level which confers full radiobiologic hypoxia, about 1000 ppm. Some bound label was released from cells in the first 1 to 3 h after a 3-h anoxic labeling with [3H]FMISO, but this does not represent tritium loss from the parent molecule. Cells from unfed plateau-phase cultures took up less [3H]FMISO than did exponentially growing cells incubated at comparable O2 levels. Reducing glucose to 1/10 or 1/100 of the usual concentration in medium had little effect on binding of micromolar levels of FMISO, except in V-79 cells, where reduced glucose levels were associated with increased FMISO accumulation. Adding cysteamine to the culture medium moderately increased FMISO uptake. We conclude that cell growth state, glucose, and nonprotein sulfhydryl concentrations affect FMISO binding, albeit less than varying O2 levels: anoxic/oxic binding ratios vary from 12.6 to 28 for the four cell types examined. Nonetheless these factors must be considered in evaluating the oxygen-dependent binding of this nitroimidazole in tumors or tissues.
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PMID:Characteristics of the binding of labeled fluoromisonidazole in cells in vitro. 235 84

In recent years, laboratory testing in the critical-care setting has increased, a trend due, in part, to the evolution of electrochemical sensors. Various innovations have extended sensor lifetimes, reduced sensor maintenance, and led to the development of single-use and unit-use disposable sensors. These sensor technologies allow the accurate and precise determination, either at or near the bedside, of several analytes including pO2, pCO2, pH, Na, K, Cl, ionized calcium, hematocrit, total hemoglobin, and glucose. Use of these new systems, however, has raised new issues regarding sensor calibration and sample handling and collection. The number of direct-reading analyzers for electrolyte determinations has also increased dramatically. Issues regarding calibration of ion-selective electrodes (ISEs) for Na/K have also been raised after demonstrations of between-instrument variation. Recently, collaborative efforts between eight ISE instrument manufacturers and the National Institute of Standards and Technology resulted in the development of a Standard Reference Material, SRM 956, for the purpose of standardizing direct-reading Na/K ISEs to the flame photometer. Other widely used technologies that provide noninvasive, continuous monitoring include pulse oximetry and transcutaneous gas electrodes. These trends are expected to continue and to produce a new generation of electrochemical and optical sensors.
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PMID:Current analytical approaches to measuring blood analytes. 238 68

Severe heat stress experienced by aircrew during summer months can cause deterioration in performance. Acute heat stress can also lead to dehydration and loss of electrolytes. Previous studies emphasised the need of K+ replacement. This study was carried out to determine the effect of glucose electrolyte ingestion (ELECTRAL) on thermal strain parameters. Ten healthy male subjects in the age group of 19-43 years were exposed to an acute thermal environment of 50 degrees C Tdb with relative humidity of 30% for 40 min. twice each day on two different days with an interval of one hour in between the exposures. At the beginning of rest period electrolyte solution was ingested during electrolyte trials and water under control trials. Physiological parameters of Tsk, T or, HR and electrolyte concentration of Na+ and K+ in sweat did not show any significant difference in both the trials. Sweat loss was significantly higher during electrolyte trials.
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PMID:Effect of glucose electrolyte ingestion on physiological changes due to severe heat stress. 259 41

Broiler-breeder females from a parent stock segregating for early and late feathering were fed ad libitum (AL, feed was always available), ad libitum restricted (ALR, feed restricted daily to control body weight), skip-one-day and skip-two-days (SOD and STD, given two or three times ALR allowance on Day 1 and not fed on the next 1 or 2 days, respectively). At 160 days of age, pullets on SOD and STD were changed to ALR feeding, and daily feed allowances were increased to 135 g by Day 180 and 138 g by Day 250. Responses of early and late-feathering females were similar for traits measured. Generally, body weights of AL chickens increased to 4,600 g at 130 days of age and then reached a plateau. Body weights of feed-restricted groups were less than half of that of AL chickens by 160 days of age. Controlled release from feed restriction enabled chickens to reach a weight of approximately 3,200 g by Day 210. Daily feed consumption for AL chickens increased to about 220 g by 140 days of age and then decreased to approximately 150 g by Day 250; it eventually decreased to approximately 120 g by Day 350, where it reached a plateau. Mortality, plasma glucose levels, and surface and cloacal temperatures were lower for females whose feed was restricted than for those fed AL. Plasma protein levels were greater for STD than for AL, ALR, and SOD groups whereas plasma lipids were higher for AL and SOD than for ALR and STD groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Restricted feeding in early and late-feathering chickens. 1. Growth and physiological responses. 270 91

This study compared the effects of ingesting 6% (MC) and 12% (HC) glucose/electrolyte beverages, and a flavored water placebo (P) on markers of fluid absorption, palatability, and physiological function during prolonged intermittent cycling in the heat. On three occasions, 15 trained male cyclists performed two 60 min cycling bouts at 65% VO2max (E1 and E2). A brief exhaustive performance ride (approximately 3 min) was completed after E1 and E2, and after 20 min recovery (P1, P2, P3). Every 20 min, subjects consumed 275 mL of P, MC or HC. The first drink contained 20 mL of D2O, a tracer of fluid entry into blood plasma. Plasma D2O accumulation was slower for HC than for P and MC (P less than 0.001). HC caused more nausea (P less than 0.01) and fullness (P less than 0.05) than MC or P, and subjects said they would be less likely to consume HC during training or competition (P less than 0.10). Sweat rates, HR, Tre, Tsk, VO2, and PV were similar for all drinks. Performance of P1, P2, P3 were not different among drinks. However, four cyclists failed to maintain the prescribed work rate during E2 for HC but only one failed for MC and P. These data suggest that the slow absorption of a 12% glucose/electrolyte beverage during prolonged intermittent exercise in the heat may increase the risk of gastrointestinal distress and thereby limit performance.
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PMID:Effects of ingesting 6% and 12% glucose/electrolyte beverages during prolonged intermittent cycling in the heat. 339 73

Effects were compared of two methods of feed restriction (skip-a-day, SAD, vs. skip-two-days, STD) during 4 to 22 wk of age on the development, uniformity, and subsequent performance of White Rock pullets. The pullets, housed in cages, consumed the same amount of feed in both treatments. Nevertheless, body weights of birds kept under the STD feeding regimen were significantly (P less than .01) lower. This difference was still significant (P less than .05) at 35 wk of age. Flock uniformity at 11 wk of age was significantly (P less than .05) higher in pullets kept on the STD feeding program. Plasma glucose and corticosterone levels in fasted pullets and corticosterone levels in fed birds at the age of 21 wk were not affected by feeding regimen. However, the increase in plasma glucose after feeding was significantly (P less than .05) higher in pullets on the STD feeding program. Plasma corticosterone levels were consistently, and at times significantly (P less than .05), higher in fasted birds. Laying of the first egg was significantly (P less than .05) delayed in hens previously kept on the STD feeding regimen. Rate of egg production and egg weights up to 35 wk of age were not affected by the method of feed restriction.
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PMID:Feed restriction in broiler breeder pullets: skip-a-day versus skip-two-days. 340 57

With respect to liver disease, the primary function of the laboratory is to identify its presence. Tests are not available that permit a specific diagnosis and an accurate prognosis. Several tests should be present in a minimum data base that can help identify hepatobiliary disease. They are ALT, SAP, total serum bilirubin, urine bilirubin, cholesterol, albumin, BUN, glucose, red cell morphology, and urine sediment. It is sometimes possible to tentatively identify whether a disease is primarily hepatocellular or biliary from the pattern of changes that occur in these tests. In addition, an estimate of the severity is sometimes possible when abnormal values are extreme. The keys are to avoid overinterpretation, use serial evaluations, and rely on a liver biopsy when definitive answers are needed. If liver disease is suspected but there are only marginal changes in the routine tests, the more sensitive tests of function, BSP retention and ammonia tolerance, are warranted. In the future, as more knowledge is gained about the responses of ARG, GGT, and ICG retention to naturally occurring diseases, these tests may join or replace some of those currently used. Also, as the ability to accurately and economically measure the various bile acids improves, a sensitive, yet noninvasive, method to detect and define modest changes in hepatobiliary function may result.
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PMID:Laboratory evaluation of liver disease. 387 5


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