Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brief starvation is accompanied by decreased circulating levels of most amino acids, which has been attributed to an increased splanchnic uptake of amino acids, primarily alanine, for gluconeogenesis. However, quantitative data on splanchnic exchange of amino acids and gluconeogenic precursors is lacking. Consequently, arterial concentrations and splanchnic exchange of whole blood amino acids, ketone bodies, glucose, and gluconeogenic precursors were measured in 16 prolonged fasted (60 to 64 hours) and 15 overnight fasted (12 to 14 hours) healthy, nonobese subjects. After the 60-hour fast net splanchnic glucose production decreased by 41% to 0.31 +/- 0.02 mumol/L (P less than .001), whereas the splanchnic uptake of gluconeogenic precursors increased and could account for the total glucose output. Net splanchnic uptake of taurine, threonine, serine, glycine, lysine, histidine, and arginine rose significantly in response to fasting (P less than .05 to .01) due to increased splanchnic fractional extraction. Although the splanchnic fractional extraction of alanine was augmented by 40% (P less than .001), net splanchnic uptake was not influenced by fasting. Total net splanchnic uptake of amino acids increased by 68%, from 231 +/- 44 mumol/min in the postabsorptive state to 388 +/- 63 mumol/min (mean +/- SEM) (P less than .05) in the 60-hour fasted state. However, only one half of this rise was accounted for by gluconeogenic amino acids.
 ...
PMID:Splanchnic metabolism of amino acids in healthy subjects: effect of 60 hours of fasting. 319 1

Semisynthetic human insulin is prepared from porcine pancreas by chemical methods involving the substitution of porcine B-30 alanine with threonine. To compare the effectiveness of porcine and semisynthetic human insulins, eight insulin-dependent diabetic patients were evaluated during two separate periods using a glucose-controlled insulin infusion system. During each 36-h period, patients received either porcine or semisynthetic human insulin. Patients ingested mixed meals. The mean daily insulin requirements for porcine and semisynthetic human insulins were 84 +/- 9 U and 85 +/- 6 U (+/- SEM), respectively (P = NS). Mean blood glucose values were similar at 95 +/- 1 mg/dl for porcine and 101 +/- 3 mg/dl with semisynthetic human insulin (P = NS). Prior metabolic control or insulin antibody levels did not correlate with intravenous insulin requirements. These studies indicate that semisynthetic human insulin is as effective as porcine insulin in maintaining near-normal blood glucose control in short-term intravenous studies using artificial pancreas techniques in insulin-dependent diabetes.
 ...
PMID:Comparison of the biologic activity of porcine and semisynthetic human insulins using the glucose-controlled insulin infusion system in insulin-dependent diabetes. 634 25

The effects of a 4-day isocaloric isoprotenic dietary replacement of carbohydrate by fats were studied in six healthy subjects, the experimental diet being preceded and followed by a 3-day period of balanced diet. During the ketogenic regimen, the concentrations of fat derived substrates (free fatty acids, glycerol and 3-hydroxybutyrate) rose significantly and glucose levels decreased by 16.5 +/- 3.2% (mean +/- SEM). The hormonal pattern switched towards a catabolic mode with a fall in insulin levels (-44.0 +/- 6.3%) and a rise in glucagon concentration (+39.0 +/- 10.4%). A significant fall in triiodothyronine and rise in reverse triiodothyronine were observed, while thyroxine levels remained unchanged. The average levels of the most important gluconeogenic amino acids (alanine, glutamine, glycine, serine and threonine) were reduced by 8-34% while those of the branched chain amino acids increased by more than 50%. Since these changes reproduce those observed after a few days of total fasting, we suggest that it is the carbohydrate restriction itself which is responsible for the metabolic and hormonal adaptations of brief fasting.
 ...
PMID:Hormonal and metabolic changes induced by an isocaloric isoproteinic ketogenic diet in healthy subjects. 676 Nov 85

Ninety-five female pigs from 20 to 45 kg body weight were used to elucidate the effects of energy and protein intake on the amino acid composition of the protein in the carcass, organs and empty body of growing pigs. In a 2 x 15 factorial arrangement, protein intake ranged from 127 to 350 g/d in 15 graduated steps; and the digestible energy allowances were 15.8 and 18.8 MJ/d. Whole-body amino acid contents (g/16 g nitrogen) were (means +/- SEM) lysine 6.64 +/- 0.028, methionine 2.11 +/- 0.012; threonine 3.62 +/- 0.016 and total essential amino acids 42.8 +/- 0.16. The organ fraction contained 14.8 and 15.8% (SEM 0.13) of whole-body protein at the low and high energy levels, respectively. The concentrations of essential amino acids were 41.8 +/- 0.19 and 48.4 +/- 0.13 g/16 g nitrogen in the carcass and organs, respectively. Concentrations of a number of amino acids (in carcass, organ and whole-body protein and in protein deposited between 20 and 45 kg, were affected by protein and/or energy intake. The amino acid pattern of the newly deposited protein was slightly different from that of the empty body protein. The changes in amino acid contents were presumably the result of effects of protein and energy intake on the proportions of muscle and non-muscle carcass tissues and on relative weights of blood and viscera. Consequences of these changes for the amino acid requirements are discussed.
 ...
PMID:Amino acid composition of growing pigs is affected by protein and energy intake. 793 5

rt-PA-K, a variant of recombinant tissue-type plasminogen activator (rt-PA) with substitution of amino acids 296 to 299 with alanine (KHRR296-299AAAA) has increased fibrin-specificity and reduced sensitivity to plasminogen activator inhibitor-1; rt-PA-T, with threonine 103 replaced by asparagine has an additional glycosylation site and a reduced clearance; and rt-PA-N, with asparagine 117 mutagenized to glutamine lacks the high mannose carbohydrate side chain. We have investigated whether combination of these properties in a single molecule might yield an improved thrombolytic agent. The thrombolytic potency and fibrin-specificity of the combination mutant rt-PA-TNK was compared with that of rt-PA in a combined venous whole blood clot model and platelet-rich arterial eversion graft thrombosis model in dogs given intravenous heparin and aspirin. Infusion of 0.125 to 1.0 mg/kg over 60 min in groups of 4 to 5 dogs produced dose-dependent fibrin-specific venous clot lysis. The thrombolytic potency (percent lysis per mg compound administered per kg body weight) of rt-PA-TNK was significantly higher than that of rt-PA as evidenced by a higher maximal rate of lysis of 480 +/- 100% versus 140 +/- 40% within the 2 h observation period per mg of compound administered per kg body weight (mean +/- SEM, p = 0.004) and a significantly lower dose of 0.08 +/- 0.01 versus 0.21 +/- 0.04 mg/kg body weight at which the maximal rate of lysis was obtained (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparative thrombolytic properties of tissue-type plasminogen activator and of a plasminogen activator inhibitor-1-resistant glycosylation variant, in a combined arterial and venous thrombosis model in the dog. 797 84

Two experiments were conducted to determine the utilization of ileal digestible isoleucine by growing pigs. In the first, the apparent ileal digestibility of amino acids in cottonseed meal, lupin-seed meal and soya-bean meal was determined in pigs fitted with 'T'-shaped cannulas. In the second, three isoleucine-deficient diets were formulated to 0.23 g ileal digestible isoleucine/MJ digestible energy (DE) with the three protein concentrates contributing the only source of isoleucine in sucrose-based diets. An additional three diets were formulated with supplements of isoleucine to confirm that isoleucine was limiting in the first three diets. The growth performance and retention of isoleucine by pigs given the six diets over the 20-45 kg growth phase were then determined. The apparent ileal digestibility of isoleucine in the three protein concentrates (proportion of total) was: cottonseed meal 0.68, lupin-seed meal 0.86, soya-bean meal 0.86. There were no significant differences (P > 0.05) in growth rates (g/d) and crude protein deposition rates (g/d) of the pigs given the three diets formulated to 0.23 g ileal digestible isoleucine/MJ DE: cottonseed meal 590, 84; lupin-seed meal 613, 87; soya-bean meal 594, 91 (SEM 13.0, 2.9) respectively. The response of pigs to the addition of isoleucine confirmed that isoleucine was limiting in these diets. The proportion of ileal digestible isoleucine retained by pigs given the cottonseed meal (0.65) was slightly lower than that retained by pigs given soya-bean meal (0.73; P < 0.05). These results indicate that values for the ileal digestibility of isoleucine in protein concentrates more closely reflect the proportion of isoleucine that can be utilized by the pig than occurs for other amino acids such as lysine, threonine and methionine.
 ...
PMID:Utilization of ileal digestible amino acids by growing pigs: isoleucine. 801 6

Ileal and fecal gut endogenous nitrogen and amino acid excretions in adult domestic cats were determined. Ileal digesta were collected (10 cm of terminal ileum) from the cats fed either a protein-free diet or an enzymatically hydrolyzed casein-based diet (free amino acids and peptides < 10,000 Da) for 1 wk. Chromic oxide was included in each diet as an indigestible marker. The relative contribution of the hindgut to total endogenous gut excretion was investigated in a separate study by feeding cats a protein-free diet with or without added antibiotics for 10 d. Endogenous ileal nitrogen and amino acid nitrogen excretions of (mean +/- SEM 2.4 +/- 0.27 and 1.9 +/- 0.13 mg/g food dry matter intake, respectively, were found for the cats fed the protein-free diet, whereas higher excretions of 3.6 +/- 0.73 (P = 0.12) and 3.6 +/- 0.76 (P = 0.03) mg/g food dry matter intake were obtained in cats fed the enzymatically hydrolyzed casein. Significantly (P < 0.05) higher endogenous ileal amino acid excretions, for the enzymatically hydrolyzed casein-fed cats compared with those fed the protein-free diet, were found for methionine, aspartic acid, serine, glutamic acid, proline, valine and isoleucine, with the differences in excretions of glycine, alanine, leucine and histidine being significant at the 6% level. Most of the endogenous fecal amino acid excretions were unaffected by the inclusion of the antibiotics in the protein-free diet, although bacterial numbers were significantly lower (69%). Antibiotics addition led to significantly higher fecal endogenous excretions of nitrogen, taurine, threonine, serine and histidine but significantly lower excretions of methionine and lysine. Cats, like other simple-stomached mammals, excrete higher amounts of endogenous amino acids at the terminal ileum when the diet contains peptides.
 ...
PMID:Gut endogenous nitrogen and amino acid excretions in adult domestic cats fed a protein-free diet or an enzymatically hydrolyzed casein-based diet. 861 99

In cells, insulin stimulates autophosphorylation of the insulin receptor on tyrosine and its phosphorylation on serine and threonine by poorly characterized kinases. Here we describe methods for the purification of an insulin-stimulated insulin receptor serine kinase from human placenta and rat liver by sequential chromatography of solubilized membranes on wheat germ agglutinin-agarose, Mono Q, phenyl-Superose, and Superose 12. On silver-stained SDS-polyacrylamide gels, the resulting kinase was homogeneous (human) or near-homogeneous (rat) and had an apparent M(r) of 40000. The apparent M(r) determined by gel filtration was also 40000, suggesting that the kinase exists as a monomer. The kinase could be reconstituted back to the insulin receptor stripped of the kinase to yield a high stoichiometry of serine phosphorylation of the insulin receptor in the presence of insulin (0.75 +/- 0.15 mol/mol of beta-subunit, mean +/- SEM, n = 3). The activity of the reconstituted kinase toward the insulin receptor was insulin-regulated, being stimulated > 5-fold by insulin. Insulin increased the catalytic activity of the reconstituted kinase. The purified kinase specifically phosphorylated serine 1078 of the insulin receptor, a major site of insulin-stimulated serine phosphorylation in vivo, showing that the purified kinase phosphorylated a physiologically relevant site on the insulin receptor. Phosphorylation of serine 1078 of the insulin receptor to high stoichiometry by the kinase did not affect insulin-stimulated exogenous protein tyrosine kinase activity of the insulin receptor. Similarly, insulin receptor phosphorylated with or without the purified kinase exhibited the same levels of tyrosine autophosphorylation and of the tyrosine kinase-activating tris-phosphorylated kinase domain species. Properties of the kinase distinguished it from kinases known to act on the insulin receptor and other kinases that are insulin-stimulated, indicating that the kinase is a novel entity. The serine kinase underwent autophosphorylation on serine and immunoprecipitated with the insulin receptor. The availability of the purified kinase should facilitate cloning of the kinase, determination of the mechanism of activation of the kinase, and study of the wider potential role of the kinase in insulin signalling, and the ability to be able to phosphorylate serine 1078 to high stoichiometry should facilitate further studies into the function of this serine phosphorylation site.
 ...
PMID:Purification and characterization of an insulin-stimulated insulin receptor serine kinase. 891 21

Studies performed over the past several years have provided evidence that phosphorylation of proteins is important in the regulation of neurotransmitter release. In this study, it is shown that rabphilin-3A is present in cerebellar granule cells as a phosphoprotein, by using 32P-labeling of cerebellar granule cells, immunoprecipitation, phosphoamino acid analysis, and phosphopeptide mapping. The level of phosphorylation was increased (224 +/- 13%) (mean +/- SEM) on depolarization of the cells with K+ (56 mM) in the presence of external Ca2+ (1 mM). Stimulation of protein kinase C with a phorbol ester (phorbol 12,13-dibutyrate) also enhanced the phosphorylation of rabphilin-3A (217 +/- 21%). Inhibitors of Ca2+/calmodulin-stimulated protein kinases or protein kinase C reduced the depolarization-enhanced phosphorylation of rabphilin-3A, indicating that rabphilin-3A is one of the targets for Ca2+-activated protein kinases in the nerve terminal. Costimulation of cells with phorbol 12,13-dibutyrate and K+ depolarization produced an increased level of phosphorylation of rabphilin-3A compared with either stimulus alone (287 +/- 61%). Phosphoamino acid analysis showed that serine was the main phosphorylated residue. A slight increase in the threonine phosphorylation could also be detected, whereas tyrosine phosphorylation could not be detected at all. These results suggest that rabphilin-3A is phosphorylated in vivo and undergoes synaptic activity-dependent phosphorylation during Ca2+-activated K+ depolarization.
 ...
PMID:Depolarization of cerebellar granule cells increases phosphorylation of rabphilin-3A. 975 Dec

Thrombospondin 1 (TSP-1), an adhesive glycoprotein, plays an important role in platelet adhesion, inflammation, cell-cell interaction, and angiogenesis. TSP-1 is expressed by endothelial cells, fibroblasts, and macrophages. The unique cysteine-serinevaline-threonine-cysteine-glycine (CSVTCG) binding domain of TSP-1 also plays an important role in cell binding and modulation of cellular processes. The purpose of this study was to evaluate histologically and quantitatively TSP-1 and its CSVTCG receptor in fetal skin wounds over time. Pregnant ewes underwent laparotomy and hysterotomy. At 65 days gestation (term, 145 days), incisional and excisional wounds were created on the fetal back in a similar position on each animal. The uterus and laparotomy were closed. The wounds were harvested on days 1, 3, 7, 21, and 28. Expression of TSP-1 and its CSVTCG receptor was evaluated immunohistochemically and quantitated by computer image analysis in units of absorbance. Immunoglobulin G (negative) controls were performed and subtracted from the TSP-1 sample to eliminate background absorbance readings. Serum (negative) control was used for the CSVTCG receptor. Platelet concentrates were used as the positive control: TSP-1, 63.43; CSVTCG, 58.72. Results are expressed as absorbance+/-SEM. Results of TSP-1 are as follows: day 1, 33.02+/-0.26; day 3, 22.21+/-0.14; day 7, 20.56+/-1.07; day 21, 7.76+/-0.40; and day 28, 5.99+/-0.03. TSP-1 displays an early peak during fetal skin repair, followed by a steep decrease over the viewed time period. Results of CSVTCG receptor are as follows: day 1, 26.19+/-2.43; day 3, 30.20+/-0.64; day 7, 24.56+/-0.80; day 21, 24.70+/-0.40; and day 28, 21.65+/-1.39. Thus, CSVTCG receptor displays a slowed decrease in expression over time during fetal repair. No significant differences were noted between incisional and excisional samples. Temporal and histological differences exist in the localization and expression of TSP-1 and its CSVTCG receptor during fetal wound repair. TSP-1 is upregulated in tissues early. This corresponds with the known role of TSP-1 in cell-cell interaction, including potentiation of growth factor activity. TSP-1 also modulates matrix, allowing scar-free provisional matrix in the earlier stages of repair deposited by platelets. The potentiation of cell-associated protease activity by TSP-1 can support tissue and matrix turnover. This activity of TSP-1 may contribute to the formation of a scarless wound. TSP-1 destabilizes extracellular matrix contacts, and facilitates mitosis and migration. The action of TSP-1 as an adhesive protein allows numerous different cells to adhere to the extracellular membrane. CSVTCG receptor expression decreases during fetal repair as the cells migrate to the epithelial surface, suggesting a significant role of the CSVTCG receptor in keratinocytic maturation, differentiation, and epithelization.
 ...
PMID:Thrombospondin 1 and its specific cysteine-serine-valine-threonine-cysteine-clycine receptor in fetal wounds. 1034 Aug 67


1 2 Next >>