Glycoproteins life-time

EoUowing po administration moricizine is completely absorbed from the GI tract. The dmg undergoes considerable first-pass hepatic metabolism so that only 30—40% of the dose is bioavailable. Moricizine is extensively (95%) bound to plasma protein, mainly albumin and a -acid glycoprotein. The time to peak plasma concentrations is 0.42—3.90 h. Therapeutic concentrations are 0.06—3.00 ]l/niL. Using radiolabeled moricizine, more than 30 metabolites have been noted but only 12 have been identified. Eight appear in urine. The sulfoxide metabolite is equipotent to the parent compound as an antiarrhythmic. Elimination half-life is 2—6 h for the unchanged dmg and known metabolites, and 84 h for total radioactivity of the labeled dmg (1,2). 

The role of sialic acid residues in determining the life-time of circulating cells and glycoproteins and the importance of desialylation have been discussed, Chromatography on Blue Dextran 2000 coupled to agarose has been used in the rapid separation of factor X from citrated human plasma a 2(XX)-fold purification was achieved, Inhibition by the antithrombin-heparin cofactor of the conversion of factor IX into its active form by factor IXa has been examined. The process is time-dependent and requires a 1 1 combination... 

High-density lipoproteins (HDL) have much longer life spans in the body (5 to 6 days) than other lipoproteins. Newly formed HDL contains virtually no cholesterol ester. However, over time, cholesterol esters are accumulated through the action of lecithin cholesterol acyltransferase (LCAT), a 59-kD glycoprotein associated with HDLs. Another associated protein, cholesterol ester transfer protein, transfers some of these esters to VLDL and LDL. Alternatively, HDLs function to return cholesterol and cholesterol esters to the liver. This latter process apparently explains the correlation between high HDL levels and reduced risk of cardiovascular disease. (High LDL levels, on the other hand, are correlated with an increased risk of coronary artery and cardiovascular disease.)... 

Coagulation factors are glycoproteins named by roman numbers (the numbers being ascribed at the time of the components definition, not sequence of activation) (Table 1). Besides von Willebrand factor (vWF), the coagulation factors are synthesized in the liver. They have very different half-lifes and different concentrations in the plasma. Several coagulation factors are stored in platelets and endothelial cells and can be released during activation of these cells, which can result in a much higher local concentration of the respective factor (e.g., vWF). 

Zanamivir (2) is a potent competitive inhibitor of viral neuraminidase glycoprotein, which is essential in the infective cycle of both influenza A and B viruses. It inhibits a wide range of influenza A and B types in vitro as well as in vivo. The concentrations of inhibiting in vitro plaque formation of influenza A and B virus by 50% in Madin-Darby canine kidney (MDCK) cells were 0.004-0.014 p.mol/L in laboratory-passaged strains, and 0.002-16 p.mol/L in assays of clinical isolates. Due to its low bioavailability, it is delivered by inhalation via the Diskhaler , 10 mg twice daily, or intranasally 2-4 times daily for 5 days. After an intravenous dose of 1 -16 mg, the median elimination half-life was ti/2 = 7 h, the volume of distribution at steady state was Vdss = 16 L, and 90% of the dose was excreted unchanged in the urine. After intranasal and inhaled (dry powder) administration, maximum serum concentrations occurred within 2h and the terminal phase half-lives were 3.4 and 2.9 h, respectively. The bioavailabilities were 10 and 25%, respectively, and 20% after inhalation of zanamivir (2) by nebulizer. 

The essential roles, although controversial at times, played by both of these surface glycoproteins in the infectious life cycle of the virus, coupled with a... 

In the plasma membranes of rat liver the higher gangliosides GT ib, GD la, and GDib are degraded with a half-life of about 48 hrs, while GM3-bound sialic acid did not show any degradation at all (in the time-interval of 12 to 72 hrs after injection of the radioactive labeled precursor N-acetylmannosamine) (Hafermaas et al. 1982). Similar results have been obtained from studies on the turnover of plasma membrane glycoproteins (Kreisel et al. 1980, Tauber et al. 1982). This... 

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