Catabolism protein activators

The concept of the catabolism of glycosphingolipids by glycohydro-lases has entered a new era with the discovery of protein activators, but there are many questions remaining to be answered. What is the physiological role of the activators What is the mode of their action ... 

Some proteins activate transcription by directly contacting RNA polymerase. For example, cyclic AMP, a hunger signal, stimulates the transcription of many catabolic operons by binding to the catabolite activator protein. The binding of the cAMP—CAP complex to a specific site in the promoter region of an inducible catabolic operon enhances the binding of RNA polymerase and the initiation of transcription. 

One of the best efforts to compare the anabolic activity of many steroids which have been discussed is that of Albanese and coworkers (1), who devised a careful means of comparing a wide series of steroids. They employed nitrogen balance studies in appropriate patients. They then expressed the steroid protein activity index, the SPAI, on a comparative basis. The antianabolic or catabolic adrenal cortical steroids all have negative values by this assay. Table II shows comparative SPATs of seven of the steroids which have been discussed. It can be seen by this index that testosterone propionate is the least active and stanozolol the most active. Further reports from Albanese and coworkers will be anticipated with interest. 

Catabolic Gene-Activator Protein (CAP) Positively Regulates the lac Operon... 

A stimulus which alters the steady-state level of an endogenous cellular component may do so by influencing its rate of synthesis, its rate of break-down, or both. When administered to intact animals, phenobarbital or 3-methylcholanthrene increase (20-50%) the steady-state level of microsomal protein. Similarly, micro-somes from animals pretreated with phenobarbital or 3-methylcholanthrene incorporate radioactive amino acids into protein more rapidly than microsomes from control animals and this effect is blocked by co-administration of actinomycin-D. It was therefore assumed that the increased levels of microsomal protein and enzyme activity after inducers were the result of enhanced synthesis. However, turnover studies have revealed that phenobarbital in particular has a profound effect upon microsomal protein catabolism. Proteins of the endoplasmic reticulum were labelled by injection of radioactive amino acids and the rate at which radioactivity disappeared from the microsomes was compared in control and phenobarbital-treated animals. Assuming a comparable degree of isotope re-utilization in the two groups, this approach provides a relative measure of microsomal-protein turnover. In control animals, radioactivity of total microsomal protein decreases with time with a half-time of about 3 days. In phenobarbital-treated animals, however, there is a marked stabilization of microsomal protein so that almost no radioactivity is lost over a S-day period. The reduced protein catabolism is observed both in total microsomes and in a purified microsomal protein, NADPH cytochrome c reductase. Thus, repeated administration of phenobarbital to animals evokes an increase in... 

Comparison of the model-derived DIFF with the experimentally evaluated DIFF show that protein routing can be described in terms of the amount of protein synthesized from catabolic activity that is, in general it is around 20% of the mean carbon flux of the diet. A simple explanation why dp > dw is also proposed. 

TNF (17.5) Monocyte/macrophage, lymphocyte, neutrophil, endothelium, fibroblast, keratinocyte Activation of T and B cells, natural killer cells, neutrophils, and osteoblasts. Stimulation of endothelial cells to release chemotactic proteins, NO and PGI2. Tumoricidal activity. Induces fever, sleep, hepatic acute phase protein synthesis, catabolism, ACTH release. Lead to myocardial depression, hypotension/shock, hypercoagulability, and death. Stimulates production of IL-1, IL-6, IL-8, IFN-y, and H202. Suppression of cytochrome P-450, thyroglobulin, and lipoprotein lipase. Induces complement activation, release of eicosanoids, including PAF. Procoagulant activity. 

Activity of soluble protein Nitrogen catabolism regulation Translation termination Not known Not known Not known... 

Traditionally, the duration of a toxicity study depends on the intended clinical use and disease duration. The potential immunogenicity of the human protein is a significant issue since antibody binding can partially or completely inhibit the biological activity of that protein, affect its catabolism or alter its distribution and clearance. Any multiple-dose study therefore should include evaluation of the impact of antibody formation, including their neutralizing capacity. However, antibody formation in itself should not be a reason for termination of a toxicity study, particularly if the antibodies are not neutralizing or do not alter the pharmacodynamics of the protein. 

In an earlier report (J>), the decay of healthy yam tubers during storage was shown to be a result of catabolism of its proteins by an active a-glutamyl transpeptidase. There is also some alkaline proteolytic activity in the yam tuber (6), but little information is available on individual enzymes of the purine degradative pathway and on the properties of an alkaline proteinase that may function in yams during storage. This report describes the interrelation of five enzymes of ureide metabolism in fresh and stored yams, the release of ammonia in vitro by three of the enzymes that may provide an environment for alkaline proteinase activity in vivo, and the in vitro properties of an... 

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