Protein turnover rate

It was just stated that protein turnover has anabolic and catabolic arms. In a subject in a steady metabolic state, these are exactly equal. It may then be of interest to determine the absolute rates of protein synthesis/degradation. Individual protein turnover rates may be expressed in terms of half-lives (tiy) or fractional catabolic rates or simply in terms of grams protein synthesized and degraded per unit time. The same parameters can be derived for whole-body protein turnover. 

Another signal for protein degradation, independent of ubiquitination, is the presence of PEST sequences, which are amino-acid sequences containing large amounts of Pro (P), Glu (E), Ser (S), and Thr (T). The presence of multiple PEST sequences is correlated with high turnover rates of proteins. Experiments have shown that, for some proteins, removal of the PEST sequences can result in protein stabilization. However, the mechanism by which PEST sequences determine protein turnover rates is still not known, although it is thought to be mediated by sequence-selective proteases. 

The concentration of amino acids in the blood of patients with liver disease is often elevated. This change is, in part, attributable to a significantly increased rate of protein turnover (general catabolic effect seen in severely ill patients) as well as to impaired amino acid uptake by the diseased liver. It is unlikely that the increased levels are due to degradation of liver protein and the subsequent release of amino acids from the failing hepatocyte into the blood. This is true because the total protein content of the liver is only approximately 300 g. To account for the elevated amino acid levels in the blood, the entire protein content of the liver would have to be degraded within 6 to 8 hours to account for the increased protein turnover rates found. Because 18 to 20 times more protein is present in skeletal muscle (greater mass), the muscle is probably the major source of the elevated plasma levels of amino acids seen in catabolic states such as cirrhosis of the liver. 

Maeda, Y., Hayashi, K., Hashiguchi, T. Okamoto, S. (1986). Genetic studies on the muscle protein turnover rate of Cotumix quail. Biochem. Genet., 24, 207-16. 

In an attempt to exclude the use of urea from protein turnover measurements, [ N]lysine has been infused intravenously until the free lysine in the plasma achieved plateau labelling [431]. From the lysine flux, and its mean representation in all body proteins, turnover rates were calculated in a manner analogous to that used in radioactive amino acid studies [432]. In addition, serial muscle biopsies taken 14—16h apart when plasma [ N] lysine plateau conditions prevailed, enabled muscle protein turnover rate to be calculated. This was found to account for 53% of whole body protein turnover. 

The strain will be screened for other possible alterations In post-expontenlal Intracellular events l.e. protein turnover rates amount of protease produced as well as possible susceptibility of sporulatlng cells to fungal proteases. 

Enzymes are excellent catalysts for two reasons great specificity and high turnover rates. With but few exceptions, all reac tions in biological systems are catalyzed by enzymes, and each enzyme usually catalyzes only one reaction. For most of the important enzymes and other proteins, the amino-acid sequences and three-dimensional structures have been determined. When the molecular struc ture of an enzyme is known, a precise molecular weight could be used to state concentration in molar units. However, the amount is usually expressed in terms of catalytic activity because some of the enzyme may be denatured or otherwise inactive. An international unit (lU) of an enzyme is defined as the amount capable of producing one micromole of its reaction product in one minute under its optimal (or some defined) reaction conditions. Specific activity, the activity per unit mass, is an index of enzyme purity. 

Our results do not support the protein stress model. However, this model may apply in cases where stress is intermittent and results in tissue loss, as observed in the study of crows (Hobson and Clark 1992). Low protein levels throughout life after weaning may have produced overall slow and reduced rate of growth rather than tissue loss. Adult rats fed protein-deficient diets after maturation show systematic losses of nitrogen from most tissues that are in proportion to their turnover rates and masses (Uezu et al. 1983). Perhaps tissue nitrogen isotope enrichment may occur under these conditions. New experiments are needed to evaluate this hypothesis. 

In this cycle, step 3, the dissociation of the two proteins, is rate determining and is rate determining in the overall enzyme turnover. 

Membranes and their components are dynamic structures. The lipids and proteins in membranes undergo turnover there just as they do in other compartments of the cell. Different lipids have different turnover rates, and the turnover rates of individual species of membrane proteins may vary widely. The membrane itself can turn over even more rapidly than any of its constituents. This is discussed in more detail in the section on endocytosis. 

It has been shown that the half-lives of the lipids of the ER membranes of rat liver are generally shorter than those of its proteins, so that the turnover rates of lipids and proteins are independent. Indeed, different lipids have been found to have different half-Eves. Furthermore, the half-lives of the proteins of these membranes vary quite widely, some exhibiting short (hours) and others long (days) half-lives. Thus, individual lipids and proteins of the ER membranes appear to be inserted into it relatively independently this is the case for many other membranes. 

After secretion from the cell, certain lysyl residues of tropoelastin are oxidatively deaminated to aldehydes by lysyl oxidase, the same enzyme involved in this process in collagen. However, the major cross-links formed in elastin are the desmosines, which result from the condensation of three of these lysine-derived aldehydes with an unmodified lysine to form a tetrafunctional cross-hnk unique to elastin. Once cross-linked in its mature, extracellular form, elastin is highly insoluble and extremely stable and has a very low turnover rate. Elastin exhibits a variety of random coil conformations that permit the protein to stretch and subsequently recoil during the performance of its physiologic functions. 

The preparation of antibodies specific for the individual plasma proteins has greatly facilitated their smdy, allowing the precipitation and isolation of pure proteins from the complex mixmre present in tissues or plasma. In addition, the use of isotopes has made possible the determination of their pathways of biosynthesis and of their turnover rates in plasma. 

After this initial phase of infection subsides, the free viral load in the blood declines, often to almost undetectable levels. This latent phase may last for anything up to 10 years or more. During this phase, however, there does seem to be continuous synthesis and destruction of viral particles. This is accompanied by a high turnover rate of (CD4+) T-helper lymphocytes. The levels of these T-lymphocytes decline with time, as does antibody levels specific for viral proteins. The circulating viral load often increases as a result, and the depletion of T-helper cells compromises general immune function. As the immune system fails, classical symptoms of AIDS-related complex (ARC) and, finally, full-blown AIDS begin to develop. 

Myelin components exhibit great heterogeneity of metabolic turnover. One of the novel characteristics of myelin demonstrated in early biochemical studies was that its overall rate of metabolic turnover is substantially slower than that of other neural membranes [1]. A standard type of experiment was to evaluate lipid or protein turnover by injecting rat brains with a radioactive metabolic precursor and then follow loss of radioactivity from individual components as a function of time. Structural lipid components of myelin, notably cholesterol, cerebro-side and sulfatide, as well as proteins of compact myelin, are relatively stable, with half-lives of the order of many months. One complication in interpreting these studies is that the metabolic turnover of individual myelin components is multiphasic - consisting of an initial rapid loss of radioactivity followed by a much longer slower loss. 

In addition to more rapid absorption of lipids in animals fed casein, another mechanism that may be operative is decreased clearance of circulating lipids. Rabbits fed a casein-based semipurified diet excreted significantly less cholesterol but more bile acids in their feces than animals fed a commercial diet (18). The total sterol excretion in feces of the animals fed the casein diet was half that of the rabbits fed the stock diet. Huff and Carroll (19) found that rabbits fed soy protein had a much faster turnover rate of cholesterol and a significantly reduced rapidly exchangeable cholesterol pool compared with rabbits fed casein. Similar studies performed in our laboratory revealed that the mean transit time for cholesterol was 18.4 days in rabbits fed soy protein, 36.8 days in rabbits fed casein, 33.7 days in rabbits fed soy plus lysine, and 36.3 days in rabbits fed casein plus arginine. These data suggest that addition of lysine to soy protein... 

There are at least two factors that could influence the turnover rate, the site of metabolism (hot spot) and the affinity of a compound toward these enzymes the protein/ligand (substrate or inhibitor) interaction and the chemical reactivity of the compound towards oxidation. Because of the interaction of the protein with the potential ligand, certain atoms of the compound could be exposed to the heme group, and depending on the chemical nature of these moieties the oxidative reaction will take place at different rates, for example celecoxib is metabolized by CYP2C9 at the... 

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