Degradation proteins

Once modified, do proteins always have the correct three-dimensional structure  

A highly important question concerns the proper folding of the newly synthesized protein. In principle, the primary structure of the protein conveys enough information to specify its three-dimensional structure. In the cell, the complexity of the process and the number of possible conformations make it less likely that a protein would spontaneously fold into the correct conformation. The Biochemical Connections box on page 356 describes the processes involved in protein folding in vivo. 

Proteins are usually modified after their initial translation. 

Protein modification includes removal of the A -formylmethionine from prokaryotic proteins, cleavage of specific amino acids, and addition of signal sequences. 

Nonprotein components can be added to some proteins, such as the heme group added to hemoglobin. 

The second stage of protein degradation is the transport of di-, tri-, and oligo-peptides into the cell. Three oligo-, di-, and tri-peptide transport systems (Opp, Dpp andDtpT, respectively) have been described in LAB. Lact. acidophilus, Lactobacillus brevis, Lact. casei, Lactobacillus rhamnosus, and L. lactis, possess all three of these peptide transport systems. Some Lact. helveticus strains, such as DPC4571, also have three peptide transport systems, while others, such as HIO, only have two (Opp and DtpT). These results indicate that the proteolytic systems differ between different strains of even the same species. Finally, Lact. reuteri only has one functional peptide transport system (DtpT) (Liu et al. 2010). 

A more dramatic difference is seen with ornithine decarboxylase (EC 4.1.1.17). This enzyme catcJyses the rale-limiting step in polyamine synthesis, and its activity in many tissues and organisms correlates well with the rate of DNA synthesis and cell proliferation. Its turnover is one of the most rapid of all enzymes, generally having a half-life of less than 20 min. Bullfield et al. (1988) have found a 20-fold higher activity in the skeletal muscle from the broiler strain compared with that in a layer strain of domestic fowl at one week of age. TTiis increased activity is almost certainly achieved by an increase in fcs with little change in fca- 

Erythrocytes are unusual compared with other tissues in that there is little turnover during the lifetime of the cell, and the proteins become degraded when the cell itself is degraded. In humans, erythrocytes have an average life of 120 days, whereas avian erythrocytes have an average life of 35 days. The principal protein in erythrocytes is haemoglobin. 

1 Short-lived proteins and energy-dependent degradation 

Much effort has been spent trying unravel the mechanism by which short-lived proteins are selected for degradation by an ATP-dependent mechanism. 

The process often involves modification by the protein ubiquitin. In skeletal muscle from the domestic fowl, which is the avian tissue most studied to date, there are a number of different pathways of proteolysis. These include lysosomal and non-lysosomal routes, some of which require ATP and ubiquitin (Fagan et al, 1992). Ubiquitin is a widely occurring protein in eukaryotes, and it becomes covalently attached to amino groups on proteins, which are then selected for degradation. The detailed steps involved in ubiquitin conjugation have been worked out in rabbit reticulocytes (Fig. 5.4). 

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A base, formed by the bacterial degradation of histidine, and present in ergot and in many animal tissues, where it is liberated in response to injury and to antigen-antibody reactions. If injected it causes a condition of shock with dilatation of many blood vessels, loss of plasma from the capillaries to the tissues and a rapid fall in blood pressure. It is normally prepared from protein degradation products. 

Mechanism of Action. P-Agonists stimulate skeletal muscle growth by accelerating rates of fiber hypertrophy and protein synthesis, but generally do not alter muscle DNA content in parallel with the increases in protein accretion (133—135). This is in contrast to the effects of anaboHc steroids and ST on skeletal muscle growth. Both of the latter stimulate fiber hypertrophy and muscle protein synthesis, but also increase muscle DNA content coincident with increased protein accretion. Whether the P-agonists decrease muscle protein degradation is equivocal. 

Supercritical Fluid Extraction. Supercritical fluid (SCF) extraction is a process in which elevated pressure and temperature conditions are used to make a substance exceed a critical point. Once above this critical point, the gas (CO2 is commonly used) exhibits unique solvating properties. The advantages of SCF extraction in foods are that there is no solvent residue in the extracted products, the process can be performed at low temperature, oxygen is excluded, and there is minimal protein degradation (49). One area in which SCF extraction of Hpids from meats maybe appHed is in the production of low fat dried meat ingredients for further processed items. Its apphcation in fresh meat is less successful because the fresh meat contains relatively high levels of moisture (50). 

Oligosaccharide Cleavage as a Timing Device for Protein Degradation... 

Mammals, fungi, and higher plants produce a family of proteolytic enzymes known as aspartic proteases. These enzymes are active at acidic (or sometimes neutral) pH, and each possesses two aspartic acid residues at the active site. Aspartic proteases carry out a variety of functions (Table 16.3), including digestion pepsin and ehymosin), lysosomal protein degradation eathepsin D and E), and regulation of blood pressure renin is an aspartic protease involved in the production of an otensin, a hormone that stimulates smooth muscle contraction and reduces excretion of salts and fluid). The aspartic proteases display a variety of substrate specificities, but normally they are most active in the cleavage of peptide bonds between two hydrophobic amino acid residues. The preferred substrates of pepsin, for example, contain aromatic residues on both sides of the peptide bond to be cleaved. 

In addition to protein proteolysis during mitosis, ubiquitin-mediated protein degradation ( ubiquitin/ proteasome) is also required at the G1 to S transition... 

Ubiquitin tags proteins for protein degradation. The ubiquitination requires three different enzymatic activities, a ubiquitin-activating enzyme (El), a ubiquitin-conjugating enzyme (E2 or Ubc) and a ubiquitin ligase (E3). The action of all three enzymes leads to the establishment of a poly-ubiquitin chain on target proteins which are then recognized and proteolyzed by the 26S proteasome. 

Hershko, A. (1988). Ubiquitin-mediated protein degradation. J. Biol. Chem. 263, 15237-15240. 

The property of thermal, reversible gelation is obtained by the addition of water-soluble proteins and protein degradation products to an aqueous solution of poly (vinyl alcohol) 2). Protein products such as albumin, gelatin, glue, a-amino acids, and their condensation products—diketopiperazines—may be used. A typical formulation for the preparation of a thermally reversible gel is ... 

Wolff, S.P., Garner, A. and Dean, RT. (1986). Free radicals, lipids and protein degradation. Trends Biochem. Sci. 11, 27-31. 

T. J. Ahern and M. J. Manning, Stability of Protein Pharmaceuticals, Part A, Chemical and Physical Pathways of Protein Degradation, Plenum Press, New York, 1992. 

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