Turnover of proteins

Cells need a certain amount of energy for maintenance. The maintenance energy is, for instance, needed for maintaining the proton motive force which is, among other purposes, used for maintaining the ion gradients across the cell membrane. Furthermore, energy is needed for the turnover of proteins and mRNA, for repair and for movement (if mobile). 

The concepts of processing and turnover of proteins have been introduced in Chapter 10, and many details have been presented in other chapters. However, as we complete our discussion of protein synthesis, it is appropriate to discuss processing further. As... 

Since there is virtually no turnover of proteins in the lens with aging, it can be expected that aging and environmental stress factors lead to changes in protein structure and water content of the lens, and that these changes... 

The planarity of the amide linkers in the protein backbone restricts rotation around the carbon-nitrogen bond. This provides some restrictions on the number of conformers that can be adopted. The linkage joining amino acids in a polymer is quite stable, but not infinitely so, and it can be relatively easily hydrolyzed by enzymes to allow turnover of proteins within cells. This propitious combination of properties is conferred by the amide bonds linking the amino acids in the polymer polymers linked by ester, thioester, ether, or carbon-carbon bonds lack one or more these properties. 

Water, however, carries both nucleophilic and electrophilic centers. This means that water reacts with many biomolecules in a way that damages them. In the case of proteins, as noted above, water reacts with the amide backbone to degrade proteins, generating amino acids as hydrolysis products (see Figure 2.13). This can be disadvantageous if the protein is desired, as it requires that the protein be re-synthesized. The turnover of proteins is important, however, in any system living in a dynamic environment. Thus, the hydrolytic instability of proteins in water is key to maintaining life. 

Intracellular Turnover. There are many proteases involved in the turnover of proteins at the intracellular level, all of which have rather restricted specificity. These enzymes, while also present in the cytoplasm, are highly concentrated in the lysosomes. They generally are referred to as cathepsins and include both endo- and exosplitting hydrolases. 

These proteases have been studied extensively because of their importance in the continuous turnover of proteins at the cellular level. The reader is referred to several recent excellent reviews (16,17,18). In this chapter, we shall concentrate on the specificity of protein turnover as an example of the potential that exists for selective hydrolytic modifications of food proteins. 

Table IX. Factors Affecting Intracellular Turnover of Proteins ...

The major metabolic, developmental and signal responsive pathways are determined by the functionality of proteins (notably enzymes) and the amounts of particular proteins. The turnover of proteins is determined by the dichotomy of gene expression (protein synthesis) and protein degradation. The nature and regulation of these various pathways are sketched below. 

Q3 The thyroid hormones thyroxine and triiodothyronine have many metabolic effects. In adults they increase metabolic rate, oxygen and calorie consumption, stimulate carbohydrate metabolism and turnover of protein, deplete fat stores and increase catabolism of free fatty acids. Thyroid hormones stimulate heart rate and force and increase pulmonary ventilation, gastrointestinal motility and central nervous system (CNS) activity. Actions on the heart can result in an increased incidence of dysrhythmias. Thyroid hormones are critical for the normal growth and development of the infant, particularly in respect of skeletal growth and maturation of the CNS. 

One of the most thoroughly studied problems is the turnover of proteins in the bodies of animals, plants and man, in cells and subcellular structures, in the blood stream, the digestive tract and so on. Different approaches have been chosen for such studies and among them the use of labeled proteins or their labeling in vivo plays an important role (e.g. 

Mapping of protein (post-translational) modifications, which determine targeting, stracture, function, and turnover of proteins (Ch. 19). 

Metabolic activation of PAHs consists of an oxidation of the rings of unsubstituted PAHs. These oxidations are carried out by mixed function oxidases of the liver which contain cytochromes P450 and P448 and require reduced nicotine adenine dinucleotide and oxygen. In this oxidation, an epoxide intermediate is formed which has been shown to have the requisite chemical reactivity to bind covalently with DNA and histones and to serve as the ultimate carcinogenic form of PAH. Administration of 3-MC to rats increased hepatic nuclear proteins and caused a turnover of protein of the endoplasmic reticulum. Studies of " C amino acid incorporation showed that 3-MC causes increased protein synthesis and reduced degradation of protein. 

Von Hungen, K., Mahler, R. and Moore, W. J. (1968) Turnover of protein and ribonucleic acid in synaptic subcellular fractions from rat brain. J. biol. Chem., 243, 1415-1423. 

There is a constant turnover of protein nucleic acids, signifying both synthesis and degradation (Cory, in Devlin, 1986, pp. 659,660). Synthesis is in part dependent on the enzyme deoxyuridine triphosphatase (dUTPase), and the Cory reference notes that dUTPase may in fact be a factor in cancer proliferation. 

---