Proteins - continued turnover

Connective tissue is composed of apparently very different cells metabolically it is dynamic undergoing continual turnover and so to maintain health means that a balance must be achieved between biosynthesis and degradation. Cells in connective tissue are usually found embedded within a matrix composed of proteins with variable amounts of proteoglycan and genetically determined enzymatic defects in the production of the matrix may result in often serious pathologies. Metabolism in... 

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. 

Tissue remodelling in normal healthy tissue is dependent upon continuous turnover of connective tissue elements. This requires dissolution of structural matrix proteins, and laying down of new structural components. Acute... 

Collagen is one of the most abundant and widespread proteins in the animal kingdom. It is the basic fibrous constituent of tendon, skin, cartilage, and bone, and occurs in practically every organ of the body. In its native state it is maintained in equilibrium with tissue fluids, the weight fraction of collagen being about 0.3. It is an extracellular protein and once formed is metabolically stable in most sites this is in contrast to other body proteins which show a continuous turnover of molecules. ... 

As discussed in section 9.1.1, there is continual turnover of proteins in the cell, and not all proteins are broken down and replaced at the same rate. Some are relatively stable, whereas others, and especially enzymes that are important in metabolic regulation, have short half-lives — of the order of minutes or hours. This rapid turnover means that it is possible to control metabolic pathways by changing the rate at which... 

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. 

How the division of spoils came about I do not recall—it may have been by drawing lots. At any rate, David Shemin drew amino acid metabolism, which led to his classical work on heme biosynthesis. David Rittenburg was to continue his interest in protein synthesis and turnover, and lipids were to be my territory. 

An initially surprising conclusion drawn from the studies of Schoenheimer and Rittenberg was that proteins within cells are in a continuous steady state of synthesis and degradation. The initial biosynthesis, the processing, oxidative and hydrolytic degradative reactions of peptides, and further catabolism of amino acids all combine to form a series of metabolic loops as discussed in Chapter 17 and dealt with further in Chapters 12 and 29. Within cells some proteins are degraded much more rapidly than others, an important aspect of metabolic control. This is accomplished with the aid of the ubiquitin system (Box 10-C) and proteasomes (Box 7-A).107 Proteins secreted into extracellular fluids often undergo more rapid turnover than do those that remain within cells. 

Figure 20.4 The Picou and Taylor-Roberts model for studying whole-body protein turnover. Nitrogen enters the metabolic pool via I and C, and exits via Er and S. [1 N]-glycine is infused continuously, and represents the label for overall nitrogen entry into the pool. (Reproduced with permission from Steffee WP, Goldsmith RS, Pencharz PB, Scrimshaw NS, Young VR. Dietary protein intake and dynamic aspects of whole body nitrogen metabolism in adult humans. Metabolism 25 281-297, 1976.)...

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