Protein extracellular, degradation

Defective proteins and those with characteristically short half-lives are generally degraded in both bacterial and eukaryotic cells by selective ATP-dependent cytosolic systems. A second system in vertebrates, operating in lysosomes, recycles the amino acids of membrane proteins, extracellular proteins, and proteins with characteristically long half-lives. 

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. 

Qiu WQ, Walsh DM, Ye Z, Vekrellis K, Zhang J, Podhsny MB, Rosner MR, Safavi A, Hersh LB, Selkoe DJ (1998) Insulindegrading enzyme regulates extracellular levels of amyloid beta-protein by degradation. J Biol Chem 273 32730-32738. 

The proteinase is capable of degrading elastin, although at a much slower rate than NE, as well as numerous other protein substrates such as collagen, fibro-nectin, and laminin [34,35]. The extent to which cathepsin G participates in extracellular degradation is still unclear, however, it has been suggested that cathepsin G acts in a synergistic manner to facilitate the degradation of elastin by NE [34]. 

Cathepsins are lysosomal proteases which are designed to function in an acidic milieu. Although the specific roles of each protease are not yet defined, it seems likely that extracellular proteins taken up by a cell and long-lived cellular proteins are degraded in lysosomes, while selective protein turnover related to metabolic regulation occurs in other compartments. 

Primary mixed cultures prepared from the brains of newborn Wistar rats were able to remove added oxidized laminin and myelin basic protein from the extracellular environment (Stolzing et al. 2002). Moderately oxidized proteins were degraded most efficiently, whereas strongly oxidized proteins were taken up by the microglial cells without an efficient degradation. Stimulation of microglial cells by lipopolysaccharide from Escherichia coli (10 or 12-0-tetradecanoylphorbol-13-... 

Cathepsins are intracellular proteinases that reside within lysosomes or specific intracellular granules. Cathepsins are used to degrade proteins or pqffides that are internalised from the extracellular space. Some cathepsins such as cathepsin-G or cathepsin-K may be released from the cell to degrade specific extracellular matrix proteins. All cathepsins except cathepsin-G (serine) and cathepsin-D (aspartyl) are cysteine proteinases. 

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