Depolymerization of protein

Other phenomena of interest here are the radiation-induced polymerizations and depolymerization of protein chains. These reactions are quite analogous to those reported for other polymers (Sec. IIIB3). 

Water is not just the solvent in which the chemical reactions of living cells occur it is very often a direct participant in those reactions. The formation of ATP from ADP and inorganic phosphate is an example of a condensation reaction in which the elements of water are eliminated (Fig. 2-22a). The reverse of this reaction— cleavage accompanied by the addition of the elements of water—is a hydrolysis reaction. Hydrolysis reactions are also responsible for the enzymatic depolymerization of proteins, carbohydrates, and nucleic acids. Hydrolysis reactions, catalyzed by enzymes called... 

The membrane tubules and lamellae of the endoplasmic reticulum (ER) are extended in the cell with the use of MTs and actin filaments. Kinesin motors are required for stretching out the ER, whereas depolymerization of microtubules causes the retraction of the ER to the cell centre in an actin-dependent manner. Newly synthesized proteins in the ER are moved by dynein motors along MTs to the Golgi complex (GC), where they are modified and packaged. The resulting vesicles move along the MTs to the cell periphery transported by kinesin motors. MTs determine the shape and the position also of the GC. Their depolymerization causes the fragmentation and dispersal of the GC. Dynein motors are required to rebuild the GC. 

The ER has a reticular morphology which provides a large surface area, which presumably is required for the synthesis and transport of proteins and lipids and for the storage of calcium. The ER is associated with microtubules, and the two are highly interdependent structures. Terasaki et al. (1986) found that when microtubules in the cell are depolymerized by colchicine, the ER network slowly retracts toward the center of the cell. If the microtubules are repolymerized, the ER network is restored to its original morphology, thereby suggesting that the MTs participate in the formation and maintenance of the ER. 

The partially methylated monosaccharides obtained on depolymerization of the permethylated sample are preferably analyzed as acetates by g.l.c.-m.s., as shown by Bjomdal and coworkers.41,42 The neutral sugars and the amino sugars obtained in acetolysis-acid hydrolysis are reduced, and acetylated for the analysis, and the amino-hexitol and the neuraminic acid residues are acetylated after methanolysis. Identification with the aid of g.l.c.-m.s. has been described for all of the common components of protein- and lipid-linked glycans and oligosaccharides from animal cells, namely, the neutral sugars,41-43 hexitols,44 hexosamines,29,43,45,46 aminohexitols,31,32 and neuraminic acids.33,34,47... 

Summary of Proposed Models for Microtubule Assembly from Depolymerized Microtubule Protein... 

The cause of the cell cycle specificity of the bisindole alkaloids may be associated with the ability of these compounds to interact with the protein tubulin and thereby inhibit the polymerization (and depolymerization) of microtubules (16,17). In this respect the cellular pharmacology of vinca alkaloids is similar to that of other cytotoxic natural products such as colchicine or podophyllotoxin. On closer inspection, however, Wilson determined that the specific binding site on tubulin occupied by vinblastine or vincristine is chemically distinct from the site occupied by the other natural products (18). Subsequent experiments have determined that the maytansinoids, a class of ansa-macrocycles structurally distinct from the bisindoles, may bind to tubulin at an adjacent (or overlapping) site (19). A partial correlation of the antimitotic activity of these compounds with their tubulin binding properties has been made, but discrepancies in cellular uptake probably preclude any quantitative relationship of these effects (20). 

Fig. 8. Mechanism proposed for the transfer of iron from low molecular weight chelates to apotransferrin involving the intermediate ternary complex of protein-iron-chelate. The polynuclear iron must be depolymerized prior to its binding by the protein. The presence of excess chelating agents, particularly citrate, leads to the formation of the bis complex which reacts rapidly...

The best known drugs acting as antimitotics are the vinca alkaloids, vincristine (7.90) and vinblastine (7.91). They are very complex indole derivatives that nevertheless have been synthesized. Both are quite effective in various leukemias and in Hodgkin s lymphoma, but show considerable neurotoxicity. Vinblastine and vincristine bind specifically to the microtubular protein tubulin in dimeric form, precipitating depolymerization of the microtubules and functionally acting as a mitotic poison. Vinorelbine (7.92) is a semisynthetic vinca alkaloid functionally identical to vinblastine. 

Polymerization and depolymerization of actin, the main component of microfilaments, is controlled by a series of proteins, the activity of which is controlled by Ca and/or Ptdlns(4,5)P2. The Ca regulated proteins (see 6.7) are chiefly involved in processes of depolymerization of actin. Many of the proteins involved in the opposite process, actin polymerization, have specific binding sites for PtdIns(4,5)P2 and Ptlns(4)P and are regulated by the availability of phosphoinositides. Examples of such proteins are profilin, gelsolin, villin and talin (review Janmey, 1994). 

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