Processing, Secretion, and Turnover of Proteins

The control could be established if at any one time there was at the membrane more vesicles than those that were fusing. However in order to sustain the increase in secretion it would be necessary to transmit the signal back to the synthetic system and packaging process at the Golgi apparatus so that a new steady state system was obtained. This would produce the requisite number of vesicles containing the polysaccharides necessary to maintain the new rate of fusion and secretion. The turnover of the Golgi apparatus can be very fast in plant cells and times of 5-40 minutes have been calculated (36). In vitro experiments which involved isolation of membrane fractions from maize-root cells also showed that Ca was necessary for membrane fusion (37). Analysis of the membranes indicated that the Ca dependence involved membrane proteins and one of these was a Ca and Mg -dependent ATPase (38). 

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. 

The cholesterylesters present on plasma lipoproteins are partly secreted into the plasma on nascent hpoproteins (chylomicrons and VLDL) and partly synthesized by the plasma enzyme LCAT. In some species, including man, active lipid transfer proteins (LTP) circulate in plasma. Both LCAT and LTP are synthesized in the liver (for reviews, see [25, 26]). Cholesterylester transfer protein (CETP) catalyses a transfer/exchange of cholesterylesters between HDL and the other lipoproteins. This process is important for the turnover of plasma cholesterol because, depending on the amount of active CETP and the chemical composition of the circulating plasma hpoproteins, a variable part of the HDL-cholesterylesters are transferred by CETP to hpoprotein classes of lower density, or vice versa. The presence of active CETP seems to provide a link between VLDL/IDL/LDL metabolism on one hand, and HDL metabohsm on the other. In addition LTP may directly influence the hepatic uptake of cholesterylesters from lipoproteins by as yet unknown mechanisms. 

A model depicting turnover and biosynthesis of the H,K ATPase is shown in the figure. The two subunits of the ATPase are synthesized and coassembled in the endoplasmic reticulum and proceed to the trans-Golgi. From there, tubules are budded off. The turnover of the protein in the cytoplasmic tubules is relatively slow compared to when the protein is present in the membrane of the secretory canaliculus, where it is subject to endocytosis. On the right is shown the synthesis of the two subunits followed by processing in the Golgi. The mature pump subunits are inserted into the tubulovesicles. Stimulation of add secretion by histamine or acetylcholine results in rapid movement to the secretory canaliculus (t 2 = 5 minutes). Return from the canaliculus to the tubulovesicles has a t 2 of 60 minutes. The half-life of the pump protein is approximately 50 hours. 

Part of this basal energy requirement is obvious — the heart beats to circulate the blood respiration continues and there is considerable electrical activity in nerves and muscles, whether they are working or not. These processes require a metabolic energy source. Less obviously, there is also a requirement for energy for the wide variety of biochemical reactions occurring all the time in the body laying down reserves of fat and carbohydrate (section 5.6) turnover of tissue proteins (section 9.2.3.3) transport of substrates into, and products out of, cells (section 3.2.2) and the production and secretion of hormones and neurotransmitters. 

After secretion from the cell, certain lysyl residues of tropoelastin are oxidatively deaminated to aldehydes by lysyl oxidase, the same enzyme involved in this process in collagen. However, the major cross-links formed in elastin are the desmosines, which result from the condensation of three of these lysine-derived aldehydes with an unmodified lysine to form a tetrafunctional cross-hnk unique to elastin. Once cross-linked in its mature, extracellular form, elastin is highly insoluble and extremely stable and has a very low turnover rate. Elastin exhibits a variety of random coil conformations that permit the protein to stretch and subsequently recoil during the performance of its physiologic functions. 

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