Membrane endoplasmic reticulum

FIGURE 23.8 Glu cose-6-phosphatase is localized in the endoplasmic reticulum membrane. Conversion of glucose-6-phosphate to glucose occurs during transport into the ER. 

This impressive reaction is catalyzed by stearoyl-CoA desaturase, a 53-kD enzyme containing a nonheme iron center. NADH and oxygen (Og) are required, as are two other proteins cytochrome 65 reductase (a 43-kD flavo-protein) and cytochrome 65 (16.7 kD). All three proteins are associated with the endoplasmic reticulum membrane. Cytochrome reductase transfers a pair of electrons from NADH through FAD to cytochrome (Figure 25.14). Oxidation of reduced cytochrome be, is coupled to reduction of nonheme Fe to Fe in the desaturase. The Fe accepts a pair of electrons (one at a time in a cycle) from cytochrome b and creates a cis double bond at the 9,10-posi-tion of the stearoyl-CoA substrate. Og is the terminal electron acceptor in this fatty acyl desaturation cycle. Note that two water molecules are made, which means that four electrons are transferred overall. Two of these come through the reaction sequence from NADH, and two come from the fatty acyl substrate that is being dehydrogenated. 

Endoplasmic reticulum Membranous network of cells that contains many enzymes that metabolize xenobiotics. Hepatic microsomes consist mainly of vesicles derived from the endoplasmic reticulum of liver. 

Most living cells, including muscle, maintain the cytoplasmic Ca concentration at submicromolar levels, against steep gradients of [Ca ], both at the cell surface and across the endoplasmic reticulum membrane [17]. In the musele cell two membrane systems are primarily involved in this function the sarcoplasmic reticulum and the surface membrane. 

The steroid ring hydroxylation proceeds with the involvement of the monooxygen-ase chain of endoplasmic reticulum membranes. 

Walter, P., andjohnson, A. E. (1994). Signal sequence recognition and protein targeting to the endoplasmic reticulum membrane. Annu. Rev. Cell Biol. 10, 87—119. 

Fehr, M., Takanaga, H., Ehrhardt, D. W. and Frommer, W. B. (2005b). Evidence for high-capacity bidirectional glucose transport across the endoplasmic reticulum membrane by genetically encoded fluorescence resonance energy transfer nanosensors. Mol. Cell. Biol. 25, 11102-12. 

Insulin was first identified as an anti-diabetic factor in 1921, and was introduced clinically the following year. Its complete amino acid sequence was determined in 1951. Although mature insulin is a dimeric structure, it is synthesized as a single polypeptide precursor, i.e. preproinsulin. This 108 amino acid polypeptide contains a 23 amino acid signal sequence at its amino terminal end. This guides it through the endoplasmic reticulum membrane, where the signal sequence is removed by a specific peptidase. 

Kuroiwa, T., Sakaguchi, M., Mihara, K., and Omura, T. (1991). Systematic analysis of stop-transfer sequence for microsomal membrane. Biol. Chem. 266, 9251—9255. Kuroiwa, T., Sakaguchi, M., Omura, T., and Mihara, K. (1996). Reinitiation of protein translocation across the endoplasmic reticulum membrane topogenesis of multispan-ning membrane proteins. J. Biol. Chem. 271, 6243—6248. 

Ng, T., Brown, J., and Walter, P. (1996). Signal sequences specify the targeting route to the endoplasmic reticulum membrane. J. Cell Biol. 134, 269-278. 

Hampton, R. Y., R. G. Gardner, and J. Rine, Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Md Biol Cell, 1996, 7(12), 2029 4. 

Mayer TU, Braun T, Jentsch, S (1998) Role of the proteasome in membrane extraction of a short-lived ER-transmembrane protein. EMBO ] 17 3251-3257 McCracken AA, Brodsky JL (1996) Assembly of ER-associated protein degradation in vitro dependence on cytosol, calnexin, and ATP. J Cell Biol 132 291-298 McDonald HB, Byers B (1997) A proteasome cap subunit required for spindle pole body duplication in yeast. J Cell Biol 137 539-553 McGee TP, Cheng HH, Kumagai H, Omura S, Simoni RD (1996) Degradation of 3-hydroxy-3-methylg utaryl-CoA reductase in endoplasmic reticulum membranes is accelerated as a result of increased susceptibility to proteolysis. J Biol Chem 271 25630-25638... 

The PAL activity that is necessary for lignin formation occurs in the cytoplasm or bound to the cytoplasmic surface of the endoplasmic reticulum membranes. The cinnamic acid produced is probably carried on the lipid surface of the membranes, since it is lipophilic, and it is sequentially hydroxylated by the membrane-bound hydroxylases (47,50). In this way there is the possibility of at least a two-step channeling route from phenylalanine to p-coumaric acid. The transmethylases then direct the methyl groups to the meta positions. There is a difference between the transmethylases from angiosperms and those from gymnosperms, since with the latter... 

Many substrates, by virtue of their relatively high lipophilicity, are not only retained at the active site of the enzyme but remain nonspecifically bound to the lipid endoplasmic reticulum membrane. In this state, they may induce microsomal enzymes, particularly after repeated use. Acutely, depending on the residual drug levels at the active site, they also may competitively inhibit metabolism of a simultaneously administered drug. 

Figure 32-4 Sketch illustrating only a few of the many aspects of apoptosis in a mammalian cell. Emphasis here is on the death receptor pathways and cytochrome c-activated apoptosis. A third pathway is initiated by stress in endoplasmic reticulum membranes. In addition, attack by cytolytic T cells sometimes causes apoptosis by action of a granzyme on protein Bid or via a death receptor. Objects in scheme are not drawn to a single scale.

The concentration of dolichyl phosphate in eukaryotic tissues is very low and is probably rate-limiting for the glycosylation processes. Variation of the concentration in the endoplasmic-reticulum membranes is a possible way of controlling the rate of glycosylation. It is important to point out that the early steps in the dolichol biosynthesis are common to such other prenyl derivatives in plants as steroids, essential oils, hormones, phytol, and carotenes (see Scheme 1), and parameters affecting those reactions that may control the dolichol to dolichyl phosphate step could be another mechanism for regulation of the level of dolichyl phosphate. 

Proposed structure of HMG-CoA reductase derived from studies of recombinant DNA that codes for the enzyme. The enzyme is attached to the endoplasmic reticulum membrane and consists of two domains the hydrophobic domain, embedded in the membrane, and the catalytic domain, which protrudes into the cytosol. (Source Adapted from L. Liscum, J. Finer-Moore, R. M. Stroud, K. L. Luskey, M. S. Brown, and J. L. Goldstein, Domain structure of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a glycoprotein of the endoplasmic reticulum, J. Biol. Chem. 260 522-530, 1985.)... 

Blobel discovered the mechanism for protein translocation across the endoplasmic reticulum membrane—the signal hypothesis. 

Hrazdina G, Zobel AM, Hoch HC. 1987. Biochemical, immunological, and immuno-cytochemical evidence for the association of chalcone synthase with endoplasmic reticulum membranes. Proc Natl Acad Sci USA 84 8966-8970. 

Glazner G.W., and Fernyhough P. 2002 Neuronal survival in the balance are endoplasmic reticulum membrane proteins the fulcrum Cell Calcium 32, 421-433. 

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