Endoplasmatic reticulum

The UPS also plays a major role in protein quality control. In a process known as endoplasmic associated degradation (ERAD), misfolded proteins, which are formed in the endoplasmatic reticulum, are translocated back to the cytoplasm and degraded by the proteasome. 

Vitamin K carboxylase is a transmembraneous protein in the lipid bilayer of the endoplasmatic reticulum (ER). It is highly glycosilated and its C-terminal is on the luminal side of the membrane. Besides its function as carboxylase it takes part as an epoxidase in the vitamin K cycle (Fig. 1). For the binding of the y-carboxylase the vitamin K-dependent proteins have highly conserved special recognition sites. Most vitamin K-dependent proteins are carboxy-lated in the liver and in osteoblasts, but also other tissues might be involved, e.g., muscles. 

Arf Vesicular transport between endoplasmatic reticulum and cis-Golgi apparatus... 

The site of assembly of the Lp(a) particle, by covalent linkage of apo-B100 to apo(a), is not definitively established. White et al. (W12) proved in baboon hepatocytes that inside the cell two types of apo(a) existed, of which only the larger form was recovered from the culture medium. The lower-molecular-weight form proved to be a precursor with a prolonged residence time in the endoplasmatic reticulum. Density gradient ultracentrifugation and immunoblot analysis showed that the majority of apo(a) was secreted into the medium in a... 

Today s mitochondria lack most of the genes involved in phosphohpid metabolism. Therefore, mitochondria have to import most of their hpids. Phospholipids such as phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, and phosphatidylinositol must be synthesized in the endoplasmatic reticulum under the control of nuclear genes and then transferred to mitochondria (Voelker, 2000) (Figure 1). Mitochondria use both nuclear and mitochondrial encoded proteins to further diversify phospholipids (Dowhan, 1997 Kent, 1995 Daum, 1985). Thus, a nuclear phosphatidylserine decarboxylase converts phosphatidylserine into phosphatidylethanolamine, or mitochondrial encoded cardiolipin synthase converts phosphatidylglycerol into cardiolipin which is incorporated exclusively into the inner mitochondrial membrane. 

Figure 1. Control of mitochondrial biogenesis by the nuclear genome. Most mitochondrial proteins, including cytochrome c, are nuclear gene products which are subsequently imported into mitochondria. Similarly, most enzymes involved in synthesis of mitochondrial phosphoplipids are encoded in the nuclear genome. Being located in the endoplasmatic reticulum, they synthesize phosphatidylcholine (PtdCho), phosphatidylserine (PtdSer), phosphatidylglycerol (PG) and phosphatidylinositol (Ptdins). The phospholipids are transferred to the outer membrane. The imported lipids then move into the inner membrane at contact sites. Mitochondria then diversify phospholipids. They decarboxylate phosphatidylserine to phosphatidylethanolamine (PtdEtN), but the main reaction is the conversion of imported phosphatidylglycerol to cardiolipin (CL). Cardiolipins localize mainly in the outer leaflet of the inner membrane.

K. Karaveg, A. Siriwardena, W. Tempel, Z.-J. Liu, J. Glushka, B.-C. Wang, and K. W. Moremen, Mechanism of class 1 (glycosylhydrolase family 47) a-mannosidases involved in iV-glycan processing and endoplasmatic reticulum quality control,./. Biol. Chem., 280 (2005) 16197-16207. 

Y. D. Lobsanov, F. Vallee, A. Imberty, T. Yoshida, P. Yip, A. Herscovics, and P. L. Howell, Structure of Penicillium citrinum al,2-mannosidase reveals the basis for differences in specificity of the endoplasmatic reticulum and golgi class I enzymes, J. Biol. Chem., 277 (2002) 5620-5630. 

PC2 may also function as an intracellular Ca2+ channel itself. A large population of PC2 channels can be detected in the endoplasmatic reticulum (Vassilev, Guo et al. 2001 Koulen, Cai et al. 2002 Giamarchi, Padilla et al. 2006). Until recently, it was thought there were only two major classes of intracellular Ca2+ channels the RyRs and the InsP3Rs. It is now agreed that there are three classes of intracellular channels. Many cell types contain all three classes of channels, but the relative densities vary dramatically. Cells also can have multiple isoforms of these channels. The co-existence of a variety of intracellular channels is not surprising as cells need to respond to diverse stimuli with specific responses. Whether the intracellular function of PC2 channels is relevant for the disease mechanism of PKD remains to be established. 

Fig. 3.4 Intracellular sorting by caveolae.CV caveosome ER endoplasmatic reticulum GC Golgi complex...

Cytochrome P450s are present in the endoplasmatic reticulum and therefore present in microsomal preparations. An overview on isoforms, polymorphisms, substrates, inhibitors, inducers and occurrence of cytochrome P450s is given in Table 2. 

In order to cover glucuronidation reactions in incubations in microsomal fractions several modifications have been applied in order to optimize conditions. These comprise longer incubation times than necessary for oxidative reactions by cytochrome P450s, and use of modifiers, both to overcome the latency in activity due to the diffusional barriers of the endoplasmatic reticulum (Coughtrie and Fisher 2003 Csala et al. 2004). Modifiers used are detergents or the pore-forming peptide alamethicin (Fisher 2000). Also disruption of cells by sonication is applied (Ethell 1998). 

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