Endoplasmic reticulum microsomes

Monooxygenases owe their catalytic properties to the hemeprotein cytochrome P450 (Fignre 2.3). Within the membrane of the endoplasmic reticulum (microsomal... 

Initial studies designed to obtain a valid subcellular fractionation scheme for rainbow trout liver illustrated the aryl-hydrocarbon (benzo[a]pyrene] hydroxylase activity separated with glucose-6-phosphatase (35). This observation indicated that the trout hemoprotein P-450-mediated monooxygenation system was located within the endoplasmic reticulum (microsomal fraction). 

Figure 22-3. Transport and hepatic metabolism of bilirubin. Bilirubin that is produced in phagocytes is transported to liver as an albumin-bilirubin complex. Uptake into the hepatocytes takes place in liver sinusoids. Within the hepatocyte, bilirubin is transported to the endoplasmic reticulum (microsomes) bound to glutathione S-transferase (GST). Bilirubin is made water soluble by addition of one or two glucuronic acid moieties obtained from UPD-glucuronic acid, catalyzed by bilirubin-UDP-glucuronyltransferase. The product, conjugated bilirubin, is transported across the bile canalicular membrane for secretion into the biliary system, with subsequent movement into the intestines.

Microsomal epoxide hydrolase is widely distributed, having been described from plants, invertabrates, and vertebrates. In vertebrates it has wide organ distribution for example, in the rat, the most studied species, the enzyme has been found in essentially every organ and tissue. Although predominantly located in the endoplasmic reticulum (microsomes), epoxide hydrolase is also found in the plasma and nuclear membranes and, to some extent, in the cytosolic fraction. 

Transformation of lanosterol to cholesterol (Figure 19-16) is a complex, multistep process catalyzed by enzymes of the endoplasmic reticulum (microsomes). A cytosolic sterol carrier protein is also required and presumably functions as a carrier of steroid intermediates from one catalytic site to the next but may also affect activity of the enzymes. The reactions consist of removal of the three methyl groups attached to C4 and C14, migration of the double bond from the 8,9- to the 5,6-position, and saturation of the double bond in the side chain. Conversion of lanosterol to cholesterol occurs principally via 7-dehydrocholesterol and to a minor extent via desmosterol. 

Phase 1. The most important enzyme involved in biotransformation is cytochrome P-450 which catalyses many phase 1 reactions. This enzyme is located primarily in the smooth endoplasmic reticulum (microsomal fraction) of the cell and is especially abundant in liver cells. Cytochrome P-450 primarily catalyses oxidation reactions and consists of many isoforms (isozymes). These isoenzymes have overlapping substrate specificities. There are other components of the P-450 system, namely NADPH cytochrome P-450 reductase NADH cytochrome b5 reductase cytochrome b5. 

Cholesterol and many of its biosynthetic precursors are highly insoluble in aqueous media. Yet, cholesterol biosynthesis, utilization and intracellular transfers occur in environments which involve both aqueous and nonaqueous components. For example, the enzymes involved in the conversion of squalene to cholesterol, the conversion of cholesterol to cholesterol esters, and the conversion of cholesterol to 7a-hydroxycholesterol are associated with the endoplasmic reticulum (microsomes). The conversion of cholesterol to pregnenolone, an essential first step in steroid hormone biosynthesis, occurs in mitochondria. In addition, transfers of cholesterol from cytoplasmic lipid inclusion droplets through the cytosol to the mitochondria are essential for steroid hormone production. 

Rowe, T., Aridor, M., McCaffery, J. M., Plutner, H., Nuoffer, C., and Balch, W. E. (1996). COPII vesicles derived from mammalian endoplasmic reticulum microsomes recruit COPI. J. Cell. Biol 135, 895-911. 

As discussed above, in retinol deficiency newly synthesized apo-RBP accumulates in the hepatic endoplasmic reticulum (microsomal fraction), whereas the secretion of serum albumin, TTR, and other plasma proteins appears to continue at a normal rate. The mechanisms responsible for the selective retention of RBP in the endoplasmic reticulum and for the specific stimulation of RBP secretion when retinol is made available, are not known. 

Second, the use of S-9 assumes that no mitochondrial or nuclear enzymes could have a direct involvement in mutagenesis. It is only speculative at this point not to agree necessarily with this assumption. However, there is evidence that an isomer of the insecticide DDD used in the treatment of adrenal cortical carcinoma, Mitotane, is converted to covalently binding species by mitochondria, but not by microsomes or the soluble fraction isolated from canine adrenal cortex tissue. Likewise, Bresnick has postulated that the nuclear mixed-function oxidases contribute in vivo to that activation of polycyclics that leads to mutagenesis and carcinogenesis, while the enzymes in the endoplasmic reticulum (microsomes) are more involved with the detoxification of these chemicals. Bresnick et have demonstrated with histofluorescence tech-... 

The endoplasmic reticulum. Microsomes Most cells have a highly convoluted internal membrane, which forms an extensive network of tubules that seems almost to fill the cytoplasm. This membrane, called the endoplasmic reticulum (or e.r. for short), is a lipoprotein mosaic very much like the plasma membrane. 

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