Cholesterol storage

Cholesterol storage in lysosomes/endosomes is a hallmark of Niemann-Pick type C disease. The assay is based on the procedure described by Vanier et al. [58]. 

HMG-CoA reductase, a rate-limiting enzyme of cholesterol synthesis, and ACAT-1, a rate-limiting enzyme of cholesterol esterification, relate to hepatic cholesterol storage. Levels of mRNA of those enzymes were also increased by the lipodystrophy model diet during the onset of hepatic steatosis, but DHA supplementation attenuated this (Fig. 22.6). 

Elevation of cholesterol is found in fatty liver, particularly under diabetic metabolic conditions. A rather marked increase in cholesterol can be observed in all forms of cholestasis differentiation between intra- or extrahepatic cholestasis, however, is not possible. This elevation of cholesterol in obstruction is due to an enhanced synthesis of cholesterol in hepatocytes and intestinal walls as well as to the retention of bile lipids. Marked elevations of cholesterol are detectable in primary biliary cirrhosis and in cholesterol storage disease. A pronounced increase in cholesterol is also found in Zieve s syndrome (L. Zieve, 1958). 

Niemann-Pick disease type C—A cholesterol storage disease... 

HMGCoA reductase step, which can be inhibited either by cholesterol or phosphorylation of the enzyme, as mediated indirectly by increases in intracellular cAMP. With severe hypercholesterolemia, people may be treated with an HMGCoA reductase inhibitor, such as lovastatin. Cholesterol storage and delivery is controlled by a number of LDL receptors. Low-density lipoprotein is a cholesterol-rich lipoprotein which can deliver cholesterol to many tissues via LDL receptors. As tissue cholesterol levels rise, the importance of cholesterol delivery is less important. When cellular cholesterol levels are high, there is a down-regulation of LDL receptors (a decrease in the number of receptors),... 

These findings explain the increased body cholesterol storage in obesity but what of the accelerated cholesterol synthesis To answer this question we obtained adipose tissue from obese patients and measured the incorporation of radioactive glucose into cholesterol. The results showed very little cholesterol synthesis under a wide variety of conditions. These included addition of insulin to the medium, and varying the diets or reducing the patients weights. 

The quaHty, ie, level of impurities, of the fats and oils used in the manufacture of soap is important in the production of commercial products. Fats and oils are isolated from various animal and vegetable sources and contain different intrinsic impurities. These impurities may include hydrolysis products of the triglyceride, eg, fatty acid and mono/diglycerides proteinaceous materials and particulate dirt, eg, bone meal and various vitamins, pigments, phosphatides, and sterols, ie, cholesterol and tocopherol as weU as less descript odor and color bodies. These impurities affect the physical properties such as odor and color of the fats and oils and can cause additional degradation of the fats and oils upon storage. For commercial soaps, it is desirable to keep these impurities at the absolute minimum for both storage stabiHty and finished product quaHty considerations. 

One limitation of enzyme replacement therapy is the targeting of enzyme proteins to appropriate sites of substrate accumulation. Administration of a cholesterol esterase conjugated to albumin results in the degradation of pathologic cholesterol ester accumulations within the lysosomes of fibroblasts from a patient with cholesterol ester storage disease (246). 

CYP27A1 catalyzes the side chain oxidation (27-hydroxylation) in bile acid biosynthesis. Because bile acid synthesis is the only elimination pathway for cholesterol, mutations in the CYP27A1 gene lead to abnormal deposition of cholesterol and cholestanol in various tissues. This sterol storage disorder is known as cerebrotendinous xanthomatosis. CYP27B1 is the 1-alpha hydroxylase of vitamin D3 that converts it to the active vitamin form. The function of CYP27C1 is not yet known. 

Fat absorbed from the diet and lipids synthesized by the liver and adipose tissue must be transported between the various tissues and organs for utilization and storage. Since lipids are insoluble in water, the problem of how to transport them in the aqueous blood plasma is solved by associating nonpolar lipids (triacylglycerol and cholesteryl esters) with amphipathic hpids (phospholipids and cholesterol) and proteins to make water-miscible hpoproteins. 

Cholesterol, a polycyclic alcohol [Fig. 3(1)] is present in all animal tissues. It is a major constituent of cellular membranes, where it contributes to the fluidity of the membrane. The storage and transport forms of cholesterol are its esters with fatty acids. 

Lipids Fats and oils Energy storage (reserve fuel) Vegetable oils, animal fats, cholesterol, hormones 1-30... 

Wolman s disease Cholesterol ester storage disease Acid lipase Cholesterol ester... 

Probucol (4,4/-[(l-methylethylidene)bis(thio)]-bis-[2,6-bis(l,l-dime-thylethyl)phenol]) is a cholesterol-lowering drug that has been reported to exist in two forms [27]. Form II has been found to exhibit a lower melting point onset relative to Form I, and samples of Form II spontaneously transform to Form I upon long-term storage. The structures of these two polymorphic forms have been reported, and a summary of the crystallographic data obtained in this work is provided in... 

K38. Kronenberg, F., Lobenstanz, E.-M., Konig, P., Utermann, G., and Dieplinger, H., Effect of sample storage on the measurement of lipoprotein(a), apolipoproteins B and A-IV, total and high density lipoprotein cholesterol and triglycerides. J. Lipid Res. 35, 1318-11328 (1994). 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

Phospholipid concentration was determined using our modification of Bartlett s procedure (49,53). Cholesterol concentration and purity were determined by HPLC or enzymatically by cholesterol oxidase (49,53). Purity of phospholipids as raw materials, and the extent of their hydrolysis during various steps of liposome preparation and liposome storage, were assessed by TLC and enzymatic determination of the increase in level of nonesterified fatty acids (10,38,49-51,53). 

In capillaries of adipose tissue (and muscle), apoC-II activates lipoprotein lipase, the fetty adds released enter the tissue for storage, and the glycerol is retrieved by the liver, which has glycerol kinase. The chylomicron remnant is picked up by hepatocytes through the apoE receptor thus, dietary cholesterol, as well as any remaining triglyceride, is released in the hepatocyte. 

---