Synthesize cholesterol

Bark beetles primarily utilize isoprenoid derived pheromones [100,101] and have been the most studied regarding their biosynthesis [8,98]. Earlier work indicated that the isoprenoid pheromones could be produced by the beetle altering host derived isoprenoids however more recent work indicates that for the most part bark beetles are producing pheromones de novo. The production of isoprenoids follows a pathway outlined in Fig. 4 which is similar to the isoprenoid pathway as it occurs in cholesterol synthesis in mammals. Insects cannot synthesize cholesterol but can synthesize farnesyl pyrophosphate. Insects apparently do not have the ability to cyclize the longer chain isoprenoid compounds into steroids. The key enzymes in the early steps of the isoprenoid... 

Although apoE HDL particles are formed by astrocytes in vitro, the brain contents of apoE knockout (-/-) were not found to differ in lipid content in comparison to those obtained from normal animals [14]. A probable explanation is that newly synthesized cholesterol can be transported from astrocyte ER to plasma membrane via an alternative route that employs caveolae to form apoAl-HDL [15]. 

Several tissues of the body are able to synthesize cholesterol de novo (i.e. from its raw materials) the liver is one of these organs. Structurally, cholesterol belongs to the group of compounds called sterols (steroid alcohols) and is derived metabolically from acetate... 

It is SREBPs which coordinate the expression of HMG CoA reductase and cell surface receptors for LDL. Cholesterol is an essential component of membranes so if delivery of cholesterol to the cell is limited by low concentrations of LDL-cholesterol, the expression of the genes for both the LDL receptor and HMG CoA reductase are up-regulated allowing the cell to extract as much as possible form the circulation and also to synthesize cholesterol, thus there is an inverse relationship between plasma LDL-cholesterol concentration and HMG CoA reductase activity. 

Like other organs, the liver also synthesizes cholesterol, which is transported to other tissues as a component of lipoproteins. Excess cholesterol is converted into bile acids in the liver or directly excreted with the bile (see p. 314). 

C]acetyl-CoA is added to a rat liver homogenate that is synthesizing cholesterol, where will the 14C label appear in A3-isopentenyl pyrophosphate, the activated form of an isoprene unit ... 

Because your body uses saturated fats to synthesize cholesterol, the more saturated fats you ingest, the more cholesterol your body is able to synthesize. Unsaturated fats, by contrast, are not ideal starting materials for cholesterol synthesis. 

Was this your answer Unsaturated fats are not so readily used by your body to synthesize cholesterol. They also tend to increase the proportion of high-density lipoproteins, which lower the level of cholesterol in your blood and help relieve the buildup of arterial plaque. 

Stereospecific 2,3-epoxidation of squalene. followed by a non-concerted carbocationic cyclization and a seiies of carbocationic rearrangements, forms lanosterol (26) in the first steps dedicated solely toward steroid synthesis. Cholesterol is the principal starting material for steroid hormone biosynthesis ill animals. The cholesterol biosynthetic pathway is composed of at least 30 enzymatic reactions. Lanosterol and squalene appear to he normal constituents, in trace amounis. in tissues that are actively synthesizing cholesterol,... 

The two significant sources of cholesterol in body are endogenously synthesized cholesterol and exogenous or dietary cholesterol. Efforts to inhibit the absorption of dietary cholesterol have primarily focused on the inhibition of ACAT, a major enzyme associated with cholesterol esterification. Inhibition of this enzyme blocks the absorption of intestinal cholesterol and may also inhibit cholesteryl ester deposition in the vascular wall in the form of fatty streaks associated with atherosclerotic plaque. 

Toxicants may selectively target glial cells for a number of reasons. Myelinating glial cells constantly synthesize cholesterol and cerebroside for myelin production thus toxicants that affect these synthetic pathways will preferentially affect myelination. The hydrophobic nature of myelin may serve as a reservoir for lipophilic toxicants... 

The adrenal gland, which is located at the cap of the kidney, is divided histologically into three zones the outer zone or zona glomerulosa, the middle zone or zona fasciculata, and the inner zone or zona reticularis. The adrenal cortex synthesizes cholesterol and pregnenolone through the interaction of a group of enzymatic reactions (Figure 61.1). 

Cholesterol is a vital component of the human body. It stabilizes cell membranes and is the precursor of bile acids, vitamin D, and steroid hormones. The body s cells can synthesize cholesterol when needed, but excess cholesterol cannot be broken down and must be excreted from the body through the bile into the small intestine. When imbalances occur, cholesterol can accumulate in the gallbladder promoting gallstone formation. Cholesterol accumulation in the bloodstream (hypercholesterolemia) can cause atherosclerotic plaques to form within artery walls. 

Cholesterol is an essential component of cellular membranes. In addition to dietary sources, we can also synthesize cholesterol. Cholesterol is transported in the blood as a lipoprotein, which is an aggregate of water-soluble proteins, cholesterol, and other lipids, including triglycerides. Proteins are denser than lipids,... 

The first stage in the synthesis of cholesterol is the formation of isopentenyl pyrophosphate Fig. 1). Acetyl CoA and acetoacetyl CoA combine to form 3-hydroxy-3-methylglutaryl CoA (HMG CoA). This process takes place in the liver, where the HMG CoA in the mitochondria is used to form ketone bodies during starvation (see Topic K2), whereas that in the cytosol is used to synthesize cholesterol in the fed state (under the influence of cholesterol). HMG CoA is then reduced to mevalonate by HMG CoA reductase Fig. 1). This is the committed step in cholesterol biosynthesis and is a key control point. Mevalonate is converted into 3-isopentenyl pyrophosphate by three consecutive reactions each involving ATP, with C02 being released in the last reaction Fig. 1). 

Cells need cholesterol to survive. Cells can either synthesize cholesterol de novo or obtain it from exogenous sources, such as lipoproteins present in the circulation (see Table 14-1 and Rader and Hobbs, 2005, for review). All of the lipoprotein classes contain phospholipids, es-terified and unesterified cholesterol, and triglycerides to varying degrees. LDL are the most abundant lipoproteins in humans. They are... 

Profiling of plasma lipoproteins and serum lipids can often aid in the diagnosis of Tangier disease. There are four classes of lipoproteins (1) chylomicrons, which transport dietary cholesterol and triglycerides from the intestines to the tissues (2) very low-density lipoproteins (VLDL) and (3) low-density lipoproteins (LDL), both of which transport de novo synthesized cholesterol and triglyceride from the liver to the tissues and (4) high-density lipoproteins (HDL), which mediate reverse cholesterol transport, a process in which excess cholesterol from peripheral tissues is transported to the liver. 

ABCA1 mediates the first step in the energy-dependent efflux of cholesterol from the cell to form HDL for reverse cholesterol transport (Fig. 15-2). While all tissues in the body can synthesize cholesterol, only the liver and steroidogenic tissues can metabolize it. Surplus cholesterol in cells of the peripheral tissues is transported to the liver for either redistribution to other cells or for excretion either as free cholesterol or as a bile salt after conversion in the liver. Therefore, this reverse cholesterol transport system plays a pivotal role in cholesterol homeostasis with HDL as one of the key players. 

Mevalonic acid, radioactively labeled at the a-carbon atom, was fed to an organism that synthesizes cholesterol. Which atoms in the cholesterol will be labeled ... 

Chemists who synthesized cholesterol benzoate about 100 years ago, a routine synthesis of a derivative of a known compound, had no way of knowing that they had opened a route to the creation of innumerable and various devices in which liquid crystals are used. This new state of a material was unexpectedly discovered in the course of studies which were narrowly focused at the preparation of various derivatives from the readily available natural compound cholesterol. Similarly, the epoch of modern chemotherapy originated with the discovery of sulfa drugs , which happened as an absolutely unexpected consequence in a broad investigation aimed at the synthesis of hundreds of most diversified derivatives of aromatic compounds, potentially useful as components of azo dyes. 

Although essentially all cells have the capacity to synthesize cholesterol from acetyl-CoA, almost 90% of synthesis... 

Once synthesized, cholesterol is released into the circulation in the form of lipoprotein, primarily very low-density lipoprotein (VLDL see later section on lipoprotein metab-... 

As IDL loses apo E and is converted to LDL with apo B-IOO as its sole apoprotein, the residence of LDL in plasma increases from several hours to 2.5 days. This long-lived, cholesterol-rich LDL serves as a source of cholesterol for most tissues of the body although most cells can synthesize cholesterol under normal conditions, most endogenous production occurs in the liver and intestine, from which it is distributed to peripheral tissues by LDL. This arrangement provides an efficient balance between endogenous production and dietary intake of cholesterol. 

Various experiments on animals and humans had shown that cholesterol could either be absorbed from the diet, or if the diet was lacking sufficient cholesterol to meet the body s needs, then it could be synthesized. Cholesterol production within the body is controlled by a feedback mechanism in which cholesterol inhibited the enzyme HMG CoA reductase, an enzyme discovered in 1959 by Feodor Lynen et al. (Figure 1.36) at the Max Planck Institute (Munich).24 ... 

Another heat shock protein-immunophilin chaperone complex is involved in the trafficking of cholesterol.124 A macromolecular complex consisting of FKBP52, caveolin (a 22 kDa protein that plays a role in regulating cholesterol concentration), CyPA, CyP-40, and cholesterol, transports newly synthesized cholesterol from the ER to caveolae. In cells expressing the complex, treatment with either CsA or rapamycin disrupted the complex and interfered with the rapid transport of cholesterol. 

The changes in activity and/or properties of HMG-CoA reductase reported above are, however, accompanied by large changes in enzyme quantity typical of such feeding regimens. These would appear to overshadow any effects due to membrane compositional changes. However, the hypothesis that cholesterol directly feedback-inhibits its own synthesis by altering the catalytic activity of HMG-CoA reductase remains attractive since newly synthesized cholesterol appears preferentially in the smooth endoplasmic reticulum that harbors HMG-CoA reductase [115],... 

It is equally difficult to define in quantitative terms how much newly synthesized cholesterol is present in the intestinal lymph under different physiological circumstances and to determine where such sterol comes from. In theory, such newly synthesized cholesterol could be derived from the intestinal mucosal cells directly or from a more remote organ after either being secreted into the lumen of the bowel or after being delivered to the intestinal villi in plasma lipoproteins. 

Fig. 12. Appearance of newly synthesized cholesterol in mesenteric lymph of the rat. The experimental animals had indwelling lymph fistulae and were infused intraintestinally with a glucose-amino acid-electrolyte solution. One group of these animals was also administered intravenously chylomicrons containing lOS mg of cholesterol, while another group was infused intraduodenally with com oil. 24 h after the initial surgery, each animal was administered [ H]water intravenously and the secretion of labeled cholesterol in intestinal lymph was followed for 18 h. The amount of [ HJwater incorporated into cholesterol was used to calculate the amount of newly synthesized cholesterol present in lymph. These values are expressed as the nmoles of newly synthesized cholesterol secreted into the lymph each hour. The data points represent means +1 S.E.M.

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