Cholesterol pathway

The reverse cholesterol pathway is mediated by HDL. HDL is formed from precursor particles originating from the intestine and the liver. In addition, surface... 

Figure 6.4 De novo synthesis of cholesterol. Pathway of cholesterol biosynthesis. Synthesis begins with the transport of acetyl-CoA from the mitochondrion to the cytosol. The rate-limiting step occurs at the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase catalysed step. The phosphorylation reactions are required to solubilise the isoprenoid intermediates in the pathway. Intermediates in the pathway are used for the synthesis of prenylated proteins, dolichol, coenzyme Q and the side chain of haem a.

Much of the prior discussion has focused upon statin effects on cholesterol pathways. However, recent data suggest statin benefit in AD may occur via mechanisms completely independent of cholesterol lowering. For example, samples are known to modulate isoprenylation pathways and have potentially very potent anti-inflammatory activities [161]. Indeed, inhibition of proteins that are dependent upon isoprenylation, such as the Ras GT-Pase superfamily, has been suggested to be an import step in the inhibition of iNOS stimulated cytokine release [161]. In order to better understand... 

HDL is antiatherogenic and removes cholesterol from peripheral cells and tissues for eventual transport to hepatocytes and excretion in the bile directly or after conversion into bile acids. The efflux of cholesterol from peripheral cells is mediated by the ATP-binding cassette (ABC) transporter protein (discussed later). The flux of cholesterol transport from extrahepatic tissues (e.g., blood vessel wall) toward liver for excretion is known as the reverse cholesterol transport pathway. In contrast, the forward cholesterol pathway involves the transport of cholesterol from liver to the peripheral cells and tissues via the VLDL IDL LDL pathway. It should be noted, however, that the liver plays a major role in the removal of these lipoproteins. Thus, the system of reverse cholesterol transport consisting of LCAT, CETP, apo D, and their carrier lipoproteins is critical for maintaining cellular cholesterol homeostasis. The role of CETP is exemplified in clinical studies involving patients with polymorphic... 

Isopentenyl pyrophosphate and other Isoprenold Intermediates In the cholesterol pathway also serve as precursors for more than 23,000 biologically active molecules. Some of these molecules are discussed In other chapters various hemes. Including the oxygen-binding component of hemoglobin and electron-carrying components of cytochromes (see Figure... 

Nelson TJ, Alkon DL (2005) Insulin and cholesterol pathways in neuronal function, memory and neurodegeneration. Biochem Soc Trans 33 1033-1036 Nicotera P, Lipton SA (1999) Excitotoxins in neuronal apoptosis and necrosis. J Cereb Blood Row... 

Bartley, G.E., Yokoyama, W, Young, S.A., Anderson, W.H.K., Hung, S.C., Albers, D.R., Langhorst, M.L., Turowski, M., Hyunsook, K.H. Hypocolesterolemic effects of hydroxypropylmethylcellulose are mediated by altered gene expression in hepatic bile and cholesterol pathways of male hamsters. J. Nutr. 

This study demonstrated that the Pu-Erh tea contained lovastatin in a low, but yet detectable amount. The aqueous extract of Pu-Erh tea (PET) inhibited cholesterol biosynthesis in cultured human hepatoma cells (Hep G2). PET did not affect post-mevalonate events in the cholesterol pathway, since the incorporation of labeled mevalonate into cholesterol was not affected. Direct evidence to support the occurrence of lovastatin in PET was based on extensive purification and identification of lovastatin in its lactone form by mass spectrometry. To enrich lovastatin, PET was solvent extracted to recover lovastatin in lactone form. The content of lovastatin in Pu-Erh tea varied greatly among different batches. The situation is not unexpected, since the preparation procedure of Pu-Erh tea involves natural fermentation. The growth of Aspergillus and production of lovastatin in Pu-Erh tea during the fermentation and storage is not under control. 

Cholesterol regulates its own formation by inhibiting the transcription of several genes in the cholesterol pathway, most notably HMG-CoA synthase and HMG-CoA reductase. For many years it was also known that polyunsaturated fats decrease the level of cholesterol synthesis. Now we know how these regulatory events occur. 

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