Sterols homeostasis

Duane, W.C. 1993. Effects of lovastatin and dietary cholesterol on sterol homeostasis in healthy human subjects. J. Clin. Invest. 92, 911-918. 

Henneberry, A.L., Sturley, S.L. 2005. Sterol homeostasis in the budding yeast, Saccharomyces cerevisiae. Semin. Cell Dev. Biol. 16 155-161. 

Sturley, S.L. (2000) Conservation of eukaryotic sterol homeostasis new insights from studies in budding yeast. Biochim. Biophys. Acta 1529,155-163. 

Osborne TF. Sterol regulatory element binding protein (SREBPs) Key regulators of nutritional homeostasis and insulin action. J Biol Chem 2000 275 32379-32382. 

Vitamin D is the collective term for a group of compounds formed by the action of ultraviolet irradiation on sterols. Cholecalciferol (vitamin D3) and calciferol (vitamin D2) are formed by irradiation of the provitamins 7-dehydrocholesterol and ergosterol, respectively. The conversion to vitamin D3 occurs in the skin. The liver is the principal storage site for vitamin D, and it is here that the vitamin is hydroxylated to form 25-hydroxyvitamin D. Additional hydroxylation to form 1,25-dihydroxyvita-min D occurs in the kidney in response to the need for calcium and phosphate. A discussion of the role of vitamin D in calcium homeostasis is provided in Chapter 66. 

Mechanism of Action. Like the systemic azoles, clotrimazole and other topical antifungal azoles work by inhibiting the synthesis of key components of the fungal cell membrane that is, these drugs impair production of membrane sterols, triglycerides, and phospholipids.9 Loss of these components results in the membrane s inability to maintain intracellular homeostasis, leading to death of the fungus. 

Members of a family of nuclear transcription factors called sterol regulatory element-binding proteins (SREBP) are responsible for the regulation of these cholesterol feedback mechanisms. SREBP are able to activate a number of genes encoding for proteins involved in the homeostasis of cholesterol and other lipids, including the LDL receptor gene itself. 

A number of cytochrome P450 enzymes are involved in the conversion of acetate to sterols and bile acids (Figure 9.6). The participation of P450 enzymes in pathways of cholesterol biosynthesis and elimination demonstrate their important role in cholesterol homeostasis. Lanosterol 14a-desmethylase, encoded by CYP51A1, is a pivotal P450 involved in cholesterol biosynthesis. The synthesis of bile acids from... 

Meir, K., Kitsberg, D., Alkalay, I., Szafer, F., Rosen, H., Shpitzen, S., Avi, L. B., Staels, B., Fievet, C., Meiner, V., et al. (2002) Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis. J. Biol. Chem. 277, 34036-34041. 

Yang, T, et al. 2002. Crucial step in cholesterol homeostasis sterols promote binding of SCAB to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 110 489-500. 

Weber, L. W., Boll, M., and Stampfl, A. Maintaining cholesterol homeostasis sterol regulatory element-binding proteins. World J Gastroenterol 10 (2004) 3081-3087. 

Yang, T., Espenshade, P. J., Wright, M. E., Yabe, D., Gong, Y., Aebersold, R., Goldstein, J. L., and Brown, M. S. Crucial step in cholesterol homeostasis sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell... 

In mammals, the liver is the organ most active in lipids synthesis, and in this organelle, the transcription factors SREBPs (sterol-regulatory element binding protein) play crucial roles in lipids homeostasis. In addition to cholesterol,... 

Calcium homeostasis is modulated by hormones (Fig. 2). Parathyroid hormone (PTH) is the most important calcium regulator. It is a hormone of 84 amino acids, and is secreted from the parathyroid glands in response to a low unbound plasma calcium. PTH causes bone resorption and promotes calcium reabsorption in the renal tubules, preventing loss in the urine. 1,25-dihydroxycholecalciferol (1.23 DHCC) maintains intestinal calcium absorption. This sterol hormone is formed from vitamin D (cholecalciferol). following hydroxylation in the liver (at carbon-25) and kidney (at carbon-1). However.hydroxylation in the kidney is PTH dependent.andsoeven (he absorption of calcium from the gut relies (albeit indirectly) on PTH. 

---