Oxysterols Formed Enzymatically

OS are able to regulate key enzymes in CHOL turnover at transcriptional and post-transcriptional levels (Wolf, 1999 Bjorkhem, 2000 Tall et al., 2002). CHOL biosynthesis and homeostasis are regulated by two transcriptional factors steroid regulatory element-binding proteins (SREBP)-1 and -2. These become activated by proteolysis when the CHOL 

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Oxysterols are oxidized forms of cholesterol they are formed enzymatically in the first steps of cholesterol metabolism, and they may also be formed as a result of autoxidation of cholesterol [50]. The high abundance of cholesterol in biological systems means that oxysterols can easily be formed nonenzymatically during sample handling and workup unless care is taken. Oxysterols are biologically active molecules they have been shown in vitro to activate nuclear receptors, for example, liver X receptors (LXRs) [51], to interact with INSIG protein and thereby to repress cholesterol synthesis [52], and, like bile acids, to interact with G-protein coupled receptors. Oxysterols also represent transport forms of cholesterol [53] (Table 2.3). 

Oxysterols are defined as oxygenated derivatives of cholest-5-en-3(3-ol (cholesterol) (Figure 18.1) or precursors of CHOL that may be formed directly by autoxidation or by the action of a specific monooxygenase, or that may be secondary to enzymatic or nonenzymatic lipid peroxidation (Guardiola et al., 1996 Schroepfer, 2000 Bjorkhem and Diczfalusy, 2002). These OS may be formed in the human body by endogenous free-radical attack on CHOL or by enzymatic processes, mainly in the biosynthesis of bile acids and steroid hormones. In addition, OS may be formed exogenously by autoxidation of CHOL in foods. The nomenclature and abbreviations of OS are presented in Table 18.1. It should be emphasized at this point that the OS that occur in... 

A voluminous literature has been published on a wide range of oxidation products of cholesterol because of their potential adverse effects on health and in compromising the safety of various food products (Chapters 12 and 13). This section is limited to the initial hydroperoxides serving as precursors to a complex mixture of oxygenated products, also referred to either as oxysterols or as cholesterol oxides. These products formed either enzymatically or non-enzymatically in biological and food systems will be discussed fiuther in Chapters 11 to 13. 

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