Oxysterols

What are Oxysterols?

Oxysterols are oxidized derivatives of cholesterol with important functions in many biological processes, including cholesterol homeostasis, atherosclerosis, nerve sphingolipid metabolism, platelet aggregation, apoptosis, and protein isoprenylation. Oxysterols are usually formed because cholesterol is readily oxidized. First, C7 loses its hydrogen atom and becomes a free radical, which reacts with hydroxide to form hydroperoxide. Then, the hydroperoxide destroys the double oxygen bond to form hydroxycholesterol, and then dehydrogenates to form oxidized cholesterol. The oxidation of cholesterol can result in more than 70 different cholesterol oxidation products. BOC Sciences offers a wide range of oxysterols and qualitative and quantitative analysis of related substances.

Fig. 1. Schematic representation of synthesis of some oxysterols (Cells. 2021, 10(9): 2301).

Examples of Oxysterols

24-Methylenecholesterol

24-Methylenecholesterol is a naturally occurring marine sterol that stimulates the enzyme cholesterol acyltransferase in human macrophages. 24-Methylenecholesterol uniquely combines the inhibition of cholesterol synthesis in the liver with accelerated excretion of cholesterol, resulting in a reduction of cholesterol in the body. 24-Methylenecholesterol is a natural marine sterol that stimulates cholesterol acyltransferase in human macrophages.

Cholesterol β-D-Glucoside

Cholesterol β-D-glucoside is a derivative of cholesterol that contains β-D-glucose. It is formed from cholesterol and glucosylceramide by β-glucosidase 1. It is a lipid mediator in the heat stress response of animals and has antiulcerogenic effects. It activates heat shock transcription factor 1 (Hsf1) in response to heat shock and increases the expression of heat shock protein 70 (Hsp70) in TIG-3 human fetal lung fibroblasts when used at a concentration of 10 μM.

7β, 27-dihydroxy Cholesterol

7β, 27-dihydroxy Cholesterol is an oxysterol and an agonist of the retinoic acid receptor-related orphan receptor gamma (RORγ) and RORγt. It activates RORγ- or RORγt-dependent signaling in reporter gene assays using HEK293T cells expressing the recombinant human receptor with EC 50 values of 691 and 1,045 nM, respectively.

Oxysterol Synthesis

Step 1 - Cholesterol side chain oxidation is the first step in oxidative cholesterol synthesis, and this step involves catalysis by a member of the cytochrome P450 enzyme family in the cytoplasm. This enzyme converts cholesterol to 20, 22-dihydroxycholest-4-en-3-one by catalyzing the side chain oxidation of cholesterol.

Step 2 - Sterol side chain dehydrogenation is then carried out to convert 20, 22-dihydroxycholest-4-en-3-one to 3-hydroxycholest-4-en-20-one.

Step 3 - After completing the dehydrogenation of the sterol side chain, a cyclization reaction is also required to form the structure of bile acids.

Step 4 - Finally, the resulting compounds are converted to the target oxidized cholesterol, such as bile acids or cholesterol, through further chemical synthesis or specific enzyme-catalyzed reactions.

Oxysterol Function

Antioxidant effects. Some oxidized cholesterol has antioxidant activity, which can neutralize free radicals and oxidative stress products, reducing oxidative damage and oxidative destruction of cell membranes.

Cell membrane structure. In the cell membrane, oxidized cholesterol interacts with other lipid molecules, affecting the fluidity and stability of the cell membrane and the function of receptors.

Involved in steroid hormone synthesis. Oxidized cholesterol is a precursor for the synthesis of steroid hormones. They are further converted into physiologically active hormones in the adrenal and reproductive systems, where they are involved in the regulation of metabolism, reproductive development, and the formation of sexual characteristics.

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Reference

1. Freitas, F.A. et al. Impact of oxysterols on cell death, proliferation, and differentiation induction: Current status. Cells. 2021, 10(9): 2301.