In addition to fats, phospholipids, and sphingolipids, cholesterol is another lipid with crucial biological functions. Even though prejudice associated with cardiovascular diseases, its roles in cell structure, hormone synthesis, vitamin metabolism and bile acid production are equally important.
Structure and Physicochemical Properties of Cholesterol
| Cholesterol and sterol | ||
|---|---|---|
| Feature | sterol | cholesterol |
| Core Structure | Four-ring carbon backbone (A、B、C、D) | Four-ring carbon backbone (A、B、C、D) |
| Function Group | Various substituents and side chains, different steroids have different functional groups | There is a hydroxyl group at C-3, an eight-carbon side chain at C-17, and a double bond between C-5 and C-6. |
| Functions | Plants, fungi cell membrane structure, hormones, antioxidants | Animal cell membrane structure, which is the precursor of steroids |
The structure is significantly different from fats and phospholipids. The core of cholesterol contains three six-membered carbon rings and one five-membered carbon ring. The function groups are positioned in its core. A hydrophilic hydroxyl attached to the first six-membered ring. A double bond is in the second six-membered ring. A hydrocarbon chain extends from to the five-membered ring. It is obvious that hydrophilic groups are rare and hydrophobic structure is in dominance, so cholesterol is virtually water insoluble and soluble in organic solvents. It’s a white or slightly yellow waxy solid at room temperature.
The double-bond renders cholesterol susceptible to oxidation. In vivo, it’s easily oxidized by reactive oxygen species (ROS) generated during metabolism. The superoxide (O₂⁻) and hydrogen peroxide (H₂O₂) are common ROS. In vitro, exposure to ultraviolet light or oxygen can also degrade cholesterol.
It is widely distributed in animals particularly mammals although its levels vary among different species and tissues. Generally speaking, fatty tissues contain the most cholesterol followed by lean meat and poultry products. Shellfish and mollusks have higher cholesterol levels than fish. The richest sources are yolk, fish roe and animal organs.
Sterols have a similar structure and physicochemical properties. They also have three six-membered carbon rings and one five-membered carbon ring, but differ in their side chains and functional groups.
Cholesterol, Sterols in Cell Membranes
It stabilizes the cytoplasmic membrane and prevents leakage of water-soluble substances through lipid bilayer. Cholesterol can’t form a lipid bilayer but inserts into phospholipid bilayers to become part of cell membranes. Depending on different conditions, it either increases or decreases membrane fluidity. At low temperatures, phospholipids will arrange tightly to make the membrane rigid and less fluid. Cholesterol enlarges the phospholipid gap to rise membrane fluidity. Conversely, membranes become too fluid and disordered at high temperatures. Cholesterol grows the tail by attaching to phospholipid head. This effect stabilizes the membrane by increasing molecular interactions. Notably, this elongation occurs in the glycerophospholipids, but don't in sphingolipids.
Cholesterol and sphingolipids form lipid rafts in the cell membrane to provide a stable and rigid platform. Specific membrane proteins and signaling molecules are enriched on lipid rafts to perform their functions, such as signal transduction, substance transport and biochemical reactions. It’s primarily synthesized in smooth endoplasmic reticulum, though some cholesterol is also from diet. In cells, most cholesterol is found in membranes system. Additionally, cytoplasm and blood also contain some cholesterol that form spheres with proteins (LDL, HDL) that facilitate the receptor-mediated endocytosis or exocytosis.
There is no cholesterol in plant and fungal cells, but some similar compounds called sterols. Similar functions to cholesterol make them a component of cell membranes. In plant plasma membranes, sterols constitute about 5% to 25% of total lipids. The structure and biosynthetic pathways of sterols and cholesterol are slightly different, so it’s basis for antifungal drugs.