Cholesterol

Cholesterol is a type of fat-like substance found in all animals, making up a key part of their cell membranes and helping cells communicate. It is especially concentrated in the brain and spinal cord, as well as in animal fats and oils. Every animal cell can produce its own cholesterol, though in vertebrates the liver makes the most. In the brain, support cells called astrocytes manufacture cholesterol and deliver it to neurons. Bacteria and archaea generally lack cholesterol, with a few exceptions like *Mycoplasma*, which need it to grow. The body uses cholesterol as a starting material to make steroid hormones, bile acid, and vitamin D. Having too much cholesterol in the blood, particularly when carried by low-density lipoprotein (LDL), is linked to a higher chance of developing cardiovascular disease. The compound was first isolated in solid form from gallstones in 1769 by François Poulletier de la Salle, and chemist Michel Eugène Chevreul gave it the name "cholesterine" in 1815. The word itself comes from Greek roots meaning "bile" and "solid," plus the chemical suffix for an alcohol.

Cholesterol is vital for all animal life. Although most cells can make it, the liver produces the bulk, and it is then transported through the blood to other cells. The amount of cholesterol in tissues depends on a balance between how much is taken in and how much is exported. In a healthy brain, cholesterol is kept separate from the rest of the body—dietary and liver-made cholesterol cannot cross the blood-brain barrier. Instead, astrocytes in the brain make and distribute cholesterol locally. Making cholesterol from scratch is a complex 37-step process. The first 18 steps are known as the mevalonate or HMG-CoA reductase pathway, which is targeted by statin drugs. The remaining 19 steps turn lanosterol into cholesterol. A typical 68-kilogram man produces about one gram of cholesterol daily and carries roughly 35 grams in his body, mostly in cell membranes. In the United States, a man’s average daily intake from food is about 307 milligrams. Most dietary cholesterol is esterified, making it hard for the gut to absorb. The body also cuts back its own production when it absorbs cholesterol from food, so eating cholesterol has little effect on blood levels seven to ten hours later. In rats, eating more cholesterol actually lowers blood cholesterol. For the first seven hours after a meal, as fats are transported by lipoproteins, blood cholesterol levels rise temporarily. Plants make only tiny amounts of cholesterol but produce larger quantities of phytosterols, which are chemically similar. These phytosterols compete with cholesterol for absorption in the intestines, and if absorbed, the gut usually sends them back out. People typically get 200 to 300 milligrams of phytosterols per day from their diet, and specially designed vegetarian meals can provide over 700 milligrams.

Cholesterol is found in all animal cell membranes but not in prokaryotes. It helps build and maintain membranes and adjusts how fluid they are across normal body temperatures. Each cholesterol molecule has a hydroxyl group that interacts with water, while its steroid rings and hydrocarbon chain sit among the fatty acids of other membrane lipids. This arrangement tightens membrane packing, changing fluidity and keeping the membrane strong without needing a cell wall. The result is a stable yet flexible membrane that allows animal cells to change shape and animals to move. The rigid, flat structure of cholesterol’s rings also reduces the membrane’s permeability to neutral molecules, hydrogen ions, and sodium ions.

Cholesterol also plays a role in substrate presentation, a process that activates certain enzymes. One example is phospholipase D2 (PLD2). This enzyme gets palmitoylated, which sends it to cholesterol-rich areas of the membrane called lipid rafts. Its substrate, phosphatidylcholine (PC), is scarce in these rafts and instead sits in disordered regions along with another lipid, PIP2. PLD2 has a binding site for PIP2. When PIP2 levels rise, PLD2 leaves the cholesterol-rich domains, binds to PIP2, and then gains access to its substrate PC to begin its catalytic work.