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Tuesday, November 13, 2007

How to Make Cholesterol

Monday's Molecule was squalene, a thirty carbon lipid with a characteristic set of double bonds [Monday's Molecule #51]. Most species can synthesize squalene. In some, it serves as the precursor for biosynthesis of cholesterol and other complex steroids.

Cholesterol is an essential component of cell membranes and the initial substrate in pathways leading to hormones such as testosterone and β-estradiol.

A brief outline of the pathway from squalene to cholesterol is shown on the right. The first thing to note is that squalene can fold into a form that already resembles cholesterol. The reactions in the pathway result in closing the rings to make the four ring structure that's characteristic of steroids.

Lanosterol is a key intermediate in this pathway. Note that in addition to the ring closing reactions, an oxygen—in the form of a hydroxyl group—has been added to the ring.

The conversion of lanosterol to cholesterol requires up to 20 enzyme-catalyzed steps. There's more than one way to make cholesterol from lanosterol but in the end all molecules of cholesterol are identical.

Most species, including humans, are capable of synthesizing all the cholesterol they will ever need. In animals, the biosynthesis pathway is regulated by the amount of cholesterol in the blood plasma. If a large amount of cholesterol is derived from food then the biosynthesis pathway is down-regulated to compensate.

1 comment :

  1. Just getting around to this one, but that squalene molecule twisted around into a cholesterol shape is the coolest thing I've seen since, well since that new herbivorous dinosaur skull this morning.