Cholesterol is an important constituent of the cell membrane of most eukaryotic cells, in myelin formation in the brain, spinal cord, and peripheral nervous system, and acts as the precursor for steroid hormones and bile acids. The pathway of cholesterol synthesis is quite elaborate. Starting with activation of HMGCoA reductase by acetylCoA, through the conversion of mevalonate to squalene (C30) by several rounds of “polymerization”, cyclization of squalene yields the first cholesterol intermediate. Then demethylation, desaturation and saturation reactions convert lanosterol to cholesterol.
There are many instances where metabolic defects can halt this process and impair the usual concentration of cholesterol in the organism. Impaired cholesterol synthesis has been linked to psychomotor retardation, developmental delay, structural brain malformations, multiple congenital anomalies, and microcephaly. Impaired cholesterol biosynthesis has also been implicated in autism and other behavioral disorders.
Sitosterolemia is a rare disease involving structurally similar plant sterols. These sterols can be taken up from the human gut lumen but not extruded. They make their way into the blood system via cholymicrons and can lead to atherosclerosis and fat depot in the skin.