title: Speculations on the evolution of sterol structure and function.
abstract: The essential oxygen requirement for sterol biosynthesis dates this molecule as a relative latecomer in cellular evolution. Structural details of the cholesterol molecule and related sterols can be rationalized in terms of optimal hydrophobic interactions between the planar sterol ring system and phospholipid acyl chains in the membrane bilayer. The prediction that the cholesterol precursor lanosterol (4,4',14 trimethyl cholastadienol) is incompetent for membrane function is verified by in vivo experiments with eucaryotic sterol auxotrophs and microviscosity measurements of sterol-containing artificial membranes. For procaryotic cells the sterol specificity is very much broader. Methylococcus capsulatus produces 4,4-dimethyl- and 4-monomethyl sterols, but not sterols of the cholesterol type. Similarly lanosterol and its partially demethylated derivatives satisfy the sterol requirement of Mycoplasma capricolum. A more primitive but unspecified role of cyclized squalene derivatives is therefore postulated for procaryotic membranes. The finding that cholesterylmethyl ether satisfies the sterol requirement of certain microbial systems is at variance with current views on the role played by the sterol hydroxyl group in membrane organization and function.
mesh_terms: D005075:Biological Evolution; D019605:Euryarchaeota / Q000378:metabolism; D007810:Lanosterol; D008081:Liposomes; D008567:Membranes, Artificial; D009174:Mycoplasma / Q000378:metabolism; D010100:Oxygen; D010713:Phosphatidylcholines; D013261:Sterols / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D008081:Liposomes; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D013261:Sterols; D007810:Lanosterol; D010100:Oxygen