Triglycerides, Cholesterol Esters and a Tip from Sherlock Holmes.

The most common lipid in our bodies is triglyceride and cholesterol commonly occurs as a fatty acid ester. (And in some of us these compounds are more common than we would like!) Yet neither is found in biological membranes. Why not? Why are diglycerides and cholesterol necessary components of plasma membranes, but the closely related triglycerides and cholesterol esters never present?

Like Sherlock Holmes, who solved one of his more famous cases thinking about a hound who didn't bark in the night, scientists often gain very useful information analysing patterns of absent elements as well as ones that are present.   Exactly how do triglycerides and cholesterol esters differ from diglycerides and cholesterol?

In contrast with membrane lipids, triglycerides and cholesterol esters are entirely hydrophobic; for this reason they are often called neutral fats. They readily associate with each other, or other hydrophobic molecules, and often form large droplets or spherical bodies inside cells. They are not soluble in cytoplasm or other aqueous solutions, although they will dissove in organic solvents. In contrast, diglycerides and cholesterol interact with water just like polar solute molecules, and they readily associate with each other (like their neutral kin). Their hydrophobic property prevents them from dissolving in aqueous solutions, however, and their polarity prevents them from forming large, amorphous fat droplets. Such seemingly contradictory behavior is exactly what is meant by "amphipathic" and is crucial for the ability of phospholipids to form membranes, as we shall investigate in greater detail in Section 3.

2. The Lipid Nature of Biological Membranes.

Lipids make up the bulk of biological membranes, and it's reasonable to suppose their large numbers greatly influence membrane structure and function. Indeed, it's not too far-fetched to say membrane lipids and their interactions "create" biological membranes. How do such small molecules exert such a large role? To answer this question we need to examine the structure of lipids themselves.

Phospholipid MoleculesMost cellular lipids are derived chemically from the three-carbon alcohol, glycerol, through covalent linkages with up to three fatty acids. Specifically, a fatty acid may form an ester with each of glycerol's three alcohol residues, and the resulting lipids are called glycerides All membrane glycerides have fatty acid (hydrocarbon or acyl) residues attached to two adjacent glycerol carbons and a polar, often charged, residue linked covalently with the third carbon, and are called diacyl glycerides or simply diglycerides. Diglycerides containing phosphate as part of the polar residue are called, not surprisingly, phospholipid. Another major plasma membrane lipid is cholesterol. Different structural representations of these two membrane lipids are presented on the facing page. Note in particular, that both types of molecules consist of regions that are hydrophilic, or water-loving, and hydrophobic, or water-hating.

This schizophrenic nature of membrane lipids seems to be no accident! Scroll through the Table of Membrane Lipids on the next page and note all of the more common forms share this important feature: all membrane lipids have a hydrophobic region as well as a hydrophilic one. The long hydrocarbon chains of the fatty acids (or the fatty-acid like residues) projecting to the left of each lipid will not spontaneously interact with dipolar water molecules (or readily dissolve in aqueous solutions). Conversely, the different residues projecting to the right of each lipid are all polar and will readily interact with water. More technically, membrane lipids are called amphipathic molecules, because they possess distinct regions with such different affinities for oil and for water. Even the very hydrophobic and insoluble cholesterol is slightly amphipathic, by virtue of its single alcohol residue.

The amphipathic nature of membrane lipids contrasts strikingly with the neutral triglycerides and cholesterol esters which are more abundant in our bodies than their amphipathic relatives.

How do you think these amphipathic molecules would behave if their concentrations were increased in an aqueous environment? in an organic solvent? at the interface between an aqueous and an organic solvent? Go on to the next page to consider the formation of lipid structures called micelles.