Glycerides Monday, May 6 2013
Recently, I have had a few requests to write a post about glycerides. It really is a good idea as these molecules have important jobs to do, but are also a building material for several other lipids. In fact, the majority of lipids and fats are either glycerides, or can be made from them. What I am going to do here is go through a few basics and then give an example of what they can do.
The first thing to know is that glycerides come in three different sorts: monoglycerides, diglycerides and triglycerides (Fig. 1). These are also sometimes called mono- di- and tri-acylglycerols, respectively.
The most common glycerides are probably triglycerides, so I will discuss those first. Triglycerides are fats or oils* but not lipids, as they are not amphiphilic. Be warned, though: plenty of people lump them in with lipids anyway. However, for the avoidance of doubt I shall continue to refer to them as fats if they are saturated (like the ones from butter or lard), or oils if they are unsaturated (like the ones from olive or sunflower oil). Whatever you call them, and however they are classified, one thing is not in doubt: triglycerides are the most concentrated way terrestrial life-forms have of storing energy. This energy store can be quantified, it stores 9 kcal/g. Energy can be stored as protein and carbohydrate, but this is never quite as concentrated as fats. Triglycerides have been found in pretty much every type of living organism yet discovered – certainly in plants, insects, fungi and animals. There is less need for bacterial and archaea species to store energy as higher life-forms do, so the quantities in evidence there are much lower.
Monoglycerides are the least common of the three types in biological systems, and are often intermediates in the metabolism of triglycerides. They have some peculiar physical properties that have been explored in a number of research papers (others include this one and this one). What that work has shown, is that the sorts of lipids found in biological systems can adopt certain morphologies; in a sense, it has shown us what sorts of shapes and contortions are ‘possible’ with these types of lipid. This has implications for what we observe in the physical process of cell division, as data like this can allow us to identify the physical behaviour of individual lipids. This allows us to start the process of ‘who is doing what’ on a molecular level, during processes such as cell division.
Diglycerides are perhaps the most interesting because they exist in nature as shown above and are also a building block for many other biological lipids. They are amphiphilic by virtue of the hydroxyl group (polar end) and the two fatty acid residues (lipophilic end). However, the polar end is not quite polar enough to make diglycerides self-assemble on contact with water, unless they are mixed with other lipids, like phosphatidylcholine (PC). This places diglycerides in a peculiar sort of physical purgatory, where they are not really lipids in the classical sense, but are not fats either. Cholesterol also falls into this category as it too forms part of a biological membrane, but will not form a membrane in its own.
Adding a simple phosphate group to a diglyceride turns it in to phosphatidic acid (PA). This will self-assemble on its own on contact with water, and is the simplest common phospholipid. Further chemical elaboration of PA gives rise to the majority of biological amphiphiles. One particularly interesting one I like is called PIP2. The full name for this particular lipid is phosphatidylinositol-4,5-bisphosphate. You can see that the name is built up from ‘phosphatidyl’ (referring to the PA part), ‘inositol’ because it contains an inositol structure, called an inositol moiety, and ‘bisphosphate’ because it contains two phosphates not joined to the glyceride. This lipid is special because it is not just part of the membrane, but also a signalling lipid. We know this for several reasons, one of which is that when it is hydrolysed (cut in half), it gives rise to two molecules that go on to have other functions.
PIP2 is hydrolysed into IP3 and a diglyceride. In cells, IP3 is the trigger for the release of calcium ions from intracellular storage. The effects of this are as varied as muscle contraction and some of the early events of fertilisation. Cell type is therefore important in knowing what this signal does.
The diglyceride activates an enzyme called PKC. This enzyme phosphorylates a number of other proteins, ensuring that they are ‘switched on’. This leads to a number of carefully controlled effects, including smooth muscle contraction in the digestive system, muscle contraction that causes ejaculation and the secretion of saliva, and aggregation of blood platelet cells. PKC also activates the proteins that are involved in neuronal activity in the brain.
This variety of bodily responses means that tight control mechanisms are required at a cellular level in order that the incorrect effect is not initiated**. The thing that strikes me about this is that the effects we observe of both the signalling molecules the come from PIP2, and the different glycerides, show just how closely our cells can control all of these molecular species – enough for us not to have any conscious idea that digestive, ejaculatory and neuronal effects are triggered by the same chemical process. Further, that such similar molecules can be both an energy storage facility and a means of digesting our food.
* The difference between fats and oils is that at room temperature, oils are liquids and fats are solids. This is related to the number of unsaturated bonds in the fatty acid residues.
** Some current research is focussed on what happens when such signalling goes wrong, and on how to treat this medically.