Lynen begins the present lecture by pointing out some fundamental, but often misconceived facts about the relation of nutritional fat and body fat. Compared to carbohydrates and proteins, fats have the highest energy content, Lynen says: a gram of fat contains more usable energy than a gram of sugar, approximately double. For this reason, fat rich diets are also energy rich and can in fact promote weight gain, i.e. the build-up of adipose (fatty) tissue or the colloquial “fat pads”. This is one of the ways by which our bodies achieve long term energy storage.
However, the growth of “fat pads” can also be sustained by carbohydrates and proteins. So even if one would follow a completely fat free diet, one could still, quite easily, “fatten up”. What counts is the total energy intake. This is due to our body’s ability to biosynthesize fats from very small, universal building blocks, which can be derived from proteins as well as from sugars, Lynen points out.
He then goes on to discuss the chemical details of the biochemical synthesis of fats, a truly amazing process. The long hydrocarbon chains (usually 16 or 18 carbon atoms long) of fatty acids are successively made from several acetic acid molecules. These are the universal building blocks mentioned above. Acetic acid is an intermediate in energy metabolism and contains only two carbon atoms. Before it can be used for the synthesis of fatty acids, it needs to be activated. This is done by esterification to a molecule of coenzyme A.
The special feature of this esterification is that it yields an energy rich, unstable thioester, the so called S-Acetyl-Coenzyme A. A molecule of S-Acetyl-Coenzyme A equals an activated two carbon atom building block. By virtue of a multi-enzyme complex several of these building blocks are then used to construct the fatty acid. This process takes place in adipose tissue and the liver. The insight, that acetic acid is activated by means of a thioester is one of the early results that gained Lynen’s laboratory international recognition.
In the last part of his talk, Lynen discusses the regulation of fatty acid synthesis and metabolism, pointing out that our body uses several feedback loops to control how much fatty acids are made. On the one hand, fatty acid synthesis is responsive to the availability of citric acid. Only if the latter is abundantly available, new fatty acids are made. Since a high concentration of citric acid indicates a high rate of energy metabolism, this feedback loop helps to ensure that fatty acids are only made if excess energy is available. On the other hand, fatty acid synthesis is controlled by its own end products. If too much fatty acids are made, the synthesis rate is slowed down to avoid an excessive build-up.