Skip to Main Content

OVERVIEW

Lipids perform several essential functions, including forming biological membranes, efficient storage of energy, and as components of several important structural and functional molecules. Lipid metabolism includes both the synthesis and degradation of fatty acids and/or more complex lipid molecules. The choice between synthesis and degradation represents an important regulatory step in human biology and reflects the level of food and, therefore, energy stores available to the body. Several processes are involved in this decision of producing fatty acids/lipids or, instead, directing their precursors to energy production via carbohydrate metabolic pathways. Separate but still dependent on this process, the production of cholesterol and several lipid-derived hormones and signaling molecules is essential for multiple functions in the human body. As in most metabolic pathways, deficiencies or problems can lead to serious disease states. As seen in other chapters, understanding of the exact mechanism of these problematic metabolic steps also allows treatment of these diseases.

FATTY ACID METABOLISM

FATTY ACID SYNTHESIS

Although most fatty acids needed by humans are supplied in the diet, fatty acid synthesis plays a role in certain tissues to convert any excess of sugar molecules into the more efficient storage form of fatty acid/lipid molecules and/or to produce specialized lipid molecules. The link between sugar and fatty acid/lipid metabolism is seen at acetyl coenzyme A (CoA), the intermediate between glycolysis and the citric acid cycle. As will be seen below, acetyl-CoA is also the initial molecule of fatty acid metabolism. Therefore, acetyl-CoA is an important branch point of human metabolism and its use is highly controlled to reflect the body’s nutritional state and needs. As an illustration of this fact, the first and committing step of fatty acid synthesis is the addition of a carboxyl (CO2) group, donated by HCO3, to acetyl-CoA to produce malonyl-CoA.

Although the reaction is simple, the choice to commit the potential energy production from carbohydrates to produce lipid molecules reflects several important biological principles in human metabolism. First, the enzyme that catalyzes this reaction, acetyl-CoA carboxylase, is produced as smaller, inactive protein complexes. When the concentration of citrate is high (the first intermediate of the citric acid cycle and a sign of abundant sugar resources), these smaller complexes join to form active enzymatic polymers (Figure 7-1). Therefore, citrate increases fatty acid synthesis when the body has plentiful energy and needs to store this energy in an efficient fashion. If lipid stores are high, though, increased concentration of palmitoyl-CoA (the final product of fatty acid synthesis) decreases fatty acid synthesis by depolymerizing the active enzyme complex into the original smaller, inactive complexes. The balance between citrate and palmitoyl-CoA or, more simply, a measure of sugar versus fat levels (e.g., high sugar/fat indicates plentiful food supplies; low ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.