The basic structure of phospolipids is very similar to that of the triglycerides except that C–3 ( sn 3)of the glycerol backbone is esterified to phosphoric acid. The building block of the phospholipids is phosphatidic acid. Substitutions that can be added to phosphatidic acid include ethanolamine (phosphatidylethanolamines, PE), choline (phosphatidylcholines, PC: also called lecithins), serine (phosphatidylserines, PS), glycerol (phosphatidylglycerols, PG), myo -inositol (phosphatidylinositols, PI: these compounds can have a variety in the numbers of inositol alcohols that are phosphorylated generating polyphosphatidylinositols), and phosphatidylglycerol (diphosphatidylglycerols, DPG; more commonly known as cardiolipins). See the Lipid Synthesis page for images of the various phospholipids.
Ask students what materials their bodies are made out of (Proteins: Hair, fingernails, muscles, tendons, cartilage, enzymes, antibodies, hemoglobin, hormones, etc.), fats (cell membranes, insulating layer around nerve cells, steroids, etc.) and carbohydrates (energy source = blood sugar, stored as glycogen in liver and muscles etc.). Discuss where we get the materials from to build this structures and molecules inside of our bodies (through our food!). Have students brainstorm sources of proteins, carbohydrates and fats in their diet. Tell students that they will test various food items for the presence of these three macromolecules.
Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the homeostatic mechanisms involved are only partly understood. A higher intake from food leads to a net decrease in endogenous production, whereas lower intake from food has the opposite effect. The main regulatory mechanism is the sensing of intracellular cholesterol in the endoplasmic reticulum by the protein SREBP (sterol regulatory element-binding protein 1 and 2). In the presence of cholesterol, SREBP is bound to two other proteins: SCAP (SREBP-cleavage-activating protein) and Insig1. When cholesterol levels fall, Insig-1 dissociates from the SREBP-SCAP complex, allowing the complex to migrate to the Golgi apparatus, where SREBP is cleaved by S1P and S2P (site-1 and -2 protease), two enzymes that are activated by SCAP when cholesterol levels are low. The cleaved SREBP then migrates to the nucleus and acts as a transcription factor to bind to the SRE (sterol regulatory element), which stimulates the transcription of many genes. Among these are the low-density lipoprotein (LDL) receptor and HMG-CoA reductase. The former scavenges circulating LDL from the bloodstream, whereas HMG-CoA reductase leads to an increase of endogenous production of cholesterol. A large part of this signaling pathway was clarified by Dr. Michael S. Brown and Dr. Joseph L. Goldstein in the 1970s. In 1985, they received the Nobel Prize in Physiology or Medicine for their work. Their subsequent work shows how the SREBP pathway regulates expression of many genes that control lipid formation and metabolism and body fuel allocation. Cholesterol synthesis can be turned off when cholesterol levels are high, as well. HMG CoA reductase contains both a cytosolic domain (responsible for its catalytic function) and a membrane domain. The membrane domain functions to sense signals for its degradation. Increasing concentrations of cholesterol (and other sterols) cause a change in this domain's oligomerization state, which makes it more susceptible to destruction by the proteosome. This enzyme's activity can also be reduced by phosphorylation by an AMP-activated protein kinase. Because this kinase is activated by AMP, which is produced when ATP is hydrolyzed, it follows that cholesterol synthesis is halted when ATP levels are low  .