Lipid Metabolism Overview

Lipid Metabolism

• Lipids are a diverse group of compounds sharing the common characteristic of insolubility in water.
• Lipids are hydrophobic.
• Biological functions of lipids include storage of energy, structural elements of biological membranes, hormones, intra- and extracellular signaling, and protection of internal organs.
• Key forms of lipids include fatty acids, glycerol, triglycerides, phospholipids, sterols, vitamins (A, E, D, K).
• Fatty acids range from 4 to 36 carbons in length.
• Saturated fatty acids have no double bonds while unsaturated fatty acids have one or more double bonds.
• Classification of lipids is based on their structure (simple vs complex).
• Simple lipids cannot be divided into simpler units while complex lipids can be divided into simpler structural units. Examples of simple lipids include fatty acids, terpenes, sterols, eicosanoids. Examples of complex lipids are acylglycerides, phosphoacylglycerides, sphingolipids, waxes.
• Acylglycerides are composed of 1, 2, 3 fatty acids linked to a glycerol molecule. Types of acylglycerides include monoacylglycerides, diacylglycerides, and triacylglycerides.
• Triacylglycerols are the primary stored form of energy in adipose tissue.
• Sterols, like cholesterol, are structural lipids in cell membranes and precursors for steroid hormones.
• Cholesterol is amphipathic, having a polar head group (-OH) and a nonpolar hydrocarbon body.
• Cholesterol is a precursor to steroid hormones like estrogens, testosterone, progesterone, and cortisol as well as bile acids which emulsify dietary fats.
• Cholesterol is also important for vitamin D synthesis and plays a role in the transport of lipids in the blood.

Digestion and Absorption of Lipids

• Dietary lipids (triacylglycerols) form droplets in the stomach.
• Bile salts secreted from the gallbladder emulsify lipids.
• Lipases secreted from the pancreas convert triacylglycerols into fatty acids and monoacylglycerols.
• Digestion products are carried as micelles to the intestinal epithelium cells.
• Triacylglycerols are reformed from the free fatty acids and monoacylglycerol.
• Lipoproteins (chylomicrons) are formed and transport triacylglycerols to tissues.

Transport of Lipids in the Blood

• Lipoproteins are macromolecular complexes of specific carrier proteins and various combinations of lipids.
• Proteins solubilize lipids and direct them to specific targets.
• Lipoprotein types include chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL).
• Chylomicrons transport dietary lipids from the intestines to the liver.
• VLDL transports triglycerides synthesized in the liver to other tissues.
• LDL carries cholesterol from the liver to other tissues.
• HDL reverse cholesterol transport. They pick up cholesterol from extrahepatic tissues and return it to the liver.

Lipid Storage

• Triacylglycerols are stored in adipocytes (fat cells) in lipid droplets when more fatty acids are consumed than needed.
• When energy is needed, triacylglycerols in adipose tissue are broken down and transported to tissues needing energy.

Lipid Removal

• Fatty acids stored in adipose tissue are converted into energy in three stages.
• Stage 1: Mobilization of triacylglycerols in adipose tissue, stimulated by hormones like epinephrine (fight or flight) and glucagon (fasting). Hormone-sensitive lipase (HSL) hydrolyzes triacylglycerols into fatty acids and glycerol which then enter the bloodstream.
• Stage 2: Activation of fatty acids and transport into the mitochondria. The fatty acids are activated to fatty acyl-CoAs and transported into the mitochondria via the carnitine shuttle.
• Stage 3: Degradation of fatty acids to acetyl-CoA, which is processed by the citric acid cycle for energy production.

Fatty Acid Synthesis

• Fatty acids are synthesized from acetyl-CoA derived from glucose or amino acids.
• The location of synthesis is the cytosol, primarily within the liver.
• The enzyme involved is fatty acid synthase.
• Fatty acid synthesis involves growing the fatty acid chain in two-carbon increments.

Overall Regulation of Lipid Metabolism

• Regulation of lipid metabolism varies depending on fasting/exercise and after a meal/resting state.
• During fasting/exercise, hormones like glucagon and epinephrine stimulate lipolysis and beta-oxidation.
• After a meal and resting periods, insulin stimulates fatty acid synthesis.
• Carbohydrate-rich diets can also promote fatty acid synthesis.