Fatty acid synthesis is a biochemical pathway responsible for making fatty acids from excess carbohydrates. Fatty acids primarily serve as the main storage of energy and are essential components in constructing cell membranes and lipoproteins. Key components in this process include acetyl-CoA, malonyl-CoA, insulin, and fatty acid synthase (FAS). Synthesis takes place in the cytosol of adipose tissue, hepatocytes, and lactating mammary glands when there are high levels of glucose and ATP available inside cells.
To begin the synthesis, acetyl-CoA must combine with oxaloacetate to form citrate. This citrate then crosses the mitochondrial membrane and enters the cytosol where it is converted back to acetyl-CoA and oxaloacetate by ATP citrate lyase. The enzyme acetyl-CoA carboxylase irreversibly uses ATP to add a CO2 group to acetyl-CoA, forming malonyl-CoA. Insulin and citrate activate acetyl-CoA carboxylase, while glucagon, epinephrine, and palmitoyl-CoA inhibit it. Finally, fatty acid synthase produces the 16-carbon palmitic acid from acetyl-CoA and malonyl-CoA, which can undergo further modifications in the smooth endoplasmic reticulum.
<ul> <li>Fats are important for various functions such as phospholipids, lipoproteins, and breastmilk.</li> <li>Main role of fats: energy storage.</li> <li>Fatty acid synthesis: biochemical pathway making fatty acids from excess carbohydrates.</li> <li>Types of fats: <ul> <li>Saturated fats</li> <li>Unsaturated fats</li> </ul> </li> <li>Essential fatty acids: <ul> <li>Omega 3 fats (ALA, EPA, DHA)</li> <li>Omega 6 fat (linoleic acid)</li> </ul> </li> <li>Fatty acids are stored as triglycerides in adipose tissue.</li> <li>Fatty acid synthesis location: cytosol of adipose tissue, hepatocytes, and lactating mammary glands.</li> <li>Conditions for fatty acid synthesis: excess glucose and ATP inside cells, insulin release.</li> <li>Process of fatty acid synthesis: <ul> <li>Glycolysis to make pyruvate</li> <li>Pyruvate enters mitochondrial matrix and becomes acetyl-CoA</li> <li>Acetyl-CoA enters TCA cycle</li> <li>ATP slows down TCA cycle, leading to excess acetyl-CoA</li> </ul> </li> <li>Transport of acetyl-CoA out of mitochondria: <ul> <li>Acetyl-CoA cannot cross the membrane alone</li> <li>Citrate synthase makes citrate from acetyl-CoA and oxaloacetate</li> <li>Citrate crosses the membrane</li> <li>Citrate converted back to acetyl-CoA by ATP citrate lyase</li> </ul> </li> <li>Oxaloacetate transport: <ul> <li>Oxaloacetate in the cytosol is reduced to malate, which can be transported into the mitochondria and converted back to oxaloacetate.</li> <li>Note: this process produces NADPH, which is needed for fatty acid synthesis</li> </ul> </li> <li>Acetyl-CoA carboxylase: <ul> <li>Uses ATP to add a CO2 group to acetyl-CoA, making malonyl-CoA</li> <li>Requires vitamin B7 (biotin)</li> <li>Regulation by insulin, citrate, glucagon, epinephrine, and palmitoyl-CoA</li> </ul> </li> <li>Fatty acid synthase (FAS): <ul> <li>Large multi-enzyme complex responsible for making palmitic acid</li> <li>Initiation: binding of acetyl-CoA and malonyl-CoA to FAS</li> <li>Series of 4 reactions to add 2 carbons each cycle and grow fatty acyl CoA</li> <li>Final product: 16-carbon palmitic acid</li> </ul> </> <li>Palmitic acid modifications in the smooth ER: <ul> <li>Converted to palmitoyl-CoA</li> <li>Desaturases add double bonds</li> </ul> </li> </ul>
Fatty acid synthesis is crucial for the production of phospholipids, which are a primary component of cell membranes. Phospholipids consist of a hydrophilic head containing a phosphate group and two hydrophobic tails derived from fatty acids. The fatty acids can be either saturated or unsaturated, affecting the fluidity and function of cell membranes. Fatty acid synthesis provides the building blocks necessary to create these essential components in cells.
Saturated fats contain only single bonds between their carbon atoms, leading to a straight and compact structure. Unsaturated fats contain at least one double bond between carbon atoms, which creates a kinked structure. This structural difference affects the fluidity and properties of cell membranes. In fatty acid synthesis, the enzyme stearoyl-CoA desaturase introduces double bonds into the fatty acid chain, creating unsaturated fats. Unsaturated fats, such as omega-3 and omega-6 fats, help to regulate important functions, including inflammation, blood clotting, and cholesterol levels.
Omega-3 and omega-6 fats are polyunsaturated fatty acids (PUFAs) that are essential for our health. The body cannot synthesize these fats, so they must be obtained through dietary intake. Omega-3 fats, such as alpha-linolenic acid (ALA), are primarily found in fatty fish, nuts, and seeds. Omega-6 fats, like linoleic acid, are typically found in vegetable oils and seeds. These fatty acids play integral roles in cell membrane structure, inflammation regulation, mood, and cognitive function. An appropriate balance between omega-3 and omega-6 fats is needed to maintain optimal health.
Triglycerides are the primary storage form of fat in the body and are generated through the process of fatty acid synthesis. They consist of a glycerol backbone joined to three fatty acid molecules through ester bonds. Fatty acid synthesis generates the necessary fatty acids that make up triglycerides. Once synthesized, triglycerides can be stored in adipose tissue for later use as an energy source, or they can be incorporated into lipoprotein particles for transport and metabolism.
Adipose tissue, or fat tissue, is composed of adipocytes, which are specialized cells that store lipids in the form of triglycerides synthesized from fatty acids. Adipose tissue plays a crucial role in energy metabolism because it stores excess energy from consumed food in the form of lipids. During periods of fasting or increased energy demand, triglycerides are broken down into fatty acids and glycerol by lipolysis, releasing energy for use by other cells. In addition to energy storage, adipose tissue maintains lipid homeostasis, provides insulation, and produces hormones that regulate energy balance, appetite, and inflammation.