Fatty Acid Catabolism - Biochemistry II PDF

CHAPTER 6 FATTY ACID CATABOLISM BIOCHEMISTRY II Tell: 087380160  CONTENTS I. Introduction to Fatty acid II. Digestion, mobilization, and transport of fats III. Oxidation of fatty acids IV. Ketone bodies  INTRODUCTION TO FATTY ACID...

CHAPTER 6 FATTY ACID CATABOLISM BIOCHEMISTRY II Tell: 087380160  CONTENTS I. Introduction to Fatty acid II. Digestion, mobilization, and transport of fats III. Oxidation of fatty acids IV. Ketone bodies  INTRODUCTION TO FATTY ACID Fats Fats are part of many body tissues and are important as carriers of other nutrients, such as vitamins. Fats also carry the flavor of foods – making foods tastier, but consumption of fat should be closely monitored. Metabolism of Fatty acid Lipid is a component of cell membrane  INTRODUCTION TO FATTY ACID 4 Fats are a type of lipid, which is a broad category of hydrophobic molecules that includes not just fats but also oils, waxes, phospholipids, and steroids. Fats in Diet and Function Energy Storage: Fats are a concentrated source of energy, providing 9 kcal per gram. Insulation and Protection: Fat stores cushion organs and insulate the body. Essential Fatty Acids: Certain fats like omega-3 and omega-6 fatty acids are vital for health. Vitamin Absorption: Fats are necessary for the absorption of fat-soluble vitamins (A, D, E, K). INTRODUCTION TO FATTY ACID 5 Source of fat or oil INTRODUCTION TO FATTY ACID 6 Fats Fatty acids  INTRODUCTION TO FATTY ACID 7 Fatty acids are a fundamental class of organic compounds that serve as key building blocks of lipids in biological systems. They play critical roles in energy storage, cell membrane structure, and signaling processes. Basic Structure: Fatty acids consist of a hydrocarbon chain with a terminal carboxylic acid group (-COOH). The hydrocarbon chain can vary in length and saturation. General Formula: 𝐶𝐻3−(𝐶𝐻2)𝑛−𝐶𝑂𝑂𝐻CH 3 −(CH 2 ) n −COOH  INTRODUCTION TO FATTY ACID 8 Classification of Fatty acid:  INTRODUCTION TO FATTY ACID 9 Structure of Saturate and unsaturated Fatty acid: INTRODUCTION TO FATTY ACID 10 DIGESTION, MOBILIZATION, AND TRANSPORT OF FATS 11 DIGESTION, MOBILIZATION, AND TRANSPORT OF FATS 12 DIGESTION, MOBILIZATION, AND TRANSPORT OF FATS 13 Structure: Composed of large fat-storing cells called adipocytes, with a single lipid droplet dominating the cell. 14 DIGESTION, MOBILIZATION, AND TRANSPORT OF FATS Stomach Pancreatic juices Stimulate Intestine CCK Intestine cells Lipase and the hydrolysis of Stimulate triacylglycerol. Bile salt Fats absorption DIGESTION, MOBILIZATION, AND TRANSPORT OF FATS 16  17 Hormones play a pivotal role in the mobilization of stored triacylglycerols (TAGs), particularly during periods of energy demand such as fasting, exercise, or stress. This process ensures the release of fatty acids and glycerol for energy production. 1. Epinephrine (Adrenaline): Secreted during stress or physical activity, signaling the need for rapid energy mobilization. 2. Glucagon: Released during fasting or low blood glucose levels to promote energy availability. 3. Insulin (inhibitory): Released postprandially (after meals) to inhibit lipolysis and promote TAG storage.  Mechanism of TAG Mobilization 18 TAG mobilization is a tightly regulated biochemical process that occurs predominantly in adipocytes to provide energy during fasting, exercise, or stress. Below is a step-by-step explanation of the mechanism: TAG → (ATGL) → DAG → (HSL) → MAG → (MAGL) → Glycerol + FFAs Step 1 1. Hormonal Signal Activation Triggering Hormones: Epinephrine (adrenaline): Released during stress or exercise. Glucagon: Released during fasting or low blood glucose. Receptor Binding: Hormones bind to their respective receptors on adipocyte membranes: β-adrenergic receptors for epinephrine. Glucagon receptors for glucagon. Step 2 19 2. Activation of Adenylyl Cyclase The hormone-receptor interaction activates a G-protein (specifically the Gs protein). The Gs protein stimulates adenylyl cyclase, an enzyme on the inner surface of the cell membrane. Adenylyl cyclase converts ATP to cyclic AMP (cAMP). Step 3 3. Activation of Protein Kinase A (PKA) cAMP serves as a second messenger, activating protein kinase A (PKA). PKA phosphorylates target proteins to initiate lipolysis: Hormone-sensitive lipase (HSL). Perilipin, a protein that coats lipid droplets.  20 Step 4 4. Lipolysis Initiation 1.Perilipin Phosphorylation: 1. Phosphorylated perilipin restructures the lipid droplet, exposing TAGs to lipases. 2.Activation of Lipases: 1. Adipose triglyceride lipase (ATGL): 1. Hydrolyzes TAGs into diacylglycerols (DAGs) and one free fatty acid (FFA). 2. Hormone-sensitive lipase (HSL): 1. Hydrolyzes DAGs into monoacylglycerols (MAGs) and another FFA. 3. Monoacylglycerol lipase (MAGL): 1. Converts MAGs into glycerol and the final FFA.  21 Step 5 5. Release of Products Free Fatty Acids (FFAs): Released into the bloodstream and transported by binding to albumin. Taken up by tissues like muscle and liver for β-oxidation and ATP production. Glycerol: Enters the bloodstream and is transported to the liver. In the liver, it is used in gluconeogenesis or glycolysis. 22 23 24 25 26 CONTINUE…  IV. Oxidation of fatty acids 28 Fatty acid oxidation is initiated on the outer mitochondrial membrane. There the fatty acids, which like carbohydrates are relatively inert, must first be activated by conversion to an energy-rich fatty acid derivative of coenzyme A called fatty acyl-coenzyme A (CoA). The activation is catalyzed by acyl-CoA synthetase. For each molecule of fatty acid activated, one molecule of coenzyme A and one molecule of adenosine triphosphate (ATP) are used, equaling a net utilization of the two high-energy bonds in one ATP molecule (which is therefore converted to adenosine monophosphate [AMP] rather than adenosine diphosphate [ADP]).  IV. Oxidation of fatty acids 29 The fatty acyl-CoA diffuses to the inner mitochondrial membrane, where it combines with a carrier molecule known as carnitine in a reaction catalyzed by carnitine acyltransferase. The acyl-carnitine derivative is transported into the mitochondrial matrix and converted back to the fatty acyl-CoA. Carnitine is an amino acid derivative synthesized from methionine and lysine.  IV. Oxidation of fatty acids 30 Steps in the β-Oxidation of Fatty Acids Further oxidation of the fatty acyl-CoA occurs in the mitochondrial matrix via a sequence of four reactions known collectively as β-oxidation because the β-carbon undergoes successive oxidations in the progressive removal of two carbon atoms from the carboxyl end of the fatty acyl-CoA. IV. Oxidation of fatty acids 31 IV. Oxidation of fatty acids 32 IV. Oxidation of fatty acids 33 IV. Oxidation of fatty acids 34 IV. Oxidation of fatty acids 35 V. Ketone bodies 36 Ketone bodies are substances produced by the liver during gluconeogenesis, a process that creates glucose in times of fasting and starvation. There are three ketone bodies produced by the liver. They are acetoacetate, beta-hydroxybutyrate, and acetone. These compounds are used in healthy individuals to provide energy to the cells of the body when glucose is low or absent in the diet.  V. Ketone bodies 37 The liver, in order to keep supplying the brain with glucose, must convert amino acids, glycerol, pyruvate, and lactate into glucose. This process is called gluconeogenesis, and also produces the two ketone bodies acetoacetate and beta-hydroxybutyrate. Formation of ketone bodies V. Ketone bodies 38 How Ketone bodies are produce 39 Fasting, exercise, starvation, diabetic type 1 Low blood glucose, then glycogenosis occurs, Fatty acid are resort for energy ▪ The brain prefers glucose as a source of energy but will begin to switch to ketone bodies after about 4 days of starvation. This greatly increases the amount of time an organism can go without food, however it can also begin to cause negative side- Fatty acid breakdown effects. into ketone bodies ▪ If food is not eaten to replenish the glucose supply, ketone bodies can begin to build up. While ketone bodies are removed Transport to liver and by your kidneys, if they are produced at a high rate they can convert to Acetyl-coA overwhelm the kidney. Acetyl co-A enters Krebs cycle  V. Ketone bodies 40 Keto Diet ❑ These diets focus on low carbohydrates and high protein. Because carbohydrates are complex forms of glucose, removing them from the diet effectively removes glucose from the diet. ❑ Low-carbohydrate, high-protein diets can mimic starvation, leading the body to rely on fat for energy. This triggers gluconeogenesis in the liver to supply glucose for the brain and produces ketone bodies. Over time, declining glucose levels reduce intermediates needed to utilize ketone bodies, causing their accumulation. The kidneys attempt to remove excess ketone bodies, but their capacity is limited, increasing the risk of ketoacidosis. V. Ketone bodies 41 Diabetes is a condition where the body cannot produce or respond to insulin, a hormone that signals cells to absorb glucose for energy. Without insulin, glucose remains in the blood, leading to high blood sugar levels. In response, the body switches to using fatty acids for energy. In diabetes, the liver compensates for the lack of glucose in cells. diabetics lack the necessary intermediaries, typically derived from glucose breakdown, but utilize ketone bodies for energy. This leads to a rapid buildup of ketone bodies in the blood and cause acidosis. https://biologydictionary.net/ketone-bodies/ https://chem.libretexts.org/Courses/Brevard_College/CHE_3 01_Biochemistry/09%3A_Metabolism_of_Lipids/9.04%3A_O xidation_of_Fatty_Acids