Lipid Metabolism: Fatty Acid Utilisation for Energy Production PDF

LIPID METABOLISM UTILIZATION OF FATTY ACIDS FOR ENERGY PRODUCTION  Fatty acid as a fuel in muscle Fatty acid oxidation occurs in mitochondria. Quantitatively muscle is a major consumer of fat. Although carbohydrates and fatty acids may both be used as fuels for muscle contrac...

LIPID METABOLISM UTILIZATION OF FATTY ACIDS FOR ENERGY PRODUCTION  Fatty acid as a fuel in muscle Fatty acid oxidation occurs in mitochondria. Quantitatively muscle is a major consumer of fat. Although carbohydrates and fatty acids may both be used as fuels for muscle contraction, fatty acids are more calorific (energy producing) yielding approximately 38 kJ/mol compared with approximately 16 kJ/mol for glucose. These points can be better appreciated by comparing the complete oxidation of glucose with that of a typical saturated fatty acid, palmitate. With a free energy change sufficient to generate 106 moles of ATP per mole of fatty acid (palmitic acid). However, it should be noted that although fat oxidation provides quantitatively more ATP than does the oxidation of glucose, the rate at which ATP is generated via beta- oxidation is slower than the rate of generation by glycolysis; a fact which explains why glucose is the preferred fuel during sudden bursts of muscular activity when ATP concentration need to be ‘topped-up’ rapidly.  Insulin Glucagon Inhibits HSL Activates HSL via dephosphorylation via phosphorylation In fed state In fasted state  β oxidation β oxidation is the catabolic process by which FA molecules are broken down in the mitochondria in eukaryotes to generate acetyl CoA which enters in the TCA cycle and NADH and FADH2, which are coenzymes used in ETC. It is named as such because the β carbon of the FA undergoes oxidation to a second Carbon (carbonyl carbon). β-oxidation reactions α-Oxidation of fatty acids Branched-chain, 20 carbon fatty acid, phytanic acid: undergoes alpha- oxidation because of the methyl group on its β carbon. Refsum disease is a rare, autosomal recessive disorder. This results in the accumulation of phytanic acid in the plasma and tissues. The symptoms are primarily neurologic, and the treatment involves dietary restriction to halt disease progression. Note: ω-Oxidation (at the methyl terminus) also is known.  Ketone bodies are important sources of energy for the peripheral tissues because 1) they are soluble in aqueous solution. 2) they are produced in the liver during prolonged fasting 3) they are used in proportion to their concentration in the blood by extrahepatic tissues, such as the skeletal and cardiac muscle and renal cortex. Even the brain can use ketone bodies to help meet its energy needs if the blood levels rise sufficiently; Figure 17.24 Structures of ketone bodies. Textbook of Biochemistry with Clinical Correlations, 7e edited by Thomas M. Devlin © 2011 John Wiley & Sons, Inc. Although the liver actively produces ketone bodies, it lacks thiophorase and, therefore, is unable to use ketone bodies as fuel. Excessive production of ketone bodies in diabetes mellitus When the rate of formation of ketone bodies is greater than the rate of their use, their levels begin to rise in the blood (ketonemia) and, eventually, in the urine (ketonuria). This is seen most often in cases of uncontrolled, type 1 diabetes mellitus. A frequent symptom of diabetic ketoacidosis is a fruity odor on the breath, which results from increased production of acetone (spontaneously released from Acetoacetate). [Note: The carboxyl group of a ketone body has a pKa of about 4. Therefore, each ketone body loses a proton (H+) as it circulates in the blood, which lowers the pH of the body. Also, excretion of glucose and ketone bodies in the urine results in dehydration of the body. Therefore, the increased number of H+, circulating in a decreased volume of plasma, can cause severe acidosis (ketoacidosis).] Ketoacidosis may also be seen in cases of fasting