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Metabolism of Lipids and Proteins Chapter 35 Hein and Arena Version 1.0 Colleen Kelley Chemistry Department 1 College Pima Community © John Wiley and Sons, Inc. Chapter Outline 35.1 Metabolic Energy Sources 35.2 Fatty Acid Oxidation (Beta Oxidation) 35.3 Fat Storage and Utilization 35. 4 Biosynthesis of Fatty Acids (Lipogenesis) 35.5 Amino Acid Metabolism 35.6 Metabolic Nitrogen Fixation 35.7 Amino Acids and Metabolic Nitrogen Balance 35.8 Amino Acids and Nitrogen Transfer 35.8 Nitrogen Excretion and the Urea Cycle 35.9 Nitrogen Excretion and the Urea Cycle 35.10 Acetyl-CoA, a Central Molecule in Metabolism 2 Metabolic Energy Sources 3 1) Lipids - fatty acids are used most commonly for cellular energy. - Ex: palmitic acid, CH3(CH2)14COOH 2) Proteins (amino acids) - Source of reduced carbon atoms that can be catabolized to provide cellular energy. - Provide the major pool of usable nitrogen for cells. 4 Fatty Acid Oxidation 5 • Fats are the most energy-rich class of nutrients. • Most of the energy from fats is derived from their constituent fatty acids. 6 • Fats are broken down in a series of enzymecatalyzed reactions that also produce useful potential energy in the form of ATP. • In complete biochemical oxidation, the carbon and hydrogen of a fat ultimately are combined with oxygen (from respiration) to form carbon dioxide and water. 7 Beta Oxidation • Beta oxidation, or the two-carbon chop, is accomplished in a series of reactions whereby the first two carbon atoms of the fatty acid chain become the acetyl group in a molecule of acetyl-CoA. 8 9 Figure 35.1 A comparison of ATPs produced from 18 carbons of one stearic acid molecule and 18 carbons of three glucose 10 molecules. Fat Storage and Utilization 11 • Fats (triacylglycerols) are stored primarily in adipose tissue, which is widely distributed in the body. • Fat is the major reserve of potential energy. 12 Biosynthesis of Fatty Acids (Lipogenesis) 13 • The biosynthesis of fatty acids from acetylCoA is called lipogenesis. • Acetyl-CoA can be obtained from the catabolism of carbohydrates, fats, or proteins. • After they are synthesized, fatty acids combine with glycerol to form triacylglycerols, which are stored in adipose tissue. • Consequently, lipogenesis is the pathway by which all three of the major classes of nutrients are ultimately converted to fat. 14 Lipogenesis vs. Beta Oxidation 1. Fatty acid catabolism occurs in the mitochondria, but fatty acid anabolism (lipogenesis) occurs in the cytoplasm. 2. Lipogenesis requires a set of enzymes that are different from the enzymes used in the catabolism of fats. 15 Lipogenesis vs. Beta Oxidation 3. In the anabolic pathway (lipogenesis), the growing fatty acid chain bonds to a special acyl carrier protein, ACP-SH, which acts as a ‘handle’ to transfer the growing chain from one enzyme to another through the series of enzymecatalyzed reactions in the pathway. Coenzyme A is the carrier in fatty acid catabolism. 16 Lipogenesis vs. Beta Oxidation 4. A preliminary set of reactions, involving malonyl-CoA, occurs for each two-carbon addition cycle in the synthesis. “Malonyl-” refers to a threecarbon group and has no counterpart in the catabolic pathway. 17 Steps in Lipogenesis 18 Amino Acid Metabolism 19 • Amino acids serve an important and unique role in cellular metabolism; they are the building blocks of proteins and also provide most of the nitrogen for other nitrogencontaining compounds. • The metabolism of the carbon structures of amino acids is very complex: – – – – Metabolic nitrogen fixation Nitrogen balance Nitrogen transfer Nitrogen excretion 20 Metabolic Nitrogen Fixation 21 Nitrogen Fixation • The conversion of diatomic nitrogen (N2) to a biochemically useful form is termed nitrogen fixation. 22 Nitrogen Fixation • Atmospheric nitrogen is fixed – that is, converted into chemical compounds that are useful in higher forms of life – by three general routes: 1. Bacterial action 2. High temperature 3. Chemical fixation 23 Nitrogen Cycle The process by which nitrogen is circulated and recirculated from the atmosphere through living organisms and back to the atmosphere is known as the nitrogen cycle. 24 Figure 35.2 The nitrogen cycle. Arrows indicate the movement of nitrogen through the cycle. 25 Amino Acids and Metabolic Nitrogen Balance 26 • • Protein is digested and absorbed to provide the amino acid dietary requirements. Once absorbed, an amino acid can be: 1. Incorporated into a protein 2. Used to synthesize other nitrogenous compounds such as nucleic acids, or 3. Deaminated to a keto acid, which can either be used to synthesize other compounds or be oxidized to carbon dioxide and water to provide energy. 27 Amino Acid Pool • Absorbed amino acids enter the amino acid pool – the total supply of amino acids available for use throughout the body. 28 Figure 35.3 Major biological nitrogen pools related to the central amino acid pool. 29 Nitrogen Balance • Nitrogen balance occurs when the nitrogen pools within the body remain constant. 30 Amino Acids and Nitrogen Transfer 31 Transamination • In general, when an amino acid is used for some purpose other than protein synthesis, the amino acid carbon skeleton is separated from the amino acid nitrogen. • A process called transamination is responsible for most of the nitrogen transfer to and from amino acids. 32 Transamination • Transamination is the transfer of an amino group from an -amino acid to an -keto acid: 33 34 Nitrogen Excretion and the Urea Cycle 35 Figure 35.4 Urea Cycle. The cycle begins with the reaction between carbamoyl phosphate and ornithine. 36 37 Acetyl-CoA, a Central Molecule in Metabolism 38 Figure 35.5 Simplified diagram showing acetyl-CoA is at the hub of protein, carbohydrate and fat metabolism. 39 40