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CHAPTER 24: Carbohydrate, Lipid, & Protein Metabolism General, Organic, & Biological Chemistry Janice Gorzynski Smith CHAPTER 24: Carbohydrate, Lipid, & Protein Metabolism Learning Objectives: Role in Metabolism of fatty acid oxidation, glycolysis, & Amino acid catabolism Reactions catalyzed by: kinase, isomerase, dehydrogenase, decarboxylase, carboxylase Glycolysis: steps & net reaction Pyruvate conversion to acetyl Coenzyme A Gluconeogenesis: steps in synthesis of glucose Catabolism of Triacylglycerols: beta-oxidation Synthesis of ketone bodies: ketogenesis Catabolism of Amino acids: transamination & oxidative deamination Ketogenic vs glucogenic amino acid catabolism CH 24 Homework: End of Chapter problems: 30, 36, 38, 42, 47, 52, 58, 60, 64, 68, 71, 75, 76, 78, 80, 82, 96, 98 Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 2 Metabolism Step 2 of Metabolism • Fatty acid oxidation • Glycolysis • Amino Acid Catabolism All lead to the production of Acetyl CoA Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 3 Metabolism Step 2 of Metabolism •In the catabolism of carbohydrates, glycolysis converts glucose into pyruvate, which is then metabolized into acetyl CoA. Metabolism Step 2 of Metabolism •In the catabolism of lipids, fatty acids are converted into thioesters and then cleaved into many acetyl CoA units. Metabolism Step 2 of Metabolism •Amino acids are usually reassembled into new proteins. •Since excess amino acids are not stored in the body, they can also be catabolized for energy. •The amino groups (NH2) are converted to urea [(NH2)2C=O], which is excreted in urine. Metabolism Step 2 of Metabolism: Urea Cycle http://www.t3portal.org/T3_Portal_v1/!SSL!/WebHelp/ales_vancura Catabolism_of_amino_acids.htm Biochemical Rxns Common Enzymes Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 8 Biochemical Rxns Common Enzymes: Example •The transfer of a phosphate unit from ATP to the fructose 6-phosphate molecule is catalyzed by a kinase enzyme. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 9 Glycolysis Definition •Glycolysis is a linear, 10-step anaerobic pathway that converts glucose into two molecules of pyruvate. •Steps [1] – [5] comprise the energy investment phase, where 2 ATP molecules are hydrolyzed. •The 6-carbon glucose molecule is converted into two 3-carbon segments. •Steps [6] – [10] comprise the energygenerating phase, producing 1 NADH and 2 ATPs for each pyruvate formed. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 10 Glycolysis Energy Investment Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 11 Glycolysis Energy Generation Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 12 Glycolysis Step 1 •Step [1] begins with the phosphorylation of glucose into glucose 6-phosphate, using an ATP and a kinase enzyme. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 13 Glycolysis Step 2 •Step [2] isomerizes glucose 6-phosphate to fructose 6-phosphate with an isomerase enzyme. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 14 Glycolysis Step 3 •Step [3] is the phosphorylation of fructose 6-phosphate into fructose 1,6-bisphosphate with a kinase enzyme. Steps [1-3] add 2 phosphate groups and isomerize a 6membered ring into a 5membered ring. Energy is stored as 2 ATP molecules. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 15 Glycolysis Step 4 •Step [4] cleaves the fructose ring into a dihydroxyacetone phosphate and a glyceraldehyde 3-phosphate. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 16 Glycolysis Step 5 •Step [5] isomerizes the dihydroxyacetone phosphate into another glyceraldehyde 3-phosphate. •Thus, the first phase of glycolysis converts glucose into 2 glyceraldehyde 3-phosphate units. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 17 Glycolysis Step 6 •In step [6] the aldehyde end of the molecule is oxidized and phosphorylated by a dehydrogenase enzyme and NAD+; this produces 1,3-bisphosphoglycerate and NADH. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 18 Glycolysis Step 7 •In step [7], the phosphate group is transferred onto an ADP with a kinase enzyme, forming 3-phosphoglycerate and ATP. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 19 Glycolysis Step 8 •In step [8], the phosphate group is isomerized to a new position in 2-phosphoglycerate. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 20 Glycolysis Step 9 •In step [9], water is lost to form phosphoenolpyruvate. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 21 Glycolysis Step 10 •In step [10], the phosphate is transferred to an ADP, yielding pyruvate and ATP with a kinase enzyme. •The 2 glyceraldehyde 3-phosphate units are converted into 2 pyruvate units in Phase two of glycolysis. •Overall, the energy-generating phase forms 2 NADHs and 4 ATPs. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 22 Glycolysis Overall Reaction •2 ATPs are used in phase one of glycolysis, and 4 ATPs are made in phase two of glycolysis. •The net result is the synthesis of 2 ATPs from glycolysis •The 2 NADHs formed are made in the cytoplasm and must be transported to the mitochondria to join the electron transport chain and make ATP. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 23 Glycolysis Pyruvate Pyruvate can be converted into three possible products depending on the conditions and the organism. under aerobic conditions under anaerobic conditions Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. in fermentation by microorganisms 24 Glycolysis Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. ATP Yield 25 Glycolysis ATP Yield 2 x 2.5 ATP = 5 ATP 2 x 2.5 ATP = 5 ATP 2 ATP Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 6 x 2.5 = 15 ATP 2 x 1.5 = 26 3 ATP Gluconeogenesis Definition •Gluconeogenesis is the synthesis of glucose from noncarbohydrate sources—lactate, amino acids, or glycerol. •Gluconeogenesis is an anabolic pathway since it results in the synthesis of larger molecules from smaller ones. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 27 Gluconeogenesis Cori Cycle Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 28