《有机化学》课程PPT教学课件（Organic Chemistry with Biological Applications, 3th Edition, John McMurry, 2016）Chapter 20 Amino Acid Metabolism

CNGNGE JOHN MCMURRY CHAPTER 20 Amino Acid Metabolism Organic Chemistry with Biological Applications

CHAPTER 20 Amino Acid Metabolism

20-1 An Overview of Metabolism and Biochemical Energy Metabolism A collective name for the many reactions that go on in the cells of living organisms Catabolism The group of metabolic pathways that break down larger molecules into smaller ones Pathways are often exergonic and release energy Anabolism The group of metabolic pathways that build up larger molecules from smaller ones Pathways are often endergonic and absorb energy

Metabolism ▪ A collective name for the many reactions that go on in the cells of living organisms ▪ Catabolism ▪ The group of metabolic pathways that break down larger molecules into smaller ones ▪ Pathways are often exergonic and release energy ▪ Anabolism ▪ The group of metabolic pathways that build up larger molecules from smaller ones ▪ Pathways are often endergonic and absorb energy 20-1 An Overview of Metabolism and Biochemical Energy

An Overview of Metabolism and Biochemical Energy Fats Carbohydrates Proteins Catabolic pathways Stage 1 Bulk food is hydrolyzed in the for the degradation stomach and small intestine Hydrolysis Hydrolysis Hydrolysis to give small molecules. of food and the Fatty acids, Glucose,fructose,other Amino acids glycerol monosaccharides production of biochemical energy Stage 2 Fatty acids,monosaccharides and amino acids are degraded in cells to yield acetyl CoA. Stage 3 Acetyl CoA is oxidized in the citric acid cycle to give CO2. Citrie acid cycle Stage 4 The energy released in the Electron citric acid cycle is used by the transport electron-transport chain to chain oxidatively phosphorylate ADP and produce ATP ATP H2O

Catabolic pathways for the degradation of food and the production of biochemical energy An Overview of Metabolism and Biochemical Energy

An Overview of Metabolism and Biochemical Energy Catabolic stages: Stage 1 Food is digested by hydrolysis of ester,glycoside (acetal), and peptide (amide)bonds to yield primarily fatty acids plus glycerol,simple sugars,and amino acids Stage 2 Molecules are further degraded in the cytoplasm of the cells to yield acetyl groups attached by a thioester bond to the large carrier molecule coenzyme A The resultant compound,acetyl coenzyme A (acetyl CoA),is a key substance in the metabolism of food molecules and in numerous other biological pathways

Catabolic stages: Stage 1 ▪ Food is digested by hydrolysis of ester, glycoside (acetal), and peptide (amide) bonds to yield primarily fatty acids plus glycerol, simple sugars, and amino acids Stage 2 ▪ Molecules are further degraded in the cytoplasm of the cells to yield acetyl groups attached by a thioester bond to the large carrier molecule coenzyme A ▪ The resultant compound, acetyl coenzyme A (acetyl CoA), is a key substance in the metabolism of food molecules and in numerous other biological pathways An Overview of Metabolism and Biochemical Energy

An Overview of Metabolism and Biochemical Energy -The acetyl group in acetyl CoA is linked to the sulfur atom of phosphopantetheine,which is itself linked to adenosine 3',5'-bisphosphate CH3 O CH3C-SCH2CH2NHCCH2CH2NHCCHCCH2OP-OPOCH2 HO CH3 0 0 Phosphopantetheine 203P0 OH Adenosine 3',5'-bisphosphate Acetyl CoA-a thioester

▪ The acetyl group in acetyl CoA is linked to the sulfur atom of phosphopantetheine, which is itself linked to adenosine 3’,5’-bisphosphate An Overview of Metabolism and Biochemical Energy

An Overview of Metabolism and Biochemical Energy Stage 3 Citric acid cycle Acetyl groups are oxidized inside cellular mitochondria to yield CO2 This stage releases a large amount of energy Stage 4 The electron transport chain Energy made in the citric acid cycle used during the fourth stage,the electron-transport chain,to accomplish the endergonic phosphorylation of ADP with hydrogen phosphate ion(HOPO32-,abbreviated Pi)to give ATP

Stage 3 Citric acid cycle ▪ Acetyl groups are oxidized inside cellular mitochondria to yield CO2 ▪ This stage releases a large amount of energy Stage 4 The electron transport chain ▪ Energy made in the citric acid cycle used during the fourth stage, the electron-transport chain, to accomplish the endergonic phosphorylation of ADP with hydrogen phosphate ion (HOPO3 2- , abbreviated Pi) to give ATP An Overview of Metabolism and Biochemical Energy

An Overview of Metabolism and Biochemical Energy ATP,the final result of food catabolism,has been called the 'energy currency"of the cell Energy production and use in living organisms revolve around the ATPs ADP interconversion Catabolic reactions "buy"ATP with energy released by synthesizing it from ADP plus hydrogen phosphate ion Anabolic reactions "spend"ATP by transferring a phosphate group to another molecule,thereby regenerating ADP NH2 NH2 Diphosphate Triphosphate HOPO32,H* CH2 -H20 OH OH OHOH Adenosine diphosphate(ADP) Adenosine triphosphate(ATP) Cangage Learing.All Rights Resarved

ATP, the final result of food catabolism, has been called the “energy currency” of the cell ▪ Energy production and use in living organisms revolve around the ATP ⇆ ADP interconversion ▪ Catabolic reactions “buy” ATP with energy released by synthesizing it from ADP plus hydrogen phosphate ion ▪ Anabolic reactions “spend” ATP by transferring a phosphate group to another molecule, thereby regenerating ADP An Overview of Metabolism and Biochemical Energy

An Overview of Metabolism and Biochemical Energy ADP and ATP are phosphoric acid anhydrides O a Contain linkage in carboxylic acid anhydrides React with alcohols by breaking a P-O bond and forming a phosphate ester,ROPO32-.The reaction is a nucleophilic acyl substitution at phosphorus Phosphorylation reactions with ATP require the presence of divalent metal cation in the enzyme,usually Mg2+,to form a Lewis acid-base complex with the phosphate oxygen atoms and neutralize some negative charge H 0 Adenosine Adenosine ATP Mg2+ 00 B-O-P-0+ OPOP-O-Adenosine +Mg2+ A phosphate ester ADP

ADP and ATP are phosphoric acid anhydrides ▪ Contain linkages analogous to the linkage in carboxylic acid anhydrides ▪ React with alcohols by breaking a P-O bond and forming a phosphate ester, ROPO3 2- . The reaction is a nucleophilic acyl substitution at phosphorus ▪ Phosphorylation reactions with ATP require the presence of divalent metal cation in the enzyme, usually Mg2+,to form a Lewis acid-base complex with the phosphate oxygen atoms and neutralize some negative charge An Overview of Metabolism and Biochemical Energy

An Overview of Metabolism and Biochemical Energy An energetically unfavorable reaction "couples"with an energetically favorable reaction so that the overall free- energy change for the two reactions together is favorable Coupled reactions Imagine that reaction 1 does not occur to any reasonable extent because it has a small equilibrium constant and is energetically unfavorable,the reaction has AG 0 (1)A+m二B+n△G>0 where A and B are the biochemically "interesting"substances undergoing transformation,while m and n are enzyme cofactors, H2O,or other substances

An energetically unfavorable reaction “couples” with an energetically favorable reaction so that the overall free￾energy change for the two reactions together is favorable Coupled reactions ▪ Imagine that reaction 1 does not occur to any reasonable extent because it has a small equilibrium constant and is energetically unfavorable, the reaction has ∆G > 0 (1) A + m B + n ∆G > 0 where A and B are the biochemically “interesting” substances undergoing transformation, while m and n are enzyme cofactors, H2O, or other substances An Overview of Metabolism and Biochemical Energy

An Overview of Metabolism and Biochemical Energy Imagine that the product n can react with substance o to yield p and q in a second,strongly favorable reaction that has a large equilibrium constant and△G0 (2)H+0一→p+q △G<<0 Net:A+m+0-→B+p+q △G<0 企Laeri'g月ha

Imagine that the product n can react with substance o to yield p and q in a second, strongly favorable reaction that has a large equilibrium constant and ∆G << 0: (2) n + o p + q ∆G << 0 Because the two reactions are coupled through n, the transformation of A to B becomes possible ▪ When an amount of n is formed in reaction 1, it undergoes a complete conversion in reaction 2, thereby removing it from the first equilibrium and forcing reaction 1 to continually replenish n until the reactant A is gone ▪ The two reactions added together have a favorable ∆G < 0 ▪ The favorable reaction 2 “drives” the unfavorable reaction 1 An Overview of Metabolism and Biochemical Energy