Lecture 8 Metabolism PDF

Lesson 8 Metabolic Pathways and Energy Production 1 Metabolism Metabolism - all chemical reactions that take place in cells to break down (catabolism) or build (anabolism) molecules Metabolic Pathway - A metabolic pathway is a series of linked reactions, each catalyzed...

Lesson 8 Metabolic Pathways and Energy Production 1 Metabolism Metabolism - all chemical reactions that take place in cells to break down (catabolism) or build (anabolism) molecules Metabolic Pathway - A metabolic pathway is a series of linked reactions, each catalyzed by a specific enzyme. - produce energy and cellular compounds. - Such pathways may be linear, in which a series of reactions generates a final product, or cyclic, in which a series of reactions regenerates the first reactant. Metabolism ▪ When we eat food, the polysaccharides, lipids, and proteins are digested to smaller molecules that can be absorbed into the cells of our body. As the glucose, fatty acids, and amino acids are broken down further, energy is released. ▪ Because we do not use all the energy from our foods at one time, we store energy in the cells as high-energy adenosine triphosphate, ATP. -- later broken down obtain energy to do work in our bodies: - contracting muscles - synthesizing large molecules, - sending nerve impulses - moving substances across cell membranes. Metabolism and ATP Energy Metabolism involves: Catabolic reactions that break down large, complex molecules to provide energy and smaller molecules. Anabolic reactions that use ATP energy to build larger molecules. Metabolism and ATP Energy Stages of Metabolism Catabolic reactions are organized as Stage 1: Digestion and hydrolysis break down large molecules to smaller ones that enter the bloodstream. Stage 2: Degradation breaks down molecules to two- and three-carbon compounds. Stage 3: Oxidation of small molecules in the citric acid cycle and electron transport provide ATP energy (electrons are carried by NADH and FADH2) (As long as the cells have oxygen, the hydrogen ions and electrons from the reduced coenzymes are transferred to electron transport to synthesize ATP.) Metabolism and ATP Energy 8 Metabolism and Cell Structure Metabolic reactions occur in specific sites within cells. An organelle is a minute structure within the cytoplasm of a cell that carries out a specific cellular function. The organelles are surrounded by the cytosol, the water-based fluid part of the cytoplasm of a cell. 9.1 Metabolism and ATP Energy Mitochondria are sausage-shaped organelles containing both an: outer membrane: about 50% lipid and 50% protein, is freely permeable to small molecules. Multi-folded inner membrane: about 20% lipid and 80% protein, is highly impermeable to most substances. The nonpermeable nature of the inner membrane divides a mitochondrion into two separate compartments—an interior region called the matrix and the region between the inner and outer membranes, called the intermembrane space. The folds of the inner membrane that protrude into the matrix are called cristae. Important Nucleotide-Containing Compounds in Metabolic Pathways Adenosine triphosphate (ATP) ▪ Is the energy form stored in cells. ▪ Is obtained from the oxidation of food. ▪ Consists of adenine (nitrogen base), a ribose sugar, and three phosphate groups. ▪ Requires 7.3 kcal/mol (or 31 kJ/mol) to convert ADP + Pi to ATP.  13 +7.3 kcal/mol or 31 kJ/mol per bond Important Nucleotide-Containing Compounds in Metabolic Pathways Hydrolysis of ATP ▪ The hydrolysis of ATP to ADP releases 7.3 kcal (31 kJ)/mole. ATP → ADP + Pi + 7.3 kcal/mol (31 kJ/mol) ▪ The hydrolysis of ADP to AMP releases 7.3 kcal (31 kJ)/mole. ADP → AMP + Pi + 7.3 kcal/mol (31 kJ/mol) low energy bond The phosphoanhydride bonds in ATP and ADP are very reactive bonds that require less energy than normal to break. The presence of such reactive bonds, which are often called strained bonds, is the basis for the net energy production that accompanies hydrolysis. Greater-than-normal electron–electron repulsive forces at specific locations within a molecule are the cause for bond strain high energy bond Pi = HPO42- (the form in which phosphate ion exists in solution at physiological pH) 16 Learning Check Match the following: A) ATP B) ADP + Pi 1. Used in anabolic reactions. 2. The energy-storage molecule. 3. Coupled with energy-requiring reactions. 4. Hydrolysis products. 19 Solution Match the following: A) ATP B) ADP + Pi 1. A Used in anabolic reactions 2. A The energy-storage molecule. 3. A Coupled with energy-requiring reactions. 4. B Hydrolysis products. 20 Important Nucleotide-Containing Compounds in Metabolic Pathways Coenzymes in Metabolic Pathways ▪ Several metabolic reactions that extract energy from our food involve oxidation and reduction reactions. ▪ In chemistry, oxidation is often associated with the loss of H atoms, whereas reduction is associated with the gain of H atoms. Often, we represent two H atoms as two hydrogen ions (2H+) and two electrons (2 e̶ ). ▪ In both oxidation and reduction, coenzymes are required to carry the hydrogen ions and electrons from or to the reacting substrate. 21 22 A. Coenzyme NAD+ NAD+ (nicotinamide adenine dinucleotide) ▪ Participates in reactions that produce a carbon-oxygen double bond (C=O) ▪ Is reduced when an oxidation provides 2H+ and 2e-. Oxidation O || CH3—CH2—OH CH3—C—H + 2H+ + 2e- Reduction NAD+ + 2H+ + 2e- NADH + H+ 23 Structure of Coenzyme NAD+ NAD+ ▪ Contains ADP, ribose, and nicotinamide. ▪ Reduces to NADH when the nicotinamide group accepts H+ and 2e-. Copyright © 2007 by Pearson Education, Inc. 24 Publishing as Benjamin Cummings B. Coenzyme FAD FAD (flavin adenine dinucleotide) ▪ Participates in reactions that produce a carbon-carbon double bond (C=C). ▪ Is reduced to FADH2. Oxidation —CH2—CH2— —CH=CH— + 2H+ + 2e- Reduction FAD + 2H+ + 2e- FADH2 25 Structure of Coenzyme FAD ▪ Contains ADP and riboflavin (vitamin B2). ▪ undergoes reduction when the 2 nitrogens in the flavin part react with two hydrogen atoms (2H+ + 2e-) 26 C. Coenzyme A ▪ Consists of aminoethanethiol, pantothenic acid (vitamin B5), phosphorylated ADP (structure in next slide) ▪ Activates acyl groups such as the two-carbon acetyl group for transfer. The reactive feature of coenzyme A is the thiol group (-SH), which bonds to a two-carbon acetyl group to produce the energy-rich thioester acetyl CoA. 27 Structure of Coenzyme A Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 28 Learning Check Match the following: A) NAD+ B) FAD C) NADH + H+ D) FADH2 E) Coenzyme A 1. Coenzyme used in oxidation of carbon-oxygen bonds. 2. Reduced form of flavin adenine dinucleotide. 3. Used to transfer acetyl groups. 4. Contains riboflavin. 5. The coenzyme after C=O bond formation. 29 Solution Match the following: A) NAD+ B) FAD C) NADH + H+ D) FADH2 E) Coenzyme A 1. A Coenzyme used in oxidation of carbon-oxygen bonds. 2. D Reduced form of flavin adenine dinucleotide. 3. E Used to transfer acetyl groups. 4. B,D Contains riboflavin. 5. C The coenzyme after C=O bond formation. 30 High-Energy Phosphate Compounds Several phosphate-containing compounds found in metabolic pathways are known as high-energy compounds. A high-energy compound is a compound that has a greater free energy of hydrolysis than that of a typical compound. High-energy compounds differ from other compounds in that they contain one or more very reactive bonds, often called strained bonds. In a chemical reaction, the energy balance between bond breaking among reactants (energy input) and new bond formation among products (energy release) determines whether there is a net loss or a net gain of energy.  Digestion of Carbohydrates Glycolysis: Oxidation of Glucose Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 33 34 Stage 1: Digestion of Carbohydrates In Stage 1, the digestion of carbohydrates ▪ Begins in the mouth where salivary amylase breaks down polysaccharides to smaller polysaccharides (dextrins), maltose, and some glucose. ▪ Continues in the small intestine where pancreatic amylase hydrolyzes dextrins to maltose and glucose. ▪ Hydrolyzes maltose, lactose, and sucrose to monosaccharides, mostly glucose, which enter the bloodstream for transport to the cells. 35  enzymes produced in the mucosal cells that line the small intestine hydrolyze maltose as well as lactose and sucrose. The bloodstream carries the monosaccharides to the liver, where fructose and galactose are 36 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings converted to glucose. Stage 2: Glycolysis Stage 2: Glycolysis ▪ Is a metabolic pathway that uses glucose, a digestion product. ▪ Degrades glucose (6C) molecules to pyruvate (3C) molecules. ▪ Is an anaerobic (no oxygen) process. ▪ Takes place in the cytoplasm 38 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 39 Glycolysis: Energy-Investment Phase In reactions 1-5 of glycolysis, ▪ Energy is required to add phosphate groups to glucose. ▪ Glucose is converted to two three-carbon molecules. 40  4 HO 1 3 HO 5 5 2 5 41 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings  G3P DHAP 42  Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings Glycolysis: Energy-Production Phase In reactions 6-10 of glycolysis, energy is generated as ▪ Sugar phosphates are cleaved to triose phosphates. ▪ Four ATP molecules are produced. Substrate-level phosphorylation (7,10) is the direct formation of ATP (or GTP) by transferring a phosphate group from a high energy compound to an ADP (or GDP) molecule. 43 DHAP 5 Glycolysis: Reactions 6-10 2 molecules 6 8 10 7 enolase 9 44 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 45 46 47 48 49 Glycolysis: Overall Reaction In glycolysis, ▪ Two ATP add phosphate to glucose and fructose-6-phosphate (Steps 1 and 3). ▪ Four ATP are formed in energy-generation by direct transfers of phosphate groups to four ADP (Steps 7 and 10; formation of 3-phosphoglycerate and pyruvate). ▪ There is a net gain of 2 ATP and 2 NADH. 50 Regulation of Glycolysis ▪ Glycolysis has three key regulatory steps (1, 3, and 10) catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase. These have large negative ΔG values and are essential to drive the overall flux to pyruvate. These regulatory steps are essentially irreversible. 52 Regulation of Glycolysis Glycolysis is regulated by three enzymes, ▪ Reaction 1 Hexokinase is inhibited by high levels of glucose-6- phosphate, which prevents the phosphorylation of glucose. ▪ Reaction 3 Phosphofructokinase, an allosteric enzyme, is inhibited by high levels of ATP and activated by high levels of ADP and AMP. If cells have plenty of ATP, glycolysis slows down. ▪ Reaction 10 Pyruvate kinase, another allosteric enzyme is inhibited by high levels of ATP or acetyl CoA. 53 Learning Check In glycolysis, what compounds provide phosphate groups for the production of ATP? 54 Solution In glycolysis, what compounds provide phosphate groups for the production of ATP? In reaction 7, phosphate groups from two 1,3-bisphosphoglycerate molecules are transferred to ADP to form two ATP. In reaction 10, phosphate groups from two phosphoenolpyruvate molecules are used to form two more ATP. 55 Fructose and Glycolysis ▪ Fructose is readily taken up in the muscle and liver. ▪ In the muscles, it is converted to fructose-6-phosphate, entering glycolysis at step 3. ▪ In the liver, it is converted to the trioses used in step 5. ▪ Fructose that enters a cell flows from reaction 5 to 10. ▪ Fructose uptake by the cells is not regulated by insulin: all fructose in the bloodstream is forced into catabolism. ▪ Glycolysis is regulated at step 3. The triose products created in the liver provide an excess of reactants that create excess pyruvate and acetyl CoA that, if not required for energy by the cells, is converted to fat. 56 Entry points for fructose and galactose into the glycolysis pathway. 57 Pathways for Pyruvate Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 58 59 Pyruvate: Aerobic Conditions Under aerobic conditions (oxygen present), ▪ Three-carbon pyruvate is decarboxylated. ▪ Two-carbon acetyl CoA and CO2 are produced. ▪ Occurs in the mitochondria Acetyl-CoA structure 60 Pyruvate: Aerobic Conditions ▪ Pyruvate is converted to acetyl CoA and NADH under aerobic conditions when oxygen is plentiful. The NADH is oxidized back to NAD+ to allow glycolysis to continue. 61 Pyruvate: Anaerobic Conditions Under anaerobic conditions (without oxygen), ▪ Pyruvate is reduced to lactate. ▪ NAD+ is produced and is used to oxidize more glyceraldehyde-3-phosphate in the glycolysis pathway, which produces a small but needed amount of ATP. ▪ Occurs in the cytosol 62 Lactate in Muscles During strenuous exercise, ▪ Oxygen in the muscles is depleted. ▪ Anaerobic conditions are produced. ▪ Lactate accumulates. After exercise, a person breathes heavily to repay the oxygen debt and reform pyruvate in the liver (lactate is transported to the liver). 63 64 Fermentation ▪ Occurs in anaerobic microorganisms such as yeast. ▪ Decarboxylates pyruvate to acetaldehyde, which is reduced to ethanol. ▪ Regenerates NAD+ to continue glycolysis. 65 Fermentation The first step in conversion of pyruvate to ethanol is a decarboxylation reaction to produce acetaldehyde. The second step involves acetaldehyde reduction to produce ethanol. 66 Pathways for Pyruvate 67 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings Learning Check Match the following terms with the descriptions A) Catabolic reactions B) Coenzymes C) Glycolysis D) Lactate 1. Produced during anaerobic conditions. 2. Reaction series that converts glucose to pyruvate. 3. Metabolic reactions that break down large molecules to smaller molecules + energy. 4. Substances that remove or add H atoms in oxidation and reduction reactions. 68 Solution Match the following terms with the descriptions: 1) Catabolic reactions 2) Coenzymes 3) Glycolysis 4) Lactate 1. D Produced during anaerobic conditions. 2. C Reaction series that converts glucose to pyruvate. 3. A Metabolic reactions that break down large molecules to smaller molecules + energy. 4. B Substances that remove or add H atoms in oxidation and reduction reactions. 69 Citric Acid Cycle The citric acid cycle (stage 3) ▪ Operates under aerobic conditions only. ▪ Oxidizes the two-carbon acetyl group in acetyl CoA to 2CO2. ▪ Produces reduced coenzymes NADH and FADH2 and one ATP directly. 70 Citric Acid Cycle Overview In the citric acid cycle, ▪ Acetyl (2C) bonds to oxaloacetate (4C) to form citrate (6C). ▪ Oxidation and decarboxylation reactions convert citrate to oxaloacetate. ▪ Oxaloacetate bonds with another acetyl to repeat the cycle. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 71  Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings oxidation condensation hydration isomerization oxidation Oxidative decarboxylation phosphorylation Oxidative 72 decarboxylation 73 Reaction 1: Formation of Citrate (Condensation) Oxaloacetate ▪ Combines with the two-carbon acetyl group to form citrate. COO- O COO- citrate CH2 synthase CH3 C SCoA + C O HO C COO- + HSCoA CH2 H C H COO- COO- acetyl CoA oxaloacetate citrate 74 Reaction 2: Isomerization to Isocitrate Citrate ▪ Isomerizes to isocitrate. ▪ Has a tertiary —OH group converted to a secondary —OH in isocitrate that can be oxidized. COO - COO - COO- CH2 CH2 CH2 H2O H2O HO C COO- C COO - H C COO- aconitase aconitase HO C H H C H CH COO - COO - COO- citrate aconitate isocitrate 75 Summary of Reactions 1 and 2 Copyright © 2007 by Pearson Education, Inc. 76 Publishing as Benjamin Cummings Reaction 3: Oxidative Decarboxylation Isocitrate ▪ Undergoes decarboxylation (carbon removed as CO2). ▪ Oxidizes the —OH to a ketone releasing H+ and 2e−. ▪ Provides H to reduce coenzyme NAD+ to NADH. COO- COO- isocitrate CH2 CH2 dehydrogenase H C COO- + NAD+ H C H + CO2 + NADH HO C H C O COO- COO- isocitrate -ketoglutarate 77 Reaction 4: Oxidative Decarboxylation -Ketoglutarate ▪ Undergoes decarboxylation to form succinyl CoA. ▪ Produces a 4-carbon compound that bonds to CoA. ▪ Provides H+ and 2e− to reduce NAD+ to NADH. COO- COO- CH2 -ketoglutarate dehydrogenase CH2 CH2 + NAD+ CH2 + CO2 + NADH C O C O + COO- CoASH S CoA -ketoglutarate succinyl CoA 78 Summary of Reactions 3 and 4 Copyright © 2007 by Pearson Education, Inc. 79 Publishing as Benjamin Cummings Reaction 5: Hydrolysis Succinyl CoA ▪ Undergoes breaking of the thioester bond. ▪ Provides energy to add phosphate to GDP and form GTP, a high-energy compound. COO- succinyl CoA COO- CH2 synthetase CH2 CH2 + GDP + Pi ++ CoASH CoA + GTP CH2 C O COO- S CoA ATP succinyl CoA succinate 80 Reaction 6: Dehydrogenation Succinate ▪ Undergoes dehydrogenation. ▪ Loses two H and forms a double bond. ▪ Provides 2H to reduce FAD to FADH2. COO- COO- succinate CH2 dehydrogenase C H + FAD + FADH2 CH2 H C COO - COO- succinate fumarate 81 Summary of Reactions 5 and 6 Copyright © 2007 by Pearson Education, Inc. 82 Publishing as Benjamin Cummings Reaction 7: Hydration of Fumarate Fumarate ▪ Undergoes hydration. ▪ Adds water to the double bond. ▪ Is converted to malate. COO- COO- C H HO C H fumarase H C + H2O H C H COO- COO- fumarate malate 83 Reaction 8: Dehydrogenation Malate ▪ Undergoes dehydrogenation. ▪ Forms oxaloacetate with a C=O double bond. ▪ Provides 2H that reduce NAD+ to NADH + H+. COO- malate COO- dehydrogenase HO C H + NAD+ C O + NADH + H+ H C H CH2 COO - COO- malate oxaloacetate 84 Summary of Reactions 7 and 8 Copyright © 2007 by Pearson Education, Inc. 85 Publishing as Benjamin Cummings Summary of the Citric Acid Cycle In the citric acid cycle, ▪ An acetyl group bonds with oxaloacetate to form citrate. ▪ Two decarboxylations remove two carbons as 2CO2. ▪ Four oxidations provide hydrogen for three (3) NADH and one (1) FADH2. ▪ A direct phosphorylation forms GTP (ATP). 86 Overall Chemical Reaction for the Citric Acid Cycle Step 1 Steps 3,4,8 Step 6 Step 5 Steps 1,7 acetyl-CoA + 3NAD+ + FAD + GDP + Pi + 2H2O Steps 3,4 2CO2 + 3NADH + 3H+ + FADH2 + HS-CoA + GTP One turn of the citric acid cycle produces: 2 CO2 1 GTP (1ATP) 3 NADH 1 HS-CoA 1 FADH2 87 Learning Check How many of each are produced in one turn of the citric acid cycle? A ___ CO2 B. ___ NADH C. ___ FADH2 D. ___ GTP 88 Solution How many of each are produced in one turn of the citric acid cycle? A 2 CO2 B. 3 NADH C. 1 FADH2 D. 1 GTP 89 Regulation of Citric Acid Cycle The reaction rate for the citric acid cycle ▪ Increases when low levels of ATP or NADH activate isocitrate dehydrogenase. ▪ Decreases when high levels of ATP or NADH inhibit citrate synthetase (first step in cycle). 90 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings  Electron Carriers Copyright © 2007 by Pearson Education, Inc. 91 Publishing as Benjamin Cummings Electron Carriers Electron carriers ▪ Are oxidized and reduced as hydrogen and/or electrons are transferred from one carrier to the next. ▪ Are FMN, Fe-S clusters, Coenzyme Q, and cytochromes. electron carrier AH2(reduced) electron carrier B (oxidized) electron carrier A (oxidized) electron carrier BH2(reduced) 92 Electron Carriers ▪ Accept hydrogen and electrons from the reduced coenzymes. ▪ Are oxidized and reduced to provide energy for the synthesis of ATP. 93 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings FMN (Flavin mononucleotide) FMN coenzyme ▪ Contains flavin, ribitol,and phosphate. ▪ Accepts 2H+ + 2e- to form reduced coenzyme FMNH2. Copyright © 2007 by Pearson Education, Inc. 94 Publishing as Benjamin Cummings Iron-Sulfur (Fe-S) Clusters Fe-S clusters ▪ Are groups of proteins containing iron ions and sulfide. ▪ Accept electrons to reduce Fe3+ to Fe2+, and lose electrons to re-oxidize Fe2+ to Fe3+. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 95 Coenzyme Q (Q or CoQ) Coenzyme Q (Q or CoQ) is ▪ A mobile electron carrier derived from quinone. ▪ Reduced when the keto groups accept 2H+ and 2e-. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 96 Cytochromes Cytochromes (cyt) are ▪ Proteins containing heme groups with iron ions. Fe3+ + 1e- Fe2+ ▪ Abbreviated as cyt a, cyt a3, cyt b, cyt c, and cyt c1. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 97 Learning Check Write the abbreviation for each: A. Reduced form of coenzyme Q. B. Oxidized form of flavin mononucleotide. C. Reduced form of iron in cytochrome c. 98 Solution Write the abbreviation for each: A. Reduced form of coenzyme Q. CoQH2 or QH2 B. Oxidized form of flavin mononucleotide. FMN C. Reduced form of cytochrome c. Cyt c (Fe2+) 99 Learning Check Indicate whether the electron carrier in each is oxidized or reduced: A. FMNH2 FMN B. Cyt b (Fe3+) Cyt b (Fe2+) C. Q QH2 D. Cyt c (Fe2+) Cyt c (Fe3+) 100 Solution Indicate whether the electron carrier in each is oxidized or reduced: A. FMNH2 FMN oxidized B. Cyt b (Fe3+) Cyt b (Fe2+) reduced C. Q QH2 reduced D. Cyt c (Fe2+) Cyt c (Fe3+) oxidized 101  Electron Transport Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 102 103 Electron Transport Electron transport ▪ Uses electron carriers. ▪ Transfers hydrogen ions and electrons from NADH and FADH2 until they combine with oxygen. ▪ Forms H2O. ▪ Produces ATP energy. 104 Electron Transport System In the electron transport system, ▪ The electron carriers are attached to the inner membrane of the mitochondrion. ▪ There are four protein complexes: Complex I NADH dehydrogenase Complex II Succinate dehydrogenase Complex III CoQ-Cytochrome c reductase Complex IV Cytochrome c oxidase 105 Electron Transport Chain Cyt c1 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 106 Electron Transport Chain Copyright © 2007 by Pearson Education, Inc. 107 Publishing as Benjamin Cummings Complex I NADH Dehydrogenase At Complex I, ▪ Hydrogen and electrons are transferred from NADH to FMN. NADH + H+ + FMN NAD+ + FMNH2 ▪ FMNH2 transfers hydrogen to Fe-S clusters and then to coenzyme Q reducing Q and regenerating FMN. Q + FMNH2 QH2 + FMN ▪ The overall reaction is NADH + H+ + Q NAD+ + QH2 ▪ QH2, a mobile carrier, transfers hydrogen to Complex III. 108 Complex II Succinate Dehydrogenase At Complex II, with a lower energy level than Complex I, ▪ FADH2 transfers hydrogen and electrons to coenzyme Q. ▪ Q is reduced to QH2 and FAD is regenerated. FADH2 + Q FAD + QH2 ▪ QH2, a mobile carrier, transfers hydrogen to Complex III. 109 Complex III: CoQ-Cytochrome c reductase At Complex III, Electrons are transferred from QH2 to two Cyt b. ▪ Each Cyt b (Fe3+) is reduced to Cyt b (Fe2+). ▪ Q is regenerated. 2Cyt b (Fe3+) + QH2 2Cyt b (Fe2+) + Q + 2H+ Electrons are transferred from Cyt b to Fe-S clusters, to Cyt c1, and to Cyt c, the second mobile carrier. 2Cyt c (Fe3+) + 2Cyt b (Fe2+) 2Cyt c (Fe2+) + 2Cyt b (Fe3+) 110 Complex IV: Cytochrome c Oxidase At Complex IV, electrons are transferred from: ▪ Cyt c to Cyt a. 2Cyt c (Fe2+) + 2Cyt a (Fe3+) 2Cyt c (Fe3+) + 2Cyt a (Fe2+) ▪ Cyt a to Cyt a3. 2Cyt a (Fe2+) + 2Cyt a3 (Fe3+) 2Cyt a (Fe3+) + 2Cyt a3 (Fe2+) ▪ Cyt a3 to oxygen and H+ to form water. 4H+ + O2 + 4e- (from Cyt a3 ) 2H2O 111 Learning Check Match each with their function: A) FMN B) Q C) Cyt c 1. Accepts H and electrons from NADH + H+. 2. A mobile carrier between Complex III and IV. 3. Carries electrons from Complex I and II to Complex III. 4. Accepts H and electrons from FADH2. 112 Solution Match each with their function: A) FMN B) Q C) Cyt c 1. A Accepts H and electrons from NADH + H+. 2. C A mobile carrier between Complex III and IV. 3. B Carries electrons from Complex I and II to Complex III. 4. B Accepts H and electrons from FADH2. 113 Learning Check Classify each as a product of the A) Citric acid cycle B) Electron transport chain 1. CO2 2. FADH2 3. NAD+ 4. NADH 5. H2O 114 Solution Classify each as a product of the A) citric acid cycle B) electron transport chain 1. A CO2 2. A FADH2 3. B NAD+ 4. A NADH 5. B H2O 115 Oxidative Phosphorylation and ATP Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 116  Chemiosmotic Model In the chemiosmotic model ▪ Complexes I, III, and IV pump protons into the intermembrane space creating a proton gradient. ▪ Protons pass through ATP synthase to return to the matrix. ▪ The flow of protons through ATP synthase provides the energy for ATP synthesis (oxidative phosphorylation): ADP + Pi + Energy ATP 117 Chemiosmotic Model of Electron Transport 2.5 ADP + 2.5 Pi 2.5 ATP Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 118 ATP Synthase In ATP synthase ▪ Protons flow back to the matrix through a channel in the F0 complex. ▪ Proton flow provides the energy that drives ATP synthesis by the F1 complex. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 119 ATP Synthase F1 Complex In the F1 complex of ATP synthase ▪ A center subunit () is surrounded by three protein subunits: loose (L), tight (T), and open (O). ▪ Energy from the proton flow through F0 turns the center subunit (). ▪ The shape (conformation) of the three subunits changes. 120 ATP Synthesis in F1 During ATP synthesis ▪ ADP and Pi enter the loose L site. ▪ The center subunit turns changing the L site to a tight T conformation. ▪ ATP is formed in the T site where it remains strongly bound. ▪ The center subunit turns changing the T site to an open O site, which releases the ATP. 121 ATP Synthase F1 Diagram Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 122 Learning Check Match the following A) F0 complex B) F1 complex C) L site D) T site E) O site 1. Contains subunits for ATP synthesis. 2. Contains the channel for proton flow. 3. The subunit in F1 that binds ADP and Pi. 4. The subunit in F1 that releases ATP. 5. The subunit in F1 where ATP forms. 123 Solution Match the following A) F0 complex B) F1 complex C) L site D) T site E) O site 1. B Contains subunits for ATP synthesis. 2. A Contains the channel for proton flow. 3. C The subunit in F1 that binds ADP and Pi. 4. E The subunit in F1 that releases ATP. 5. D The subunit in F1 where ATP forms. 124 Electron Transport and ATP In electron transport, the energy level decrease for electrons ▪ From NADH (Complex I) provides sufficient energy for 2.5 ATPs. NADH + 2.5 ADP + 2.5 Pi NAD+ + 2.5 ATP ▪ From FADH2 (Complex II) provides sufficient energy for 1.5 ATPs. FADH2 + 1.5 ADP + 1.5 Pi FAD + 1.5 ATP 125 ATP from Electron Transport Copyright © 2007 by Pearson Education, Inc. 126 Publishing as Benjamin Cummings Regulation of Electron Transport The electron transport system is regulated by ▪ Low levels of ADP, Pi, oxygen, and NADH that decrease electron transport activity. ▪ High levels of ADP that activate electron transport. 127  ATP Energy from Glucose Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 128 ATP Energy from Glucose The complete oxidation of glucose yields ▪ 6 CO2 ▪ 6 H2O ▪ 32 ATP 129 ATP from Glycolysis Reaction Pathway ATP for One Glucose ATP from Glycolysis Activation of glucose -2 ATP Oxidation of 2 NADH 5 ATP Direct ADP phosphorylation (two triose) 4 ATP 7 ATP Summary: C6H12O6 2 pyruvate + 2H2O + 7 ATP glucose 131 ATP from Two Pyruvate Under aerobic conditions ▪ 2 pyruvate are oxidized to 2 acetyl CoA and 2 NADH. ▪ 2 NADH enter electron transport to provide 5 ATP. Summary: 2 Pyruvate 2 Acetyl CoA + 5 ATP 132 ATP from Citric Acid Cycle ▪ One turn of the citric acid cycle provides: 3 NADH x 2.5 ATP = 7.5 ATP 1 FADH2 x 1.5 ATP = 1.5 ATP 1 GTP x 1 ATP = 1 ATP Total = 10 ATP Acetyl CoA 2 CO2 + 10 ATP ▪ For two acetyl CoA from one glucose, two turns of the citric acid cycle produce 20 ATP. 2 Acetyl CoA 4 CO2 + 20 ATP 133 ATP from Citric Acid Cycle Reaction Pathway ATP (One Glucose) ATP from Citric Acid Cycle Oxidation of 2 isocitrate (2NADH) 5 ATP Oxidation of 2 -ketoglutarate (2NADH) 5 ATP 2 Direct substrate phosphorylations (2GTP) 2 ATP Oxidation of 2 succinate (2FADH2) 3 ATP Oxidation of 2 malate (2NADH) 5 ATP Summary: 2Acetyl CoA 4CO2 + 2H2O + 20 ATP 134 ATP from Glucose One glucose molecule undergoing complete oxidation provides: From glycolysis 7 ATP From 2 pyruvate 5 ATP From 2 acetyl CoA 20 ATP Overall ATP Production for one glucose C6H12O6 + 6O2 + 36ADP + 36Pi glucose 6CO2 + 6H2O + 32 ATP 135 Learning Check Indicate the ATP yield for each under aerobic conditions. A. Complete oxidation of glucose B. FADH2 C. Acetyl CoA in citric acid cycle D. NADH E. Pyruvate decarboxylation 136 Solution Indicate the ATP yield for each under aerobic conditions. A. Complete oxidation of glucose 32 ATP B. FADH2 1.5 ATP C. Acetyl CoA in citric acid cycle 10 ATP D. NADH 2.5 ATP E. Pyruvate decarboxylation 2.5 ATP 137 Metabolic Pathways for Lipids and Amino Acids Digestion of Triacylglycerols Copyright © 2007 by Pearson Education, Inc. 138 Publishing as Benjamin Cummings Digestion of Fats (Triacylglycerols) In the digestion of fats (triacylglycerols), ▪ Bile salts break fat globules into smaller particles called micelles in the small intestine. ▪ Pancreatic lipases hydrolyze ester bonds to form monoacylglycerols and fatty acids, which recombine in the intestinal lining. ▪ Fatty acids bind with proteins forming lipoproteins to transport triacylglycerols to the cells of the heart, muscle, and adipose tissues. ▪ The chylomicrons transport the triacylglycerols to the cells of the heart, muscle, and adipose tissues. When energy is needed in the cells, enzymes hydrolyze the triacylglycerols to yield glycerol and fatty acids. 139 Digestion of Triacylglycerols 140 Fat Mobilization Fat mobilization ▪ Breaks down triacylglycerols in adipose tissue. ▪ Forms fatty acids and glycerol. ▪ Hydrolyzes fatty acid initially from C1 or C3 of the fat. triacylglycerols + 3 H2O glycerol + 3 fatty acids 141 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings Metabolism of Glycerol Glycerol from fat digestion ▪ Adds a phosphate from ATP to form glycerol-3-phosphate. ▪ Undergoes oxidation of the –OH group to dihydroxyacetone phosphate. ▪ Becomes an intermediate used in glycolysis and gluconeogenesis. Glycerol + ATP + NAD+ dihydroxyacetone phosphate + ADP + NADH + H+ 142 Oxidation of Glycerol Glycolysis 143 Learning Check Give answers for the following questions on fat digestion. 1. What is the function of bile salts in fat digestion? 2. Why are the triacylglycerols in the intestinal lining coated with proteins to form chylomicrons? 3. How is glycerol utilized? 144 Solution 1. What is the function of bile salts in fat digestion? Bile salts break down fat globules allowing pancreatic lipases to hydrolyze the triacylglycerol. 2. Why are the triacylglycerols in the intestinal lining coated with proteins to form chylomicrons? The proteins coat the triacylglycerols to make water-soluble chylomicrons that move into the lymph and bloodstream. 3. How is glycerol utilized? Glycerol adds a phosphate and is oxidized to an intermediate of the glycolysis pathway. 145  Oxidation of Fatty acids and ATP and Fatty Acid Oxidation Copyright © 2007 by Pearson Education, Inc. 146 Publishing as Benjamin Cummings Fatty Acid Activation Fatty acid activation ▪ Allows the fatty acids in the cytosol to enter the mitochondria for oxidation. ▪ Combines a fatty acid with CoA to yield fatty acyl-CoA that combines with carnitine. Fatty acyl Copyright © 2007 by Pearson Education, Inc. 147 Publishing as Benjamin Cummings Transport of Fatty Acyl CoA ▪ Fatty acyl-CoA forms fatty acyl-carnitine that transports the fatty acyl group into the matrix. ▪ The fatty acyl group recombines with CoA for oxidation. 148 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings Summary of Fatty Acid Activation ◼ Fatty acid activation is complex, but it regulates the degradation and synthesis of fatty acids. Fatty acyl 149 Beta-Oxidation of Fatty Acids Reaction 1, Dehydrogenation. The first reaction removes one hydrogen from the alpha and beta carbons, and a double bond is formed. These hydrogens are transferred to FAD to form FADH2. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 150 Beta-Oxidation of Fatty Acids Reaction 2, Hydration. In reaction 2, water is added to the  and β carbon double bond as –H and –OH, respectively. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 151 Beta-Oxidation of Fatty Acids Reaction 3, Oxidation. The alcohol formed on the β carbon is oxidized to a ketone. As we have seen before in the citric acid cycle, the hydrogen from the alcohol reduces NAD+ to NADH. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 152 Beta-Oxidation of Fatty Acids Reaction 4, Cleavage. In the fourth reaction of the cycle, the bond between the  and β carbon is broken and a second CoA is added, forming an acetyl CoA and a fatty acyl CoA shortened by two carbons. The fatty acyl CoA can be run through the cycle again. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 153 Learning Check Match the reactions of -oxidation with each: 1) oxidation 1 2) hydration 3) oxidation 2 4) cleavage A. Water is added. B. FADH2 forms. C. A two-carbon unit is removed. D. A hydroxyl group is oxidized. E. NADH forms. 154 Solution Match the reactions of -oxidation with each: 1) oxidation 1 2) hydration 3) oxidation 2 4) acetyl CoA cleaved A. 2 Water is added. B. 1 FADH2 forms. C. 4 A two-carbon unit is removed. D. 3 A hydroxyl group is oxidized. E. 3 NADH forms. 155 Beta()-Oxidation of Myristic (C14) Acid 156 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings  Beta()-Oxidation of Myristic (C14) Acid (continued) C14 6 7 Acetyl cycles CoA 157 Fatty Acid Length and -Oxidation The length of a fatty acid ▪ Determines the number of oxidations ▪ Determines the total number of acetyl CoA groups. Carbons in Acetyl CoA -Oxidation Cycles Fatty Acid (#C/2) (#C/2 –1) 12 6 5 14 7 6 16 8 7 18 9 8 158 Learning Check 1. The number of acetyl CoA groups produced by the complete -oxidation of palmitic acid (C16 ): A) 16 B) 8 C) 7 2. The number of oxidation cycles to completely oxidize palmitic acid (C16 ): A) 16 B) 8 C) 7 159 Solution 1. The number of acetyl CoA groups produced by the complete -oxidation of palmitic acid (C16 ): B) 8 (16 C/2 = 8) 2. The number of oxidation cycles to completely oxidize palmitic acid (C16 ): C) 7 (16 C/2 -1 = 7) 160 ATP and -Oxidation Activation of a fatty acid requires 2 ATP One cycle of oxidation of a fatty acid produces 1 NADH 2.5 ATP 1 FADH2 1.5 ATP Acetyl CoA entering the citric acid cycle produces 1 Acetyl CoA 10 ATP 161 162 ATP for Lauric Acid C12 ATP production for lauric acid (12 carbons): Activation of lauric acid -2 ATP 6 Acetyl CoA 6 acetyl CoA x 10 ATP/acetyl CoA 60 ATP 5 Oxidation cycles 5 NADH x 2.5 ATP/NADH 12.5 ATP 5 FADH2 x 1.5 ATP/FADH2 7.5 ATP Total 78 ATP 163 Learning Check The total ATP produced from the -oxidation of stearic acid (C18) is A) 98 ATP B) 120 ATP C) 148 ATP 164 Solution The total ATP produced from the -oxidation of stearic acid (C18) is: B) 120 ATP Activation -2 ATP 9 Acetyl CoA x 10 ATP 90 ATP 8 NADH x 2.5 ATP 20 ATP 8 FADH2 x 1.5 ATP 12 ATP 120 ATP 165 Ketogenesis and Ketone Bodies Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 166 Ketone Bodies If carbohydrates are not available ▪ Body fat breaks down to meet energy needs. Ketone ▪ Keto compounds bodies called ketone bodies form. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cumming 167 Ketone Bodies Ketone bodies are produced mostly in the liver and transported to cells in the heart, brain, Ketone and skeletal muscle, bodies where small amounts of energy can be obtained by converting acetoacetate or hydroxybutyrate Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cumming back to acetyl CoA 168 Ketogenesis In ketogenesis ▪ Large amounts of acetyl CoA accumulate. ▪ Two acetyl CoA molecules combine to form acetoacetyl CoA. ▪ Acetoacetyl CoA hydrolyzes to acetoacetate, a ketone body. ▪ Acetoacetate reduces to -hydroxybutyrate or loses CO2 to form acetone, both ketone bodies. 169 Reactions of Ketogenesis Ketone bodies Copyright © 2007 by Pearson Education, Inc. 170 Publishing as Benjamin Cummings Ketosis Ketosis occurs ▪ In diabetes, diets high in fat, and starvation. ▪ As ketone bodies accumulate. ▪ When acidic ketone bodies lowers blood pH below 7.4 (acidosis). Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 171 Ketone Bodies and Diabetes In diabetes ▪ Insulin does not function properly. ▪ Glucose levels are insufficient for energy needs. ▪ Fats are broken down to acetyl CoA. ▪ Ketogenesis produces ketone Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings bodies. 172 Ketone Bodies and Diabetes In all types of diabetes, insufficient amounts of glucose are available in the muscle, liver, and adipose tissue. As a result, liver cells synthesize glucose from noncarbohydrate sources (gluconeogenesis) and break down fat, elevating the acetyl CoA level. Excess acetyl CoA undergoes ketogenesis, and ketone bodies accumulate in the blood. As the level of acetone increases, its odor can be detected on the breath of a person with uncontrolled diabetes who is in ketosis. 173 Learning Check In ketogenesis, match the type of reaction with 1) oxidation 2) reduction 3) decarboxylation A. acetoacetate produces acetone B. acetoacetate produces β-hydroxybutyrate 174 Solution In ketogenesis, match the type of reaction with 1) oxidation 2) reduction 3) decarboxylation A. acetoacetate produces acetone 3 B. acetoacetate produces β-hydroxybutyrate 2 175  Digestion of Proteins and Degradation of Amino Acids Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 176 Digestion of Proteins The digestion of proteins (stage 1) ▪ Begins in the stomach where HCl in stomach acid activates pepsin to hydrolyze peptide bonds. ▪ Continues in the small intestine where trypsin and chymotrypsin hydrolyze peptides to amino acids. ▪ Is complete as amino acids enter the bloodstream for transport to cells. 177 Digestion of Proteins Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 178 Learning Check Match the end products of digestion with the types of food: 1. amino acids 2. fatty acids and glycerol 3. glucose A. fats B. proteins C. carbohydrates 179 Solution Match the end products of digestion with the types of food: 1. amino acids 2. fatty acids and glycerol 3. glucose A. fats 2. fatty acids and glycerol B. proteins 1. amino acids C. carbohydrates 3. glucose 180 Proteins in the Body Proteins provide ▪ Amino acids for protein synthesis. ▪ Nitrogen atoms for nitrogen-containing compounds. ▪ Energy when carbohydrate and lipid resources are not available. Copyright © 2007 by Pearson Education, Inc. 181 Publishing as Benjamin Cummings Transamination In transamination ▪ Amino acids are degraded in the liver. ▪ An amino group is transferred from an amino acid to an -keto acid, usually -ketoglutarate. ▪ The reaction is catalyzed by a transaminase or aminotransferase. ▪ A new amino acid, usually glutamate, and a new -keto acid are formed. 182 A Transamination Reaction NH3+ O alanine | || aminotransferase CH3—CH—COO- + -OOC—C—CH2—CH2—COO- alanine -ketoglutarate O NH3+ || | CH3—C—COO- + -OOC—CH—CH —CH —COO- 2 2 pyruvate glutamate 183 Oxidative Deamination Oxidative deamination ▪ Removes the amino group as an ammonium ion from glutamate. ▪ Provides -ketoglutarate for transamination. NH3+ glutamate | dehydrogenase -OOC—CH—CH —CH —COO- + NAD+ + H O 2 2 2 glutamate O || -OOC—C—CH —CH —COO- + NH + + NADH 2 2 4 -ketoglutarate 184 Learning Check Write the products from the transamination of -ketoglutarate by aspartate. NH3+ | -OOC—CH—CH —COO- 2 aspartate O || -OOC—C—CH —CH —COO- 2 2 -ketoglutarate 185 Solution Write the products from the transamination of -ketoglutarate by aspartate. O || -OOC—C—CH —COO- 2 oxaloacetate NH3+ | -OOC—CH—CH —CH —COO- 2 2 glutamate 186 Urea Cycle O || H2N—C—NH2 urea 187 Urea Cycle The urea cycle ▪ Detoxifies ammonium ion from amino acid degradation. ▪ Converts ammonium ion to urea in the liver. O || H2N—C—NH2 urea ▪ Provides 25-30 g urea daily for urine formation in the kidneys. 188 Carbamoyl Phosphate Carbamoyl phosphate is formed ▪ In the mitochondria, when ammonium ion reacts with CO2 from the citric acid cycle, 2 ATP, and water. carbomyl phosphate synthetase NH4+ + CO2 + 2ATP + H2O O O || || H2N—C—O—P—O- + 2ADP + Pi | O- 189 carbamoyl phosphate Reaction 1 Transfer of Carbamoyl Group In reaction 1 of the urea cycle, ▪ The carbamoyl group is transferred to ornithine to form citrulline. ▪ Citrulline moves across the mitochondrial membrane into the cytosol. 190 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings Reaction 2 Condensation with Aspartate In reaction 2 of the urea cycle, ▪ That takes place in the cytosol, citrulline combines with aspartate. ▪ Hydrolysis of ATP to AMP provides energy. Cytosol ▪ The N in aspartate is part of urea. 191 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings Reaction 3 Cleavage of Fumarate In reaction 3 of the urea cycle, fumarate ▪ Is cleaved from argininosuccinate. ▪ Enters the citric acid cycle. 192 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings Reaction 4 Hydrolysis Forms Urea In reaction 4 of the urea cycle, ▪ Arginine is hydrolyzed ▪ Urea forms. ▪ Ornithine returns to the mitochondrion to pick up another carbamoyl group to repeat the urea cycle. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 193  Urea Cycle 194 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings Summary of Urea Cycle The urea cycle converts: ▪ Ammonium ion to urea ▪ Aspartate to Fumarate ▪ 3ATP to 2ADP, AMP, 4Pi NH4+ + CO2 + 3ATP + aspartate + 2H2O urea + 2ADP + AMP + 4Pi + fumarate 195 Learning Check Identify the site for each as: 1) mitochondrion 2) cytosol A. Formation of urea. B. Formation of carbamoyl phosphate. C. Aspartate combines with citrulline. D. Fumarate is cleaved. E. Citrulline forms. 196 Solution Identify the site for each as: 1) mitochondrion 2) cytosol A. 2 Formation of urea. B. 1 Formation of carbamoyl phosphate. C. 2 Aspartate combines with citrulline. D. 2 Fumarate is cleaved. E. 1 Citrulline forms. 197 Fates of the Carbon Atoms from Amino Acids Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 198 Carbon Atoms from Amino Acids When needed, carbon skeletons of amino acids are used to produce energy by forming intermediates of the citric acid cycle. ▪ Three-carbon skeletons alanine, serine, and cysteine pyruvate ▪ Four-carbon skeletons aspartate, asparagine oxaloacetate ▪ Five-carbon skeletons glutamine, glutamate, proline, arginine, histidine glutamate 199 Glucogenic and Ketogenic Amino Acids Amino acids are classified as ▪ Glucogenic if they generate pyruvate or oxaloacete, which can be used to synthesize glucose. ▪ Ketogenic if they generate acetoacetyl CoA or acetyl CoA, which can form ketone bodies or fatty acids. 200 Amino Acid Pathways to Citric Acid Intermediates Ketogenic Glucogenic 201 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings Amino Acid Pathways to Pyruvate and Oxaloacetate Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 202 Glucogenic Amino Acids that Form Intermediates of the Citric Acid Cycle 203 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 204 Learning Check Match each the intermediate with the amino acid that provides its carbon skeleton. 1) pyruvate 2) fumarate 3) -ketoglutarate A. cysteine B. glutamine C. aspartate D. serine 205 Solution Match each the intermediate with the amino acid that provides its carbon skeleton. 1) pyruvate 2) fumarate 3) -ketoglutarate A. 1 cysteine B. 3 glutamine C. 2 aspartate D. 1 serine 206 Learning Check Identify each as glucogenic (G) or ketogenic (K) A. alanine B. lysine C. phenylalanine D. aspartate E. glutamate 207 Solution Identify each as glucogenic (G) or ketogenic (K) A. G alanine B. K lysine C. K phenylalanine D. G aspartate E. G glutamate 208 Overview of Metabolism In metabolism ▪ Catabolic pathways degrade large molecules. ▪ Anabolic pathway synthesize molecules. ▪ Branch points determine which compounds are degraded to acetyl CoA to meet energy needs or converted to glycogen for storage. ▪ Excess glucose is converted to body fat. ▪ Fatty acids and amino acids are used for energy when carbohydrates are not available. ▪ Some amino acids are produced by transamination. 209  210 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings