Chapter 25! Chapter 25 - Metabolism! Metabolism and Energetics! SECTION 25-1! Metabolism refers to all the chemical reactions that occur in the body!

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1 Chapter 25! Metabolism and Energetics! Portions of this chapter and some additional information! SECTION 25-1! Metabolism refers to all the chemical reactions that occur in the body! 2 Nutrients! Nutrients are substances that are:! 1. Used to supply energy for energy-requiring processes. For example:! DNA and protein synthesis! Active transport! Muscle contraction, etc.! 2. Used as building blocks for synthetic processes! e.g. amino acids proteins! 3. Stored for future use for #1 and #2! Glucose stored as glycogen! Triglycerides stored as fat! 3 1!

2 Classes of Nutrients and Breakdown Products! 1. Carbohydrates monosaccharides! 2. Triglycerides (lipids) fatty acids + glycerol! 3. Proteins amino acids! 4. Minerals: inorganic, may be parts of enzyme systems! 5. Vitamins: organic, most are coenzymes! 6. Water! 4 Metabolism! Sum of all chemical reactions occurring in the body! Anabolic reactions Require input of energy (endergonic)! Synthesize complex molecules from simpler ones! Catabolic reactions Release energy (exergonic)! Break down complex molecules into simpler ones! Glycolysis, Krebs cycle, electron transport chain! 5 Metabolism 2! Both types of reactions require enzymes.! Energy derived from catabolism is used to drive anabolism.! Efficiency about 40%! (i.e. 60% lost as heat)! Much higher than human-made machines! 6 2!

3 Introduction to Cellular Metabolism Figure 25-1! Heat! 60%! ATP! 40%! 7 SECTION 25-7! Metabolic rate is the average caloric expenditure, and thermoregulation involves balancing heat-producing and heat-losing mechanisms! Metabolic rate = overall rate at which heat is produced by the body!! **Measured directly as heat production or! indirectly as O 2 uptake! 8 Basal Metabolic Rate (BMR)! The basal metabolism of an animal is the minimal rate of energy expenditure compatible with life.! Subject must be:! Quiet no muscular activity! Rested (8h sleep night before)! Fasting (postabsorptive state)! At a thermoneutral ambient temperature! BMR lowest during menses, highest just before! 9 3!

4 ! Chapter 25 - Metabolism! Heat vs. Temperature! Heat = total kinetic energy of a substance! Measured in calories or kilocalories! Temperature = average kinetic energy of a substance! Measured in C (or F)! 10 Calorimetry! Direct calorimetry! Measures heat produced by metabolism! Indirect calorimetry! Measures O 2 uptake (or CO 2 production)! Is proportional to amount of heat produced! nutrient! kcal heat per l O 2! carbohydrate! 5.0! protein! 4.6! lipid! 4.6! typical diet! 4.9! I.e., energy yield per l O 2 is about the same so it s a good measure of heat production.! 11 Calorimetry 2! Information from the previous table can be used to indirectly calculate BMR! Note that there is much more energy per gram of fat than per gram of other substrates. But it takes more oxygen to burn it so the energy yield per liter of oxygen is about the same for both (pervious slide).! Nutrient Kcal heat Liters O 2 per gram per gram Carbohydrate Protein Lipid !

5 Factors influencing BMR! 1. Exercise: increases V O2 (V O2 = oxygen consumption)! 2. Hormones: thyroxine, testosterone V O2! 3. Nervous input: sympathetic stimulation V O2! 4. Increased T body : V O2! 5. Ingestion of food: V O2 (called specific dynamic reaction )! 6. Age: mass specific metabolic rate with age! 7. Gender: lower in females except during pregnancy, lactation! 8. Diurnal fluctuation: lower during sleep (when T body is lower)! 13 Effects of Environmental Temperature on V O2! * * Oxygen consumption in ml O 2 / kg hr! 14 Body Temperature Regulation! 1. Relatively constant core temperature of about! 37 C, but varies with time of day, exercise! 2. Surface of body or shell cooler! Allows for dissipation of metabolicallyproduced heat.! Preoptic/anterior hypothalamic nuclei important! Respond to changes in brain temperature! Receive inputs from peripheral and central receptors! Compare inputs to optimal temperature! Send signals to effector organs (What are some of these effector organs?)! 15 5!

6 Hypothalamic Thermostat! Has a predictive function (feedforward control)! A change in T body is not required in order to activate heat gain or heat loss mechanisms.! Peripheral receptors send info to hypothalamus and it predicts the response necessary to prevent a change in T body.! 16 Heat Gain (Retention/Production)! If hypothalamus receives inputs indicating that T body is falling or is likely to do so! 1. Behavioral responses! Seek out warm environment, put on clothes! 2. Vasoconstriction of peripheral vessels! Reduce heat loss! 3. Sympathetic stimulation (NE, E)! Increase metabolic rate; heat production! 4. Increase thyroid hormone release in cold environment! Increase metabolic rate; heat production! 17 Heat Loss Mechanisms! If hypothalamus receives inputs indicating that T body is rising or is likely to do so! 1. Behavioral responses! Seek cooler environment! 2. Vasodilation of peripheral vessels! Increase loss to environment! 3. Sweat! See Evaporation below! 4. Other animals pant or spread saliva!! Note that behavioral responses are activated first.! 18 6!

7 !! Chapter 25 - Metabolism! Avenues of Heat Exchange! 1. Radiation! Transfer of infrared radiation (heat) from warmer to cooler objects that are not in physical contact! 2. Conduction! e.g., heat from camp fire! Transfer of heat from warmer to cooler objects that are in physical contact! e.g., sitting on a block of ice! 19 Avenues of Heat Exchange - 2! 3. Convection! Transfer of heat between an object and a moving fluid like air or water! 4. Evaporation! e.g., being outside without a coat on a cold, windy day! Conversion of liquid water into water vapor requires a lot of heat energy.! Sweating removes heat from the body! 20 Abnormalities of body temperature! Hyperthermia - higher than normal body temperature. This refers to an unregulated, abnormal increase! Hypothermia - lower than normal body temperature. This refers to an unregulated, abnormal decrease.! Fever is a regulated increase in body temperature.! 21 7!

8 ! Chapter 25 - Metabolism! SECTION 25-2! Carbohydrate metabolism involves glycolysis, ATP production, and gluconeogenesis! 22 Oxidation-Reduction Reactions! Oxidation is the removal of electrons from a substrate! In biological reactions, oxidations usually involve the removal of 2 hydrogen atoms (2H) in the form of a proton (H + ) and a hydride ion (H - = H e - )! Because H atoms are removed, biological oxidation reactions are also called dehydrogenation reactions! Reduction is the addition of electrons to a substrate.! 23 Electron (or H atom) carriers! The symbol represents the two electrons that are moving.! Two important coenzymes that do this are:! 1. NAD + (Nicotinamide adenine dinucleotide)! NAD H NADH + H +! (oxidized) (reduced)! 2. FAD (Flavin adenine dinucleotide)! FAD + 2 H FADH 2! (oxidized) (reduced)!! Remember that both of the reduced coenzymes carries a pair of electrons.! 24 8!

9 Methods of ATP Generation! 1. Substrate level phosphorylation! A phosphate is transferred from one substrate (metabolic intermediate) to ADP! 2. Oxidative phosphorylation! a) Electrons move from high energy carriers (like NADH NAD e - ) to progressively lower energy carriers in the electron transport chain of the mitochondrion. The electrons wind up on oxygen (i.e. oxidative).! b) The energy released as the electrons move along the chain is used to produce a H + gradient across the mitochondrial inner membrane.! 25 Methods of ATP Generation 2! c) When H + diffuses down its concentration gradient through the membrane protein, ATP synthase, the energy released is used to phosphorylate ADP to ATP.! 3. Photophosphorylation! Plants and some bacteria can use light energy to produce ATP.! Human s can t do this, so you don t get to learn about this in A&P.! 26 Glucose Movement into Cells! 1. G.I. tract and kidney tubules! Secondary active transport via Na + /glucose symporters (cotransporters) and! 2. Other cells! Facilitated diffusion! Insulin increases rate of uptake except in neurons and hepatocytes where glucose entry is always turned on! Phosphorylation of glucose to glucose 6-phosphate traps glucose inside cells! It s no longer just glucose so it can t bind to transporters! 27 9!

10 Glucose Catabolism (Oxidation of Glucose)! C 6 H 12 O O ADP + 36 P i! 6 CO H 2 O + 36 ATP + heat! Occurs in three stages:! 1. Glycolysis - anaerobic cellular metabolism (O 2 not required)! 2. Krebs cycle = citric acid cycle = tricarboxylic acid (TCA) cycle! Initial part of aerobic cellular metabolism! 3. Electron transport chain! Second part of aerobic metabolism! Both #2 and #3 require O 2! 28 Glycolysis Overview 1! This process occurs in the cytoplasm! (Note: the units of measurement are actually moles, not individual molecules)! 1. What goes in:! 1 glucose (6 carbons)! 2 ATP! 2 NAD +! 29 Glycolysis Overview 2! 2. What comes out:! 2 pyruvate (3 carbons each)! 4 ATP! 2 NADH + 2 H +! 3. Net gains:! 2 ATP by substrate level phosphorylation! 2 Pyruvate to send to Krebs cycle in mitochondria if O 2 is available! 2 NADH carrying electrons to send to electron transport chain if O 2 is available! 30 10!

11 Glycolysis Figure 25-3! The glycolysis part of your metabolic pathways assignment does not include the portions of this figure that are surrounded by the dashed lines.! 31 The Fate of Pyruvate Depends Upon O 2 Availability! 1. If O 2 is not available to mitochondria! Pyruvate is reduced to lactic acid in the cytoplasm! This regenerates NAD + (oxidizes NADH) that is required to allow glycolysis to continue producing small amounts of ATP anaerobically.! NAD + can be used! by glycolytic! reactions! 32 The Fate of Pyruvate 2! 2. If O 2 is available to the mitochondria! Pyruvate (3 carbons) is oxidized by NAD + to acetate (2 carbons) with the loss of CO 2! Acetate combines with Coenzyme A, forms acetyl-coa and enters Krebs cycle! I am calling this the pyruvate-to-acetate step on your summary sheet.! 33 11!

12 Krebs Cycle (the TCA Cycle) Figure 25-4b! Note error in 9 th edition: there s an NADH missing near pyruvate.! 2 carbons! Pyruvate lost a CO 2! 4 carbons! 4 carbons! 3 carbons - from glycolysis! 6 carbons: = 6! 6 carbons! 2x per glucose! 4 carbons! 5 carbons! Lost a CO 2! Note error in 8 th edition: citrate and isocitrate are 6-carbon molecules.! 4 carbons! P i 4 carbons! Lost a CO 2! 34 Pyruvate-to-Acetate Step! This reaction links glycolysis with Krebs cycle! This reaction takes place in the mitochondria! What goes in (for each glucose):! 2 pyruvate enter mitochondrion! 2 NAD + used to oxidize pyruvates! What comes out (for each glucose):! Two acetates (acetyl groups)! 2 CO 2 s released! 2 NADH (+ 2 H + ) carrying electrons to electron transport chain! 35 Krebs Cycle Overview! These reactions occur in the mitochondrial matrix! What goes in (for each glucose):! Two 2-carbon acetate molecules combined with Coenzyme A = acetyl-coenzyme A! These are added to the final 4-carbon intermediate of the cycle (oxaloacetate) to produce the first 6-carbon intermediate (citrate) (2C + 4C = 6C)! 6 NAD +! 2 FAD! 2 ADP + P i (actually GDP, but the result is the same! 36 12!

13 Krebs Cycle Overview 2! What comes out (for each glucose):! 4 CO 2 s generated by dehydrogenation reactions! 6 NADH + 6 H + (carrying electrons)! 2 FADH 2 (carrying electrons)! 2 ATP (by substrate level phosphorylation)! 37 Krebs Cycle (the TCA Cycle) Figure 25-4b! Note error in 9 th edition: there s an NADH missing near pyruvate.! 2 carbons! Pyruvate lost a CO 2! 4 carbons! 4 carbons! 3 carbons - from glycolysis! 6 carbons: = 6! 6 carbons! 2x per glucose! 4 carbons! 5 carbons! Lost a CO 2! Note error in 8 th edition: citrate and isocitrate are 6-carbon molecules.! 4 carbons! P i 4 carbons! Lost a CO 2! 38 Electron Transport Chain Overview! These reactions occur in or on the inner mitochondrial membrane! Electrons carried by NADH or FADH 2 are at a very high energy level (highly reduced) compared to those of molecular O 2.! The electrons are passed from NADH or FADH 2 to electron carriers in or on the inner mitochondrial membrane. The electrons are passed from higher energy carriers to lower energy carriers, and finally down to O 2. This releases energy (originally stored in the covalent bonds of nutrients) in small increments rather than in a large blast that would cause you to burst into flames. ;>)! 39 13!

14 Electron Transport Chain Overview 2! At the end of the chain the reduced oxygen has 2 extra electrons and so combines with 2 H + to form H 2 O (metabolic water).! The energy released by the cascading of electrons along the chain is used to pump pairs of H + from the matrix into the intermembrane space. This produces both concentration and electrical gradients that make H + s want to move back into the matrix.! On average, the energy released by electrons from NADH cause 3 pairs of H + to be pumped through the membrane. Two pairs of H + are pumped for each FADH 2.! 40 Electron Transport Chain Overview 3! H + s move across the membrane into the matrix only through special membrane channels, ATP synthase. This diffusion also releases energy ([high] [low]). The released energy is (somehow) used by ATP synthase to drive the reaction: ADP + P i ATP.! On average it takes one pair of H + s to make one ATP.! Therefore,! For each NADH + H +, 3 ATP are produced! For each FADH 2, 2 ATP are produced! 41 Oxidative Phosphorylation Figure 25-5a as shown in text! 42 14!

15 Oxidative Phosphorylation modified Figure 25-5a! High energy! 2 e -! 2 e -! FADH 2 is actually in the matrix.! 2 H +! 2 H +! Matrix! 2 H +! Intermembrane! space! Low energy! (REDOX potential) 43 Oxidative Phosphorylation Figure 25-5b! FYI: a/a 3, above, a.k.a. cytochrome oxidase is blocked by cyanide, CO, and others! 44 Energy Statement! Summary of the Energy Yield during Aerobic Metabolism of Glucose Note: 1. Energy yield is in moles of ATP. 2. Substrate level phosphorylation means that a phosphate (Pi) was transferred from one substrate to another. 3. Oxidative phosphorylation involves events occurring along the electron transport chain in the mitochondrial inner membrane. 1. From glycolysis Substrate level phosphorylation Oxidative phosphorylation NADH (in cytoplasm) X ATP/NADH 2. From pyruvate acetate step to enter Krebs cycle Oxidative phosphorylation NADH (in mitochondrion) X ATP/NADH ATP ATP ATP 3. From Krebs cycle Substrate level phosphorylation ATP Oxidative phosphorylation NADH (in mitochondrion) X ATP/NADH ATP FADH2 (in mitochondrion) X ATP/FADH2 ATP Total 36! (moles ATP/mole glucose) Your metabolic pathways assignment requires this energy statement, not Figure 25-6.! 45 15!

16 ! Chapter 25 - Metabolism! Proteins for Energy! Amino acids enter metabolism via:! 1. Pyruvate! 2. Acetyl-CoA! 3. Krebs intermediates (e.g. α-ketoglutarate)! Often requires deamination! Produces ammonia (NH 3 )! Converted in liver to urea! (less toxic)! 46 Lipids for Energy! Triglycerides glycerol + fatty acids! 1. Glycerol enters glycolysis! 2. Fatty acids undergo β-oxidation and enter as Acetyl-CoA! Liver can interconvert amino acids, fatty acids, glucose! 47 β-oxidation of Fatty Acids in Mitochondrion! Figure 25-8! Why 17?! Figure this out.! 48 16!

17 !! Chapter 25 - Metabolism! Metabolic Pathways Assignment! METABOLIC PATHWAYS EXAM, 80 POINTS See handout on website A metabolic pathway is a series of biochemical reactions that proceeds in a particular order and produces specific chemical end products. The only way to initially learn about the steps involved in a metabolic pathway is to memorize them. This is a very straightforward assignment. We will discuss why this is important and see the beauty of these metabolic pathways in lecture. Some questions we will answer are: Why do we need oxygen to survive? Why does carbon dioxide come out of your mouth when you exhale? How does cyanide kill a person? How can some animals (e.g. kangaroo rats) survive without ever drinking water? After completing this assignment, you will be familiar enough with these pathways that you can actually enjoy and appreciate this very cool subject. Use the figures in Chapter 25 (e.g. 25-3, -4b, -5b, -11 (p. 937)) in the textbook to obtain the information that you will need to ace this exam. Beginning with a blank sheet of paper you will write these five items: 1) Draw a diagram showing how one mole of glucose is completely oxidized to water and carbon dioxide during aerobic cellular respiration. Include the names of ALL substrates, coenzymes (e.g. NAD +, NADH), etc. as shown for: a) glycolysis (Figure 25-3) DO NOT include the information in the white text boxes. b) pyruvic acid acetyl-coa (First step in Figure 25-4b) c) Krebs cycle (remainder of Figure 25-4b: Indicate that Krebs cycle turns twice for each mole of glucose), and d) the electron transport chain (Figure 25-5b.) 2) Your diagram should also include the carbon skeleton structures for: a) ALL glycolytic intermediates (glucose through pyruvate) b) ALL Krebs cycle intermediates c) Use the simple cartoon chemical formulas shown in the text. You do not need to include real chemical formulas. 3) Indicate where and how the subunits of triglycerides (fatty acids and glycerol) and proteins (amino acids) can enter metabolic pathways (see Figure 25-11, p. 937). It is simplest to just add this information to the diagram you drew for #1, above. You are doing a lot of extra work if you try to draw an entirely new figure like ) Write an Energy Statement that shows many moles of ATP are generated by substrate level phosphorylation and oxidative phosphorylation in each of the following stages: a) glycolysis, b) pyruvic acid to acetyl-coa, c) Krebs cycle and d) the electron transport chain. An example of the energy statement will be available on my website. Include ALL information shown in the example. DO NOT USE Figure 25-6 in the text! I will post a handout on this that we will discuss in lecture. (If you working on this before the term has started, leave this particular part until later.) 5) Write a balanced equation for the aerobic cellular respiration of glucose. 36 ADP + 36 P i + C 6H 12O O 2 6 CO H ATP + HEAT 49 In Case You Are Curious! Why do the Figures show 1 mole of NADH (+ H + ) generated in the cytoplasm resulting in 2 moles of ATP/ mole glucose rather than 3 moles ATP/ mole glucose like those generated within the mitochondrion?! The electrons need to be passed from the cytoplasm into the mitochondrion. The toll at the border depends upon the cell type.! FYI: see next two slides.! 50 Glycerol Phosphate Shuttle FYI !

18 Malate Aspartate Shuttle Heart/Liver FYI Cytoplasm Matrix !