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Transcript
Metabolism Metabolism is all the chemical reactions that occur in an organism Nearly all the reactions in the living system are catalyzed by enzymes Metabolic pathways are a series of 2-20 enzyme catalyzed steps that direct chemical reactions Each of the participants in the chain of reactions is a metabolite Cellular respiration – food fuels are broken down within cells and some of the energy is captured to produce ATP Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Catabolism Conversion of large complex molecules into simpler, smaller ones Some of the reactions release chemical energy A portion of this energy is captured as ATP (40%) and the rest is released as heat Cells break down excess carbohydrates first, then lipids Cells conserve amino acids because anabolism require more amino acids than lipids and only few carbohydrates. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Anabolism Conversion of small molecules to larger ones in the process of biosynthesis Require chemical energy In general, biosynthesis is not a simple reversal of its pathway for catabolism Anabolism is used for: Performance of structural maintenance and repair Support of growth Production of secretions Building of nutrient reserves Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Oxidation, reduction and energy transfer • Oxidation is loss of electrons; Reduction is gain of electrons • • • oxidation can also be the loss of H and reduction is the gain of H In oxidation/reduction reactions, one chemical is oxidized, and its electrons are passed to another (reduced, then) chemical. The 2 reactions are always paired – when electrons pass from a molecule to another, the electron donor is oxidized and the electron recipient is reduced. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Oxidation, reduction and energy transfer • In a typical oxidation-reduction reaction, the reduced molecule gains energy and Oxidized substances lose energy • Not all energy is gained by the reduced molecule because some is released as heat and some is used to form ATP http://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookEnzym.html Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Cellular respiration: Coenzymes When a substance is oxidized, the liberated hydrogen atoms do not remain free but are transferred immediately by coenzyme to another compound Coenzymes act as hydrogen (or electron) acceptors Many of the metabolic processes require the removal of hydrogen - these reactions often involve a dehydrogenase enzyme Two coenzymes are commonly used to carry hydrogen atoms: Nicotinamide adenine dinucleotide (NAD) Flavin adenine dinucleotite (FAD) – a derivative of vitamin B2 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings http://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookEnzym.html ATP shuttles chemical energy within the cell In cellular respiration, some energy is stored in ATP molecules ATP powers nearly all forms of cellular work A typical cell has about a billion molecules of ATP, each last for less than a minute before it is used Rearrangement of atoms will either store or release energy chemical reaction = rearrangement of atoms Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings This reaction supplies energy for cellular work: Adenine Phosphate groups Hydrolysis Energy Ribose Adenosine triphosphate Adenosine diphosphate (ADP) Two mechanisms to “capture” energy and make ATP Substrate-level phosphorylation – phosphat groups are transferred directly from a substrate Oxidative phosphorylation – chemiosmotic process Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Mechanisms of ATP Synthesis: Substrate-Level Phosphorylation High-energy phosphate groups are transferred directly from phosphorylated substrates to ADP ATP is synthesized via substrate-level phosphorylation in glycolysis and the Krebs cycle Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 24.4a Mechanisms of ATP Synthesis: Oxidative Phosphorylation Uses the chemiosmotic process whereby the movement of substances across a membrane is coupled to chemical reactions Is carried out by the electron transport proteins in the cristae of the mitochondria Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Cellular respiration • In cellular respiration, the chemical energy in various nutrients, such as glucose, is transferred to ATP. • Cellular respiration can be divided into three metabolic processes each occurs in a specific region of the cell. • Glycolysis occurs in the cytoplasm – breakdown of glucose to pyruvic acid. • The Krebs cycle takes place in the matrix of the mitochondria. • Oxidative phosphorylation via the electron transport chain is carried out on the inner mitochondrial membrane. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Carbohydrate Metabolism Polysaccharides are hydrolyzed into monosaccharides 80% glucose Hepatocytes convert fructose and some of galactose to glucose Glucose is the preferred source for ATP production It is also used for the synthesis of amino acids, glycogen and triglycerides Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Aerobic respiration is the use of oxygen in cells. Aerobic respiration can release energy from a molecule of glucose to produce 36 ATP, shown in this equation. C6H12O6+6O2 --Enzymes---> 6CO2+6H2O+36ATP this formula gives energy for cell activities Glucose Oxygen Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Carbon dioxide Water Energy Glycolysis (anaerobic metabolism) Glycolysis breaks a six-carbon glucose into two three-carbon molecules - two molecules of pyruvic acid that moves to the Krebs cycle Glycolysis consume 2 ATP molecules but produces 4 ATP molecules – net gain of 2 ATP During the first half of the process ATP is “invested” to split the glucose The second half of the process the pyruvate is formed and ATP is generated During the process 2 molecules of NAD+ are reduced to form 2 NADH and 2H+ (NAD+ is the oxidized form – less energy and NADH is the reduced form – more energy) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 1st half – ATP “invested” 2nd half – ATP generated 2 Pyruvic acid Glucose Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The 2 ATP molecules that were generated during glycolysis represent only 3% of the energy that is contained in the glucose molecule The pyruvic acid contain 90% of the energy that was originally in the glucose molecule The subsequent process of breaking down the pyruvate is aimed to release this energy The fate of pyruvic acid depends on the availability of oxygen: In an anaerobic environment (no oxygen) it will be converted into lactic acid. Lactic acid diffuses out of the cells, arrives via bloodstream to the liver where it is converted back into pyruvic acid In aerobic environment, pyruvic acid will enter the Krebs cycle Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The tricarboxylic acid (TCA)/citric acid/Krebs cycle The significance of the TCA cycle is that it takes the 3-carbon leftover from glycolysis (pyruvic acid) and breaks it down in such a way as to yield a large amount of useable energy. The pyruvic acid has three carbons. Before it enters the TCA cycle, it is reduced to two carbons as acetate attached to coenzyme-A (CoA). The combination is called acetyl-CoA. During this process 1 molecule of CO2 and 2 of NADH are released CoA 2 Pyruvic acid Acetic acid 1 CO2 3 Coenzyme A Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Acetyl-CoA (acetyl-coenzyme A) The tricarboxylic acid (TCA)/citric acid/Krebs cycle Acetyl CoA (2 carbons) is attached to a 4-carbon oxaloacetic acid molecule to form a 6-carbon citric acid. The CoA is released intact and can bind another acetyl group The citric acid is converted to a 4-carbon molecule releasing 2 molecules of CO2 and hydrogen atoms that are removed by NAD (transform to NADH) Than the 4-carbon molecule is being transformed and by that releasing CO2 and H2O The main goal of this process is to transfer energy from the pyruvic acid to coenzymes Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Krebs Cycle An eight-step cycle in which each acetic acid is decarboxylated and oxidized, generating: Three molecules of NADH + H+ One molecule of FADH2 Two molecules of CO2 One molecule of ATP For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Input Output 2 1 Acetic acid 2 CO2 ADP 3 Krebs Cycle 3 NAD 4 FAD 5 6 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6.11 Oxidative phosphorylation / Electron transfer system Requires coenzymes and consumes oxygen Key reactions take place in the electron transport system (ETS) The basic chemical reaction is: 2 H2 + O2 2 H2O Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Oxidative phosphorilation Each carrier in the chain is reduced as it picks up electron and than oxidized as it gives it up The electron transfer release energy that is used to form ATP Energy from the NADH is used to pump H+ from the matrix of the mitochondria into the intermembrane space (proton pump) That results in high H+ concentration in the intermembrane space These are moved through special channels and the movement results in energy release that is used to form ATP Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Electronic Energy Gradient The transfer of energy from NADH + H+ and FADH2 to oxygen releases large amounts of energy This energy is released in a stepwise manner through the electron transport chain The electrochemical proton gradient across the inner membrane: Creates a pH gradient Generates a voltage gradient These gradients cause H+ to flow back into the matrix via ATP synthase Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Summary of ATP Production Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 24.11 Glycogenesis and Glycogenolysis Glycogenesis – formation of glycogen when glucose supplies exceed cellular need for ATP synthesis Glycogenolysis – breakdown of glycogen in response to low blood glucose Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 24.12 Lipid Metabolism - classes of lipids in the human body Triglycerides main storage form of metabolic fuel (9 kcal/g). Can supply weeks or months of starvation (stored carbohydrates can supply about a day) This molecule is composed of three molecules of fatty acid (which may all be the same or all different) attached to a glycerol molecule. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings phospholipids Phospholipids have only two molecules of fatty acid attached to glycerol with the third hydroxyl group on glycerol bonded to a phosphate and then to a polar alcohol group. This gives the molecule the structure with a polar "head" (the phosphate and alcohol) and a long non-polar "tail", the latter contributed by the fatty acid molecules. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Steroids Steroids DO NOT contain fatty acids. They contain a mostly hydrocarbon structure, but instead of being linear like fatty acids, they are composed of ring structures. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Fatty acids Fatty acids consist of a long hydrocarbon chain with a terminal carboxyl group. The hydrocarbon chain commonly contains 15-20 carbons. This type of structure is highly non-polar and hence water insoluble. stearic acid palmitic acid oleic acid Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lipid catabolism - lipolysis Lipids broken down into pieces that can be converted into pyruvate Triglycerides are split into glycerol and 3 fatty acids Glycerol enters TCA cycle after being broken to pyruvic acid in the cytosol. Fatty acids enter the mitochondrion Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Fatty acid activation • Fatty acids must be activated before they can be carried into the mitochondria, where fatty acid oxidation occurs. • Once activated, the fatty acyl CoA is transported into the mitochondrial matrix. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lipid catabolism - lipolysis Long chain fatty acyl CoA is degraded by Beta-oxidation. The products of beta-oxidation are: acetyl CoA FADH2, NADH and H+ Fate of acetyl CoA Oxidation by the Krebs cycle to CO2 and H2O. In liver only, acetyl CoA may be used for ketone body synthesis. Fate of the FADH2 and NADH + H+ FADH2 and NADH + H+ are oxidized by the mitochondrial electron transport system, yielding ATP. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lipids and energy production Lipids are stored as droplets in the cytoplasm which make them more difficult to access than carbohydrate reserves Lipids are processed in the mitochondria and the mitochondrial activity is limited by the availability of oxygen As a result, lipids cannot provide large amounts in ATP in a short amount of time Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lipid synthesis (lipogenesis) Almost any organic molecule can be used to form glycerol Essential fatty acids cannot be synthesized and must be included in diet Linoleic and linolenic acid come from plants They are used for prostaglandins and some phospholipids production Lipogenesis occur in the liver and adipose tissue Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings ketogenesis Ketogenesis occurs in the mitochondrial matrix in the liver When carbohydrate intake is inadequate the body starts to break down lipids. Ketone bodies are produced when: fasting or starvation conditions or after a meal rich in triglycerides not enough insulin in the blood Breaking lipids will result in excess acetyl CoA The ability of acetyl CoA to enter the Krebs cycle is limited The result is accumulation of acetyl CoA The acetyl CoA is then used in ketogenesis (synthesis of keton bodies/ketones) Ketone bodies are produced in small quantities in healthy persons. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Low CHO intake, insufficient insulin Fatty acids flood the liver Acetyl-CoA Many Acetyl-CoA Limited Acetyl-CoA Ketone Citric Acid Bodies Cycle Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lipid transport and distribution Lipids are hydrophobic molecules that need to be transported carried by proteins Lipoproteins are lipid-protein complexes. Each type has a different function, but all are transport “vehicles” The superficial coating of phodpholipids and proteins make the complexes soluble Proteins in the outer shell are called apoproteins The inner core is built out of lipids Lipoprotein are categorized by their density which results from the ratios between lipids (low density) and proteins (high density) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lipoproteins types General categories of lipoproteins, listed in order from larger and less dense (more fat than protein) to smaller and more dense (more protein, less fat): Chylomicrons carry ingested triglycerides (fat) from the intestine to the liver and to adipose tissue for storage. Enter lacteals and carried by lymph into systemic circulation. Lipoprotein lipase - enzyme that breaks down complex lipids because the chylomicrons are too big to diffuse across capillary walls Found in capillary walls of liver, adipose tissue, skeletal and cardiac muscle Releases fatty acids and monoglycerides that diffuse to interstitial fluids Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings •Retrieved from "http://en.wikipedia.org/wiki/Lipoprotein" Lipid Transport and Utilization Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 25.11a Lipoproteins types - Very Low Density lipoproteins (VLDL) form by the hepatocytes carry newly synthesized triglycerides from the liver to adipose tissue for storage After depositing some of their triglycerides they are converted to LDLs Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lipoproteins types - Low Density Lipoproteins (LDL) carry 75% of cholesterol from the liver to cells of the body. LDL enters the cells where it is being broken down to release cholesterol when a cell has sufficient cholesterol it will prevent by negative feedback the entrance of LDL into it When present in excessive amount, LDL deposit cholesterol in and around smooth muscle fibers in the arteries (that is why sometimes it is referred to as the "bad cholesterol" lipoprotein). Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lipoproteins types - High Density Lipoproteins (HDL) collects cholesterol from the body's tissues and brings it back to the liver. Sometimes referred to as the "good cholesterol" lipoprotein Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Protein metabolism Body can synthesize 100,000-140,000 different proteins Each protein contain a combination of the same 20 amino acids Cellular proteins are continuously recycled in the cytoplasm Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Protein Metabolism Excess dietary protein results in amino acids being: Oxidized for energy Converted into fat for storage Amino acids must be deaminated prior to oxidation for energy Deaminated amino acids are converted into: Pyruvic acid One of the keto acid intermediates of the Krebs cycle These events occur as transamination, deamination, and keto acid modification Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings oxidative Oxidation of Amino Acids Transamination – switching of an amine group from an amino acid to a keto acid (usually -ketoglutaric acid of the Krebs cycle) Typically, glutamic acid is formed in this process Oxidative deamination – the amine group of glutamic acid is: Released as ammonia Combined with carbon dioxide in the liver Excreted as urea by the kidneys Keto acid modification – keto acids from transamination are altered to produce metabolites that can enter the Krebs cycle Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Synthesis of Proteins Amino acids are the most important anabolic nutrients, and they form: All protein structures The bulk of the body’s functional molecules A complete set of amino acids is necessary for protein synthesis All essential amino acids must be provided in the diet Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings