Cell Metabolism

BIG PICTURE BIG PICTURE The sun provides the energy that powers all life The sun provides the energy that powers all life Animals depend on plants to convert solar energy to chemical energy Animals depend on plants to convert solar energy to chemical energy This chemical energy is in the form of organic molecules This chemical energy is in the form of organic molecules

Cellular Respiration The main way that chemical energy is harvested from organic molecules and converted to ATP The main way that chemical energy is harvested from organic molecules and converted to ATP Series of catabolic reactions Series of catabolic reactions This is an aerobic process —it requires oxygen This is an aerobic process —it requires oxygen OVERALL EQUATION OVERALL EQUATION GlucoseOxygen WaterEnergy Carbon Dioxide

Oxidation-Reduction Reactions Reactions transferring electrons from one molecule to another Reactions transferring electrons from one molecule to another Molecules that lose electrons are said to be oxidized Molecules that lose electrons are said to be oxidized Molecules that gain electrons are said to be reduced Molecules that gain electrons are said to be reduced Movement of electrons is usually associated with movement of hydrogen atoms Movement of electrons is usually associated with movement of hydrogen atoms

Glucose OxygenWaterEnergy Carbon Dioxide Which molecule is oxidized and which is reduced during cellular respiration?

Oxidation Reduction Oxygen gains electrons (and hydrogen] Glucose loses electrons (and hydrogen)

Enzymes Involved Dehydrogenases - enzymes that catalyze redox reactions by removing hydrogen Dehydrogenases - enzymes that catalyze redox reactions by removing hydrogen Most require coenzymes that are able to accept and carry the electrons (electron carriers) Most require coenzymes that are able to accept and carry the electrons (electron carriers) Nicotinamide adenine dinucleotide (NAD+) – derived from niacin Nicotinamide adenine dinucleotide (NAD+) – derived from niacin Flavin adenine dinucleotide (FAD) – derived from riboflavin Flavin adenine dinucleotide (FAD) – derived from riboflavin

Electron Carriers

NAD+ FAD Electron Carriers

Stages of cellular respiration

Mechanisms of ATP Synthesis Substrate-level phosphorylation Substrate-level phosphorylation Enzymes transfer a phosphate group from a substrate to ADP Enzymes transfer a phosphate group from a substrate to ADP Occurs during glycolysis and Krebs cycle Occurs during glycolysis and Krebs cycle

Mechanisms of ATP Synthesis Oxidative phosphorylation Oxidative phosphorylation The phosphorylation of ADP is powered by a series of redox reactions that transfer electrons from organic molecules to oxygen The phosphorylation of ADP is powered by a series of redox reactions that transfer electrons from organic molecules to oxygen Produces the majority of the ATP molecules Produces the majority of the ATP molecules In electron transport system In electron transport system

Stage 1: GLYCOLYSIS Occurs in the cytoplasm Occurs in the cytoplasm Does not require oxygen (anaerobic) Does not require oxygen (anaerobic) Six carbon glucose molecule is broken down into 2 three carbon molecules of pyruvic acid Six carbon glucose molecule is broken down into 2 three carbon molecules of pyruvic acid Produces 2 net ATP and 2 NADH (electron carrier) Produces 2 net ATP and 2 NADH (electron carrier)

INVESTMENT STAGE

PAYOFF STAGEPAYOFF STAGE

Stage 1: GLYCOLYSIS

The Fate of Pyruvic Acid Depends on the availability of oxygen Depends on the availability of oxygen In aerobic conditions pyruvic acid is converted to acetyl-CoA and enters the Krebs cycle In aerobic conditions pyruvic acid is converted to acetyl-CoA and enters the Krebs cycle In anaerobic conditions NADH + H + reduces pyruvic acid to form lactic acid In anaerobic conditions NADH + H + reduces pyruvic acid to form lactic acid

Lactic Acid Fermentation Produces 2 ATP per glucose (less efficient) Produces 2 ATP per glucose (less efficient) When oxygen becomes available again lactic acid is oxidized back to pyruvic acid and enters the Krebs cycle. When oxygen becomes available again lactic acid is oxidized back to pyruvic acid and enters the Krebs cycle.

Stage 1½ : TRANSITION Pyruvic acid enters the mitochondrial matrix through facilitated diffusion Pyruvic acid enters the mitochondrial matrix through facilitated diffusion There it is converted to Acetyl-Coenzyme A to enter Krebs cycle There it is converted to Acetyl-Coenzyme A to enter Krebs cycle 1 CO 2 and 1 NADH is produced in this stage per pyruvate 1 CO 2 and 1 NADH is produced in this stage per pyruvate

Stage 2: KREBS CYCLE Occurs in the matrix of the mitochondria Occurs in the matrix of the mitochondria Requires oxygen (aerobic) Requires oxygen (aerobic) Completes the breakdown of glucose to CO 2 and harvests the energy as: Completes the breakdown of glucose to CO 2 and harvests the energy as: 2 ATP 2 ATP 6 NADH 6 NADH 2 FADH 2 2 FADH 2 4 CO 2 (per 1 glucose) Oxaloacetic acid Citric acid Two of these cycles per 1 glucose molecule

Stage 2: KREBS CYCLE Acetate joins the 4 carbon compound oxaloacetate to form the 6 carbon compound citrate Acetate joins the 4 carbon compound oxaloacetate to form the 6 carbon compound citrate 2 decarboxylation events release 2 CO 2 2 decarboxylation events release 2 CO 2

Stage 2: KREBS CYCLE Four oxidation events generate 3 NADH and 1 FADH 2 Four oxidation events generate 3 NADH and 1 FADH 2 1 molecule of ATP is formed via substrate-level phosphorylation 1 molecule of ATP is formed via substrate-level phosphorylation Note these numbers are per cycle. For each glucose molecule you have two cycles. Note these numbers are per cycle. For each glucose molecule you have two cycles.

Stage 3: Electron Transport Chain The hydrogen being delivered to the ETC by the coenzymes are split into electrons and H+ ions The hydrogen being delivered to the ETC by the coenzymes are split into electrons and H+ ions Electrons from NADH and FADH 2 are passed down a chain of protein complexes embedded in the inner membrane of the mitochondria Electrons from NADH and FADH 2 are passed down a chain of protein complexes embedded in the inner membrane of the mitochondria

Electrons fall to lower energy levels as they are passed down the chain (releases energy) Electrons fall to lower energy levels as they are passed down the chain (releases energy) Oxygen is the final electron acceptor Oxygen is the final electron acceptor The negative oxygen binds to 2 H+ to form water The negative oxygen binds to 2 H+ to form water Stage 3: Electron Transport Chain

Chemiosmosis Chemiosmosis The energy released by electrons moving down the chain is used to pump H+ from the matrix to the intermembrane space The energy released by electrons moving down the chain is used to pump H+ from the matrix to the intermembrane space This creates a proton gradient (potential energy) This creates a proton gradient (potential energy)

Stage 3: Electron Transport Chain This gradient drives protons back in through a protein called ATPsynthase This gradient drives protons back in through a protein called ATPsynthase This creates kinetic energy that ATPsynthase harnesses to catalyze This creates kinetic energy that ATPsynthase harnesses to catalyze ADP + P  ATP ADP + P  ATP(oxidative-phosphorylation)

Summary of ETC

Metabolic pool concept: any organic molecule can be used in respiration

Lipid Metabolism Lipolysis – the hydrolysis of triglycerides into glycerol and fatty acids Lipolysis – the hydrolysis of triglycerides into glycerol and fatty acids Catalyzed by the enzyme lipase Catalyzed by the enzyme lipase

Lipid Metabolism The glycerol The glycerol is converted into glyceraldehyde phosphate a glycolysis intermediate is converted into glyceraldehyde phosphate a glycolysis intermediate Which then enters into Krebs cycle Which then enters into Krebs cycle Complete oxidation of glycerol yields 18 ATP molecules Complete oxidation of glycerol yields 18 ATP molecules

Lipid Metabolism The fatty acid chains The fatty acid chains Are broken apart into 2 carbon acetic acid fragments (Beta-oxidation) Are broken apart into 2 carbon acetic acid fragments (Beta-oxidation) Coenzyme A is attached to the acetic acid fragments forming Acetyl CoA Coenzyme A is attached to the acetic acid fragments forming Acetyl CoA Enters the Krebs cycle Enters the Krebs cycle Complete oxidation yields ~54 ATP Complete oxidation yields ~54 ATP

Ketogenesis If Acetyl CoA production exceeds the capacity of the Krebs cycle to process it, the liver will convert it to ketone bodies which are released into the blood If Acetyl CoA production exceeds the capacity of the Krebs cycle to process it, the liver will convert it to ketone bodies which are released into the blood Ketones can be used as an energy source in skeletal and cardiac muscle Ketones can be used as an energy source in skeletal and cardiac muscle Examples of ketones: acetoacetic acid, B- hydroxybutyric acid, acetone Examples of ketones: acetoacetic acid, B- hydroxybutyric acid, acetone

Ketosis Ketosis - an increase in circulating ketone bodies Ketosis - an increase in circulating ketone bodies Occurs when lipids are the primary energy source (starvation and diabetes mellitus) Occurs when lipids are the primary energy source (starvation and diabetes mellitus) May lead to ketoacidosis – decreased blood pH May lead to ketoacidosis – decreased blood pH Depresses nervous system, may become comatose Depresses nervous system, may become comatose Compensatory response: Increased ventilation and large amounts of ketones excreted in urine Compensatory response: Increased ventilation and large amounts of ketones excreted in urine

Protein Metabolism Proteins are hydrolyzed into individual amino acids by proteases Proteins are hydrolyzed into individual amino acids by proteases Amino acids are deaminated in the liver (amine group is removed) Amino acids are deaminated in the liver (amine group is removed) Amine group is removed as ammonia Amine group is removed as ammonia Combined with CO 2 to form urea which is excreted by the kidneys Combined with CO 2 to form urea which is excreted by the kidneys

Protein Metabolism: Deamination Also generates organic acids which can be converted to glucose or enter Krebs cycle to be oxidized for energy Also generates organic acids which can be converted to glucose or enter Krebs cycle to be oxidized for energy

Protein Metabolism

Glucose Synthesis Aerobic metabolism of glucose is the most efficient way for cells to make ATP Aerobic metabolism of glucose is the most efficient way for cells to make ATP It is the primary source of energy in cells and normally the ONLY source in neurons It is the primary source of energy in cells and normally the ONLY source in neurons There is multiple metabolic pathways for producing glucose to ensure that there is a continuous supply for the brain There is multiple metabolic pathways for producing glucose to ensure that there is a continuous supply for the brain

Synthesis of Glucose Glycogenolysis – the breakdown of glycogen to glucose Glycogenolysis – the breakdown of glycogen to glucose The liver and skeletal muscle contains high concentrations of glycogen The liver and skeletal muscle contains high concentrations of glycogen

Synthesis of Glucose Gluconeogenesis - synthesis of glucose from non-carbohydrates Gluconeogenesis - synthesis of glucose from non-carbohydrates Can start with glycerol, lactic acid or various amino acids Can start with glycerol, lactic acid or various amino acids Occurs in the liver and kidneys Occurs in the liver and kidneys