Metabolic Reactions and Energy Transfer Learning Outcome 26: Define metabolism.

Metabolism The sum of catabolism and anabolism Catabolism - decomposition reactions that break down molecules and release energy. Heat, light, sound Anabolism - synthesis reactions that build molecules and require energy. Make chemical bonds DNA

Metabolic Reactions Learning Outcome: 27: Explain the role of ATP in anabolism and catabolism.

Coupling of Catabolism and Anabolism by ATP ATP couples energy-releasing reactions to energy- requiring reactions. Catabolism - some of the energy (approx. 40%) is transferred to ATP; the rest is given off as heat. Anabolism - ATP provides the energy for synthesis; some energy is given off as heat.

Figure 25.1 Role of ATP in linking anabolic and catabolic reactions.

Energy Transfer Learning Outcome 28: Describe oxidation- reduction reactions.

Oxidation – Reduction Reactions Oxidation (OIL) The removal of electrons from a molecule. Results in a decrease in the energy content of the molecule. Most biological examples are dehydrogenation reactions. Ex: Lactic acid  Pyruvic acid + 2H 2H is in the form H+ + H- Dehydrogenation – loss of hydrogen atoms 2 neutral hydrogen atoms are removed as one hydrogen ion (H+) and one hydride ion (H-) Page 942 in textbook

Oxidation – Reduction Reactions Reduction (RIG) The addition of electrons to a molecule. It results in an increase in the energy content of the molecule. Example: Pyruvic acid + 2H  Lactic acid. LDH = lactate dehydrogenase NADH is a coenzyme found in all living cells. It stands for nicotinamide adenine dinucleotide hydride. It is a dinucleotide (2 nucleotides joined through their phosphate groups) Coenzyme = enhances the work of enzymes in the body The H stands for the high energy hydrogen  meaning it is a biologically active state When the body is deficient in NADH, it is kind of like a car that has run out of gasoline.  The production of NADH declines as we age

Lactic Acid Cycle Lactic acid diffuses from the muscles and is transported through the bloodstream to oxygen-rich tissues such as the heart and liver, where it is catabolized further through the lactic acid cycle or converted to glucose via gluconeogenesis. Even in fully oxygenated muscle tissue, as much as 50% of the metabolized glucose is converted to lactic acid by way of pyruvic acid If you exercise strenuously without sufficient oxygen, lactic acid accumulates and contributes to muscle fatigue and soreness. When oxygen is later available, lactic acid must be oxidized to pyruvic acid.

Oxidation – Reduction Reactions Oxidation and reduction reactions are always coupled. Such paired reactions are called redox reactions. Oxidation reactions are usually exergonic. Aided by coenzymes Oxidation is loss Reduction is gain

Redox Coenzymes When a substance is oxidized, the 2H atoms released are used to reduce another substance. Two coenzymes that carry 2H atoms from an oxidation reaction to a reduction reaction are: Nicotinamide adenine dinucleotide (NAD) Flavin adenine dinucleotide (FAD) NAD is derived from vitamin B (niacin) FAD is derived from vitamin B2 (riboflavin)

NAD Reduction Malic Acid Oxaloacetic Acid H+ + H- NAD+ NADH + H+ reduced oxidized NADH is a coenzyme found in all living cells. It stands for nicotinamide adenine dinucleotide hydride. It is a dinucleotide (2 nucleotides joined through their phosphate groups) Coenzyme = enhances the work of enzymes in the body The H stands for the high energy hydrogen  meaning it is a biologically active state When the body is deficient in NADH, it is kind of like a car that has run out of gasoline.  The production of NADH declines as we age The addition of a hydride ion neutralizes the charge

NADH + H+ Oxidation Pyruvic Acid Lactic Acid H+ + H- NAD+ NADH + H+ reduced H+ + H- NAD+ NADH + H+ oxidized

FAD Reduction Succinic Acid Fumaric Acid H+ + H- FAD FADH2 oxidized reduced oxidized

FADH2 Oxidation Fumaric Acid Succinic Acid H+ + H- FAD FADH2 oxidized reduced H+ + H- FAD FADH2 oxidized

Energy Transfer Learning Outcome 29: Describe three mechanisms of ATP generation.

Three Mechanisms of ATP Generation Substrate-level phosphorylation Generate ATP directly by transferring a phosphate group to ADP. Oxidative phosphorylation Generate ATP indirectly by transporting electrons from oxidized substances to the electron transport chain. Photophosphorylation Generate ATP from light energy.

Carbohydrate Metabolism Learning Outcome 30: Describe the mechanism of glucose movement into body cells.

Glucose Movement into Cells In digestive tract, polysaccharides  monosaccharides. 80% glucose, 20% fructose and galactose Absorption through epithelial cells of the intestine converts some fructose into glucose Absorbed monosaccharides are transported to the liver Liver hepatocytes convert other monosaccharides to glucose. So…carbohydrate metabolism = glucose metabolism

Glucose Movement into Cells Glucose must pass PM into cytosol before cells can use it. Absorption via Na+ - glucose symporters Insulin Dependent GluT molecules Secondary active transport In GI tract and kidneys Family of facilitated diffusion transporters Most other body cells

Glucose Movement into Cells Normal blood glucose = 90 mg/100 ml of plasma. Controlled by negative feedback Approx 2-3g of glucose circulates in your blood

Carbohydrate Metabolism Learning Outcome 31: Describe glucose catabolism.

Fates of Glucose ATP production Amino acid synthesis When body cells need immediate energy glucose is oxidized  ATP Amino acid synthesis Glucose can be used to form a.a. and then proteins Glycogen synthesis Hepatocytes and muscle fibers = glycogenesis Formation of glycogen (hundreds of glucose monomers) Triglyceride synthesis When glycogen stores are filled Hepatocytes convert glucose  glycerol and fatty acids for lipogenesis Triglycerides stored in adipose tissue

Glucose Catabolism AKA cellular respiration. Provides the cell’s chief source of energy. Occurs in four successive stages: Glycolysis Formation of acetyl coenzyme A The Krebs cycle The electron transport chain heat 36 or 38 ATP C6H12O6 + 6O2 6H2O + 6CO2

Oxidation of Glucose heat 36 or 38 ATP C6H12O6 + 6O2 6H2O + 6CO2

Figure 25.2 Overview of cellular respiration (oxidation of glucose).

Glycolysis The first stage of glucose catabolism. Occurs in the cytosol Does not require oxygen (anaerobic reaction). Converts 1 glucose (6 carbons) into two pyruvic acid (3 carbons each). Energy molecules produced: 2 ATP 2 NADH

Figure 25.3 Cellular respiration begins with glycolysis

Figure 25.4 The 10 reactions of glycolysis

Summary of Glycolysis Where does this happen? What are the reactants? Cytosol What are the reactants? Glucose What are the products? 2 (3C) pyruvic acids How much $? 2 ATP 2 NADH

The Fate of Pyruvic Acid Dependent on oxygen availability: When oxygen is in short supply, pyruvic acid is reduced to lactic acid. Ex. During strenuous exercise in skeletal muscle fibers – build up causes muscle fatigue. When oxygen is plentiful, most cells convert pyruvic acid to acetyl coenzyme A.

Oxygen Requirements Summary Glycolysis has no O2 requirement – aerobic or anaerobic conditions Aerobic respiration is Krebs cycle and electron transport chain – both require O2 All 4 stages of glucose catabolism only occur when O2 is present When there is little to no O2 then pyruvic acid is converted into lactic acid and cellular respiration halts.

Figure 25.5 Fate of pyruvic acid Because RBC lack mitochondria, they can only produce ATP through glycolysis

Formation of Acetyl Coenzyme A Each step in oxidation of glucose requires a different enzyme and often coenzyme Acetyl Coenzyme A connects glycolysis (cytosol) to Krebs cycle (mitochondria)

Formation of Acetyl Coenzyme A Occurs in the mitochondrial matrix Pyruvic acid (3C)  acetyl group (2C). The carbon is lost as CO2 (decarboxylation). Coenzyme A is added to the acetyl group to form acetyl CoA NAD+ is reduced to NADH

Figure 25.5 Summary of Acetyl CoA Formation Reactants: 2 pyruvic acids 2 coenzyme A Products 2 acetyl CoA 2 CO2 2NADH

Krebs Cycle Also called the citric acid cycle First molecule formed when an acetyl group joins Step-by-step release of energy stored in acetyl CoA Involves decarboxylations and redox reactions Occurs in the mitochondrial matrix Each time an acetyl CoA enters the cycle, it undergoes one complete “turn” Starts by forming citric acid and ends by forming oxaloacetic acid

Figure 25.6 After formation of acetyl coenzyme A...

Krebs Cycle Each time an acetyl CoA enters the cycle, it undergoes one complete “turn” Starts by forming citric acid and ends by forming oxaloacetic acid Products for each turn: 3 NADH 3 H+ 1 FADH2 1 ATP – substrate-level phosphorylation 2 CO2 – decarboxylation Each glucose molec provides 2 acetyl CoA = 2 turns redox reactions

Figure 25.7 The eight reactions of the Kreb’s cycle. Summary of Kreb’s Cycle Reactants: 2 acetyl CoA Products 4 CO2 2 ATP 6 NADH 2 FADH2

The Electron Transport Chain A sequence of electron carrier molecules Integral membrane proteins On the inner mitochondrial membrane (cristae) Capable of a series of redox reactions The last electron receptor of the chain is O2 Energy stored in NADH and FADH2 is used to pump H+ from the matrix into the space between the inner and outer membranes.

Chemiosmosis produces ATP Links chemical reactions with pumping H ions. H+ ions are allowed to diffuse back into the matrix (chemiosmosis) H+ channels are coupled with ATP synthase 1 NADH  3 ATP molecules 1 FADH2  2 ATP molecules

Figure 25.8 Chemiosmosis

Figure 25.9 Electron Transport Chain Details Each pump = complex of 3+ electron carriers

Summary of Aerobic Cellular Respiration The complete oxidation of one glucose molecule can be represented as follows: C6H12O6 + 6O2  36 or 38ATP + 6CO2 +6H2O

Figure 25.10 Summary of Cellular Respiration

Summary of Glucose Oxidation Glycolysis 2 pyruvic acids 2 ATP (substrate-level phosphorylation) 2 NADH + 2 H+ 6 ATP (electron transport chain) Acetyl Co A synthesis 2 NADH + 2H+ Krebs Cycle 2 GTP 6 NADH + 6 H+ 18 ATP (electron transport chain) 2 FADH2 4 ATP (electron transport chain) Total 38 ATP (theoretical maximum); probably closer to 36 ATP

Assigned Reading Outcomes 7-10 Pages 8-11 in notes Focus on understanding the bolded terms (I encourage you to highlight them in NOTES) Know the definitions not the cycles Know which type of metabolism they fall under Ex. Glycogenesis, glycogenolysis, gluconeogenesis, lipoproteins, chylomicrons, VLDLs, LDLs, HDLs, lipolysis, beta oxidation, lipogenesis