1. Metabolism

2. Do We Have Enough Energy? Nutrients and regulation of appetite Carbohydrate metabolism Lipid and protein metabolism Metabolic states

3. Nutritious and Delicious Nutrient – An ingested chemical that is used for growth, repair, and maintenance of the body – Two categories Macronutrients – Must consume in large quantities – Water, carbohydrates, lipids, and proteins Micronutrients – Small quantities needed – Minerals and vitamins Calories – Kcal – Measure of the capacity to do work

4. Regulation of Appetite Short-term regulators – Ghrelin – produces sensation of hunger – Peptide YY (PYY) – sensation of satisfaction – CCK – sensory stimulus of vagus nerve (suppressor) Long-term regulators (adiposity signals) – Leptin – Insulin Arcuate nucleus of hypothalamus – NPY - stimulator – Melanocortin - suppressor

5. Carbohydrate Metabolism dietary carbohydrate burned as fuel within hours of absorption all oxidative carbohydrate consumption is essentially a matter of glucose catabolism C 6 H 12 O 6 + 6O 2  6CO 2 + 6H 2 O function of this reaction is to transfers energy from glucose to ATP – not to produce carbon dioxide and water

6. Glucose Catabolism Glucose catabolism – a series of small steps, controlled by separate enzymes, in which energy is released in small manageable amounts, as much possible transferred to ATP and the rest is released as heat Three major pathways of glucose catabolism – Glycolysis glucose (6C) split into 2 pyruvic acid molecules (3C) – Anaerobic fermentation occurs in the absence of oxygen reduces pyruvic acid to lactic acid – Aerobic respiration occurs in the presence of oxygen completely oxidizes pyruvic acid to CO 2 and H 2 O

7. Coenzymes Enzymes remove electrons (as hydrogen atoms) from intermediate compounds of these pathways and transfer to coenzymes Enzymes of glucose catabolism cannot function without their coenzymes Two coenzymes of special importance to glucose catabolism – NAD + (nicotinamide adenine dinucleotide) derived from niacin (B vitamin) NAD + + 2 H  NADH + H + – FAD (flavin adenine dinucleotide) derived from riboflavin FAD + 2 H  FADH 2

8. Overview of ATP Production Figure 26.3 Glucose Glucose 6-phosphate Glycogen Fat Fructose 6-phosphate Fructose 1,6-diphosphate 2 PGAL 2 2 NAD + 2 NADH + 2 H + 2 2 H2O 2 2 2 pyruvic acid 2 NADH + 2 H + 2 NAD + O2 lacking O2 present 2 2 lactic acid 2 2 Aerobic respirationAnaerobic fermentation 5 Dephosphorylation 1 Phosphorylation 2 Priming 3 Cleavage 4 Oxidation Pi ATP 2 ADP 2 Key Carbon atoms Phosphate groups Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. End-products of glycolysis are: 2 pyruvic acid + 2 NADH + 2 ATP + 2 H +

9. Aerobic Respiration Most ATP generated in mitochondria – Oxygen required as final electron acceptor Pyruvate decarboxylated – Combines with coenzyme A to enter matrix Occurs in two principal steps: – Matrix reactions – controlling enzymes are in the fluid of the mitochondrial matrix – Membrane reactions - controlling enzymes are bound to the membranes of the mitochondrial cristae

10. Mitochondrial Matrix Reactions Figure 26.4 10 7 6 Pyruvic acid (C3) CO2 NAD + NADH + H + Acetyl group (C2) Acetyl-Co A Coenzyme A H2O Citric acid (C6) Oxaloacetic acid (C4) H2O (C6) CO2 FAD FADH2 H2O NADH + H + NAD + 11 14 15 17 18 GTPGDP 12 13 16 Occurs in mitochondrial matrix ADP 9 8 Pi Citric acid cycle H2O NAD + NADH + H + (C4) (C5) NAD + NADH + H + CO2 (C4) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ATP

11. Summary of Matrix Reactions 2 pyruvate + 6H 2 O  6CO 2 2 ADP + 2 P i  2 ATP 8 NAD + + 8 H 2  8 NADH + 8 H + (2 NADH produced during glycolysis) 2 FAD + 2 H 2  2 FADH 2 Carbon atoms of glucose have all been carried away as CO 2 and exhaled Energy lost as heat, stored in 2 ATP, 8 reduced NADH, 2 FADH 2 molecules of the matrix reactions and 2 NADH from glycolysis Citric acid cycle is a source of substances for synthesis of fats and nonessential amino acids

12. Membrane Reactions Membrane reactions have two purposes: – to further oxidize NADH and FADH 2 and transfer their energy to ATP – to regenerate NAD + and FAD and make them available again to earlier reaction steps Mitochondrial electron-transport chain – series of compounds that carry out this series of membrane reactions

13. Members of the Transport Chain Flavin mononucleotide (FMN) – derivative of riboflavin similar to FAD – bound to a membrane protein FMN accepts electrons from NADH Iron-sulfur (Fe-S) centers – complexes of iron and sulfur atoms bound to membrane proteins Coenzyme Q (CoQ) – accepts electrons from FADH 2 – small mobile molecule that moves about in the membrane Copper (Cu) ions – bound to two membrane proteins Cytochromes – five enzymes with iron cofactors – brightly colored in pure form – in order of participation in the chain, b, c 1, c, a, a 3

14. Electron Transport hydrogen atoms are spilt apart as they transfer from coenzymes to the chain protons pumped into the intermembrane space electrons travel in pairs (2 e - ) along the transport chain each electron carrier becomes reduced when it receives an electron pair and oxidized again when it passes the electrons along to the next carrier oxygen is the final electron acceptor – each oxygen atom accepts two electrons from cytochrome a 3 and two protons from the mitochondrial matrix forming water body’s primary source of metabolic water – water synthesized in the body – this reaction explains the body’s oxygen requirement – no oxygen, cell produces too little ATP to sustain life

15. 50 40 30 20 10 Enzyme complex 1 Relative free energy (kcal/mole) 0 NADH + H + NAD + FADH2 FAD Enzyme complex 2 Reaction progress Enzyme complex 3 ½ O2 + 2 H + H2O 1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Electron Transport Chain Figure 26.5

16. Chemiosmotic Mechanism electron transport chain energy fuels respiratory enzyme complexes – pump protons from matrix into space between inner and outer mitochondrial membranes – creates steep electrochemical gradient for H + across inner mitochondrial membrane inner membrane is permeable to H + at channel proteins called ATP synthase chemiosmotic mechanism - H + current rushing back through these ATP synthase channels drives ATP synthesis

17. Chemiosmotic ATP Synthesis Figure 26.6 Matrix Inner membrane NADH + H + NAD + 2 H + H2O 3 ADP + 3 Pi 6 H + 2e – Matrix Cristae Outer membrane CoQ Cyt c ATP synthase 2 3 Enzyme complex 1 Intermembrane space Inner membrane Intermembrane space Outer membrane 2 H + Enzyme complex Enzyme complex ½ O2 + 2 H + Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 3 ATP

18. Overview of ATP Production NADH releases an electron pair to electron transport system and H + to prime pumps – enough energy to synthesize 3 ATP FADH 2 releases its electron pairs further along electron-transport system – enough energy to synthesize 2 ATP complete aerobic oxidation of glucose to CO 2 and H 2 O produces 36-38 ATP – efficiency rating of 40% - 60% is lost as heat

19. ATP Generated by Oxidation of Glucose Figure 26.7 2 NADH + 2 H + 2 pyruvate Cytosol Mitochondria Glucose 2 NADH + 2 H + 6 NADH + 6 H + Citric acid cycle 2 FADH2 Electron-transport chain H2OO2 Glycolysis Total 36–38 ATP 2 2 4 (net) 28–30 CO2 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ATP

20. 26-20 Glycogen Metabolism ATP is quickly used after it is formed – it is an energy transfer molecule, not an energy storage molecule – converts the extra glucose to other compounds better suited for energy storage (glycogen and fat) glycogenesis - synthesis of glycogen – stimulated by insulin – chains glucose monomers together glycogenolysis – hydrolysis of glycogen – releases glucose between meals – stimulated by glucagon and epinephrine – only liver cells can release glucose back into blood gluconeogenesis - synthesis of glucose from noncarbohydrates, such as glycerol and amino acids – occurs chiefly in the liver and later, kidneys if necessary

21. Glucose Storage and Use Figure 26.8 Extracellular Intracellular Glucose 6-phosphate Glycolysis Key Glycogenesis Glycogenolysis Glycogen synthase Glycogen phosphorylase Pi Glycogen Glucose 6-phosphatase (in liver, kidney, and intestinal cells) Blood glucose Hexokinase (in all cells) Glucose 1-phosphate Pi Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

22. Lipids Triglycerides are stored in body’s adipocytes – constant turnover of lipid molecules every 2 - 3 weeks released into blood, transported and either oxidized or redeposited in other fat cells Lipogenesis - synthesis of fat from other types of molecules – amino acids and sugars used to make fatty acids and glycerol – PGAL can be converted to glycerol

23. Lipids Lipolysis – breaking down fat for fuel – begins with the hydrolysis of a triglyceride to glycerol and fatty acids – stimulated by epinephrine, norepinephrine, glucocorticoids, thyroid hormone, and growth hormone – glycerol easily converted to PGAL and enters the pathway of glycolysis generates only half as much ATP as glucose – beta oxidation in the mitochondrial matrix catabolizes the fatty acid components removes two carbon atoms at a time which bonds to coenzyme A forms acetyl-CoA, the entry point for the citric acid cycle – a fatty acid with 16 carbons can yield 129 molecules of ATP richer source of energy than the glucose molecule

24. Lipogenesis and Lipolysis Pathways Figure 26.9 Glucose PGAL Glucose 6-phosphate Key Lipogenesis Lipolysis Glycerol Fatty acids Glycerol Beta oxidation Acetyl-Co A Stored triglycerides Ketone bodies β -hydroxybutyric acid Acetoacetic acid Acetone Acetyl groups Citric acid cycle Pyruvic acid Fatty acids New triglycerides Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

25. Proteins amino acid pool - dietary amino acids plus 100 g of tissue protein broken down each day into free amino acids may be used to synthesize new proteins – fastest rate of cell division is epithelial cells of intestinal mucosa of all the amino acids absorbed by the small intestine: – 50% comes from the diet – 25% from dead epithelial cells – 25% from enzymes that have digested each other

26. Proteins amino acids in the pool can be converted to others free amino acids also can be converted to glucose and fat or directly used as fuel conversions involve three processes: – deamination – removal of an amino group (-NH 2 ) – amination – addition of -NH 2 – transamination – transfer of -NH 2 from one molecule to another as fuel - first must be deaminated (removal of -NH 2 ) – what remains is keto acid and may be converted to pyruvic acid, acetyl- CoA, or one of the acids of the citric acid cycle – during shortage of amino acids, citric acid cycle intermediates can be aminated and converted to amino acids – in gluconeogenesis, keto acids are used to synthesis glucose

27. Transamination, Ammonia, and Urea when an amino acid is deaminated – its amino group is transferred to a citric acid cycle intermediate, α-ketoglutaric acid, converting it to glutamic acid – glutamic acid can travel from any of the body’s cells to the liver here its -NH 2 is removed converting back α-ketoglutaric acid -NH 2 become ammonia (NH 3 ) which is toxic and cannot accumulate urea cycle – pathway by which the liver combines ammonia with carbon dioxide to produce less toxic waste, urea urea excreted in the urine as one of the body’s nitrogenous wastes

28. Pathways of Amino Acid Metabolism Figure 26.10 Glucose Pyruvic acid Acetyl-CoA NH3 Protein Citric acid cycle Glutamic acid Urea Urine –NH2 CO2  -ketoglutaric acid Amino acids Keto acids Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Urea cycle

29. Liver Functions in Metabolism wide variety of roles in carbohydrate, lipid, and protein metabolism overwhelming majority of its functions are nondigestive hepatocytes perform all functions, except phagocytosis See table 26.6

30. Metabolic States Metabolic rate – Amount of energy liberated in the body per unit time Absorptive state – Nutrients are being absorbed and my be used immediately to meet needs Postabsorptive state – Stomach and small intestines empty, energy needs met from stored fuel