Chapter 23 Metabolism and Energy production

1. Chemistry 203 Chapter 23 Metabolism and Energy production

2. Metabolism Chemical reactions in cells that break down or build molecules. It produces energy and provide substances to cell growth. The sum of all the chemical reactions that take place in an organism. Catabolic reactions: Complex molecules  Simple molecules + Energy Anabolic reactions: Simple molecules + Energy (in cell) Complex molecules

3. Metabolic Pathway A series of consecutive reactions. A linear pathway is the series of reactions that generates a final product different from any of the reactants. A cyclic pathway is the series of reactions that regenerates the first reactant.

4. Metabolism in cell Mitochondria Urea NH4+ Proteins Amino acids e Citric Acid cycle Glucose Fructose Galactose Carbohydrates Polysaccharides e Glucose Pyruvate Acetyl CoA CO2 & H2O Glycerol Lipids Fatty acids Stage 3: Oxidation to CO2, H2O and energy Stage 2: Degradation and some oxidation Stage 1: Digestion and hydrolysis (Formation of Acetyl CoA)

5. Cell Structure Nucleus Membrane Mitochondria Cytoplasm (Cytosol)

6. Cell Structure Nucleus: consists the genes that control DNA replication and protein synthesis of the cell. Cytoplasm: consists all the materials between nucleus and cell membrane. Cytosol: fluid part of the cytoplasm (electrolytes and enzymes). Organelles:the specialized structures within cells (carry out specific functions). Mitochondria: energy producing factories. Enzymes in matrix catalyze the oxidation of carbohydrates, fats , and amino acids. Produce CO2, H2O, and energy.

7. ATP and Energy • Adenosine triphosphate (ATP) is produced from the oxidation of food. • Has a high energy. • Can be hydrolyzed and produce energy.

8. Pi (adenosine triphosphate) (adenosine diphosphate) (inorganic phosphate) ATP and Energy - We use this energy for muscle contraction, synthesis an enzyme, send nerve signal, and transport of substances across the cell membrane. - 1-2 million ATP molecules may be hydrolysis in one second (1 gram in our cells). - When we eat food, catabolic reactions provide energy to recreate ATP. ADP + Pi + 7.3 kcal/mol  ATP Phosphorylation is the reverse reaction, where a phosphate group is added to ADP.

9. Coupled Reactions Coupled reactions are pairs of reactions that occur together. The energy released by one reaction is absorbed by the other reaction. ATP + H2O ADP + HPO42− ∆H = −7.3 kcal/mol energy is released Exothermic: a favorable reaction ADP + HPO42- ATP + H2O ∆H = +7.3 kcal/mol energy is absorbed Endothermic: an unfavorable reaction

10. Coupled Reactions The hydrolysis of ATP provides the energy for the phosphorylation of glucose. Coupling an energetically unfavorable reaction with a favorable one that releases more energy than the amount required is common in biological reactions.

11. Stage 1: Digestion Convert large molecules to smaller ones that can be absorbed by the body. Carbohydrates Lipids (fat) Proteins

12. Digestion: Carbohydrates Salivary amylase Dextrins + Mouth Polysaccharides + Maltose Glucose Stomach pH = 2 (acidic) Small intestine pH = 8 Dextrins α-amylase(pancreas) Glucose Glucose Maltase + Maltose Galactose Glucose Lactase + Lactose Fructose Glucose Sucrase + Sucrose Bloodstream Liver (convert all to glucose)

13. Digestion: Lipids (fat) Fatty acid H2C OH H2C lipase (pancreas) HC Fatty acid + 2H2O HC Fatty acid + 2 Fatty acids Small intestine H2C Fatty acid H2C OH Triacylglycerol Monoacylglycerol Intestinal wall Monoacylglycerols + 2 Fatty acids → Triacylglycerols Protein Lipoproteins Chylomicrons Lymphatic system Bloodstream Enzymes hydrolyzes Glycerol + 3 Fatty acids Cells liver Glucose

14. Digestion: Proteins HCl Pepsinogen Pepsin Stomach Proteins Polypeptides denaturation + hydrolysis Small intestine Typsin Chymotrypsin Polypeptides Amino acids hydrolysis Intestinal wall Bloodstream Cells

15. Some important coenzymes oxidation Coenzyme + Substrate Coenzyme(+2H) + Substrate(-2H) Reduced Oxidized 2 H atoms 2H+ + 2e- NAD+ Coenzymes FAD Coenzyme A

16. ADP NAD+ Nicotinamide adenine dinucleotide (vitamin) (Vitamin B3) fish, nuts Ribose

17. + NAD+ • Is an oxidizing agent. • Participates in reactions that produce (C=O) such as oxidation of alcohols to aldehydes and ketones. O CH3-CH2-OH + NAD+ CH3-C-H + NADH + H+ NAD+ + 2H+ + 2e- NADH + H+ Reduced

18. FAD Flavin adenine dinucleotide (Vitamin B2) (sugar alcohol) Soybeans, almonds, liver ADP

19. H H R-C-C-R + FAD R-C=C-H + FADH2 H H H H FAD • Is an oxidizing agent. • Participates in reaction that produce (C=C) such as dehydrogenation of alkanes. Reduced

20. Coenzyme A (CoA) Coenzyme A Aminoethanethiol ( vitamin B5) whole grain, egg

21. Coenzyme A (CoA) O O - It activates acyl groups (RC-), particularly the Acetyl group (CH3C-). O O CH3-C- + HS-CoA CH3-C-S-CoA Acetyl group Coenzyme A Acetyl CoA O R-C-S-R’ A Thioester When the thioester bond is broken, 7.5 kcal/mol of energy is released.

22. Metabolism in cell Mitochondria Urea NH4+ Proteins Amino acids e Citric Acid cycle Glucose Fructose Galactose Carbohydrates Polysaccharides e Glucose Pyruvate Acetyl CoA CO2 & H2O Glycerol Lipids Fatty acids Stage 3: Oxidation to CO2, H2O and energy Stage 2: Degradation and some oxidation Stage 1: Digestion and hydrolysis (Formation of Acetyl CoA)

23. Stage 2: Formation of Acetyl CoA Glycolysis: Oxidation of glucose • We obtain most of our energy from glucose. • Glucose is produced when we digest the carbohydrates in our food. • We do not need oxygen in glycolysis (anaerobic process). 2 ATP 2 ADP + 2Pi O C6H12O6 + 2 NAD+ 2CH3-C-COO- + 2 NADH + 4H+ Glucose Pyruvate Inside of cell (Cytoplasm)

24. Pathways for pyruvate - Pyruvate can produce more energy. Aerobic conditions: if we have enough oxygen. Anaerobic conditions: if we do not have enough oxygen.

25. Aerobic conditions • Pyruvate is oxidized and a C atom remove (CO2). • Acetyl is attached to coenzyme A (CoA). • Coenzyme NAD+ is required for oxidation. O O O CH3-C-C-O- + HS-CoA + NAD+ CH3-C-S-CoA + CO2 + NADH pyruvate Coenzyme A Acetyl CoA Important intermediate product in metabolism.

26. NAD+ O O NADH + H+ HO O CH3-C-C-O- CH3-C-C-O- H pyruvate Lactate Reduced Anaerobic conditions • When we exercise, the O2 stored in our muscle cells is used. • Pyruvate is reduced to lactate. • Accumulation of lactate causes the muscles to tire and sore. • Then we breathe rapidly to repay the O2. • Most lactate is transported to liver to convert back into pyruvate.

27. Glycogen • If we get excess glucose (from our diet), glucose convert to glycogen. • It is stored in muscle and liver. • We can use it later to convert into glucose and then energy. • When glycogen stores are full, glucose is converted to triacylglycerols and stored as body fat.

28. Metabolism in cell Mitochondria Urea NH4+ Proteins Amino acids e Citric Acid cycle Glucose Fructose Galactose Carbohydrates Polysaccharides e Glucose Pyruvate Acetyl CoA CO2 & H2O Glycerol Lipids Fatty acids Stage 3: Oxidation to CO2, H2O and energy Stage 2: Degradation and some oxidation Stage 1: Digestion and hydrolysis (Formation of Acetyl CoA)

29. Stage 3: Citric Acid Cycle (Kerbs Cycle) • Is a central pathway in metabolism. • Uses acetyl CoA from the degradation of carbohydrates, lipids, and proteins. • Two CO2 are given off. • There are four oxidation steps in the cycle provide H+ and electrons to reduce FAD and NAD+ (FADH2 and NADH). 8 reactions

30. Reaction 1 Formation of Citrate O CH3-C-S-CoA Acetyl CoA + COO- CH2 COO- H2O HO COO- + CoA-SH C C=O Citrate Synthase Oxaloacetate CH2 CH2 COO- COO- Coenzyme A Citrate

31. Reaction 2 Isomerisation to Isocitrate • Because the tertiary –OH cannot be oxidized. (convert to secondary –OH) COO- COO- CH2 CH2 Isomerization HO H COO- COO- C C Aconitase H HO CH2 C COO- COO- Isocitrate Citrate

32. Reaction 3 First oxidative decarboxylation (CO2) • Oxidation (-OH converts to C=O). • NAD+ is reduced to NADH. • A carboxylate group (-COO-) is removed (CO2). COO- COO- COO- CH2 CH2 CH2 H H COO- COO- C C CH2 H+ + CO2 Isocitrate dehydrogenase H HO O O C C C COO- COO- COO- Isocitrate α-Ketoglutrate

33. Reaction 4 Second oxidative decarboxylation (CO2) • Coenzyme A convert to succinyl CoA. • NAD+ is reduced to NADH. • A second carboxylate group (-COO-) is removed (CO2). COO- COO- CH2 CH2 CH2 CH2 + CO2 O O C C α-Ketoglutrate dehydrogenase COO- S-CoA Succinyl CoA α-Ketoglutrate (a Thioester)

34. Reaction 5 Hydrolysis of Succinyl CoA • Energy from hydrolysis of succinyl CoA is used to add a phosphate group (Pi) to GDP (guanosine diphosphate). • The hydrolysis of GTP is used to add a Pi to ADP to produce ATP. GTP + ADP → GDP+ ATP COO- COO- CH2 CH2 + H2O + GDP + Pi + GTP + CoA-SH CH2 CH2 O C COO- S-CoA Succinate Succinyl CoA

35. Reaction 6 Dehydrogenation of Succinate • H is removed from two carbon atoms. • Double bond is produced. • FAD is reduced to FADH2. COO- COO- CH2 CH CH2 CH Succinate dehydrogenase COO- COO- Fumarate Succinate

36. Reaction 7 Hydration • Water adds to double bond of fumarate to produce malate. COO- COO- H2O CH H HO C CH CH2 COO- COO- Fumarate Malate

37. Reaction 8 Dehydrogenation forms oxaloacetate • -OH group in malate is oxidized to oxaloacetate. • Coenzyme NAD+ is reduced to NADH + H+. COO- COO- + H+ H HO C C=O CH2 CH2 COO- COO- Oxaloacetate Malate The product of step [8] is the starting material for step [1].

38. Summary The catabolism of proteins, carbohydrates, and fatty acids all feed into the citric acid cycle at one or more points: Citric Acid Cycle

39. Summary

40. Summary

41. Summary The main function of the citric acid cycle is to produce reduced coenzymes (NADH and FADH2). These molecules enter the electron transport chain (Stage 4) and ultimately produce ATP. Feedback Mechanism The rate of the citric acid cycle depends on the body’s need for energy. When energy demands are high and ATP is low → the cycle is activated. When energy demands are low and NADH is high → the cycle is inhibited.

42. Stage 4: Electron Transport & Oxidative Phosphorylation • Most of energy generated during this stage. • It is an aerobic respiration (O2 is required). 1. Electron Transport Chain (Respiratory Chain) 2. Oxidative Phosphorylation

43. Stage 4: Electron Transport Chain H+ and electrons from NADH and FADH2 are carried by an electron carrier until they combine with oxygen to form H2O. FMN (Flavin Mononucleotide) Fe-S clusters Electron carriers Coenzyme Q (CoQ) Cytochrome (cyt)

44. (Vitamin B2) (sugar alcohol) - FMN (Flavin Mononucleotide) H 2H+ + 2e- H - FMN + 2H+ + 2e-→ FMNH2 Reduced

45. Fe-S Clusters S S Cys S Cys Cys S Cys + 1 e- Fe3+ Fe2+ S S S S Cys Cys Cys Cys Fe3+ + 1e-Fe2+ Reduced

46. Coenzyme Q (CoQ) OH 2H+ + 2e- OH Reduced Coenzyme Q (QH2) Coenzyme Q Q + 2H+ + 2e-→ QH2 Reduced

47. Cytochromes (cyt) • They contain an iron ion (Fe3+) in a heme group. • They accept an electron and reduce to (Fe2+). • They pass the electron to the next cytochrome and they are oxidized back to Fe3+. Fe3+ + 1e- Fe2+ Oxidized Reduced cyt b, cyt c1, cyt c, cyt a, cyt a3

48. Electron Transport Chain Mitochondria 4 enzyme complexes (I, II, III and IV)

49. Electron Transport Chain Complex I Oxidized NADH + H+ + FMN → NAD+ + FMNH2 FMNH2+ Q → QH2 + FMN NADH + H+ + Q → QH2 + NAD+ Complex II FADH2 + Q → FAD + QH2 Oxidized

50. Electron Transport Chain Complex III QH2 + 2 cyt b (Fe3+) → Q + 2 cyt b (Fe2+) + 2H+ Complex IV Aerobic 4H+ + 4e- + O2→ 2H2O From reduced coenzymes or the matrix From inhaled air From the electron transport chain