Chapter 19 & 20 Metabolic pathway & Energy production

1. Chemistry 20 Chapter 19 & 20 Metabolic pathway & Energy production

2. Metabolism Chemical reactions in cells that break down or build molecules. It produces energy and provide substances to cell growth. Catabolic reactions: Complex molecules  Simple molecules + Energy Anabolic reactions: Simple molecules + Energy (in cell) Complex molecules

3. 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 Step 3: Oxidation to CO2, H2O and energy Step 1: Digestion and hydrolysis Step 2: Degradation and some oxidation

4. Cell Structure Nucleus Membrane Mitochondria Cytoplasm (Cytosol)

5. 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). Mitochondria: energy producing factories. Enzymes in matrix catalyze the oxidation of carbohydrates, fats , and amino acids. Produce CO2, H2O, and energy.

6. 3 Phosphates Ribose ATP and Energy • Adenosine triphosphate (ATP) is produced from the oxidation of food. • Has a high energy. • Can be hydrolyzed and produce energy.

7. 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

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

9. 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)

10. 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

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

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

13. ADP NAD+ Nicotinamide adenine dinucleotide (vitamin) Ribose

14. + NAD+ • Is a 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+

15. FAD Flavin adenine dinucleotide (Vitamin B2) (sugar alcohol) ADP

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

17. Coenzyme A (CoA) HS-CoA Coenzyme A Aminoethanethiol ( vitamin B5)

18. Coenzyme A (CoA) - It activates acyl groups, particularly the acetyl group. O O CH3-C- + HS-CoA CH3-C-S-CoA Acetyl group Coenzyme A Acetyl CoA

19. 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 Step 3: Oxidation to CO2, H2O and energy Step 1: Digestion and hydrolysis Step 2: Degradation and some oxidation

20. Step 2: Glycolysis • 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

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

22. 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.

23. 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.

24. 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.

25. 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 Step 3: Oxidation to CO2, H2O and energy Step 1: Digestion and hydrolysis Step 2: Degradation and some oxidation

26. Step 3: Citric Acid 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

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

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

29. 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 CO2 H HO O O C C C COO- COO- COO- Isocitrate α-Ketoglutrate

30. 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 COO- S-CoA α-Ketoglutrate Succinyl CoA

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

32. 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 COO- COO- Fumarate Succinate

33. 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

34. 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

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

36. Summary 12 ATP produced from each acetyl-CoA

37. Electron Transport 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)

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

39. 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

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

41. 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

42. Electron Transfer Mitochondria

43. Electron Transfer Complex I NADH + H+ + FMN → NAD+ + FMNH2 FMNH2+ Q → QH2 + FMN NADH + H+ + Q → QH2 + NAD+ Complex II FADH2 + Q → FAD + QH2

44. Electron Transfer Complex III QH2 + 2 cyt b (Fe3+) → Q + 2 cyt b (Fe2+) + 2H+ Complex IV 4H+ + 4e- + O2→ 2H2O

45. Oxidative Phosphorylation Transport of electrons produce energy to convert ADP to ATP. ADP + Pi + energy → ATP

46. Chemiosmotic model • H+ make inner mitochondria acidic. • Produces different proton gradient. • H+ pass through ATP synthase (a protein complex). ATP synthase

47. Total ATP Glycolysis: 6 ATP Pyruvate: 6 ATP Citric acid cycle: 24 ATP Oxidation of glucose 36 ATP C6H12O6 + 6O2 + 36 ADP + 36 Pi→ 6CO2 + 6H2O + 36 ATP

48. 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 Step 3: Oxidation to CO2, H2O and energy Step 1: Digestion and hydrolysis Step 2: Degradation and some oxidation

49.  α  oxidation O CH3-(CH2)14-CH2-CH2-C-OH Oxidation of fatty acids • Oxidation happens in step 2 and 3. • Each beta oxidation produces acetyl CoA and a shorter fatty acid. • Oxidation continues until fatty acid is completely break down to acytel CoA.

50. Oxidation of fatty acids Fatty acid activation - Before oxidation, they activate in cytosol. O O + ATP + HS-CoA R-CH2-C-S-CoA R-CH2-C-OH + H2O + AMP + 2Pi Fatty acid Fatty acyl CoA -Oxidation: 4 reactions