Metabolism and Energy Production: A Comprehensive Overview

1. Lecture Presentation Chapter 12Food as Fuel—A Metabolic Overview Julie Klare Fortis College Smyrna, GA

2. Outline • 12.1 How Metabolism Works • 12.2 Metabolically Relevant Nucleotides • 12.3 Digestion—From Food Molecules to Hydrolysis Products • 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites • 12.5 The Citric Acid Cycle—Central Processing • 12.6 Electron Transport and Oxidative Phosphorylation • 12.7 ATP Production • 12.8 Other Fuel Choices

3. 12.1 How Metabolism Works • Animals get energy from the covalent bonds contained in carbohydrates, fats, and proteins. • In the first stage of metabolism, biomoleculesin food are digested into smaller units through hydrolysis reactions. • Polysaccharides are hydrolyzed into monosaccharide units. • Triglycerides are broken down to glycerol and fatty acids. • Proteins are hydrolyzed into their amino acid units.

4. 12.1 How Metabolism Works The molecules produced by the breakdown are absorbed through the intestinal wall into the bloodstream and transported to different tissues for use by the cells. In the cells, the hydrolysis products are broken down into a few common metabolites containing two or three carbons. Metabolites are chemical intermediates formed by enzyme-catalyzed reactions in the body.

5. 12.1 How Metabolism Works As long as cells have oxygen and are producing energy, two-carbon acetyl groups can be broken down further to carbon dioxide through the citric acid cycle. This cycle works to produce the molecules ATP, nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FADH2).

6. 12.1 How Metabolism Works Chemical reactions that occur in living systems are biochemical reactions. Chemical reactions occur in a series called a metabolic pathway. The sugar molecule glucose (containing six carbons) is broken down to two molecules of pyruvate (three carbons each) through a series of chemical reactions referred to as glycolysis. Metabolism can be considered in two parts, catabolism and anabolism.

7. 12.1 How Metabolism Works Catabolism refers to chemical reactions in which larger molecules are broken down into a few common metabolites. These reactions tend to be exergonic (-G). Anabolism refers to chemical reactions in which metabolites combine to form larger molecules. These reactions tend to be endergonic (+G). The energy released during catabolic reactions is captured in ATP and used to drive anabolic reactions.

8. 12.1 How Metabolism Works

9. 12.1 How Metabolism Works In animals, a cell membrane separates the materials inside the cell from the exterior aqueous environment. The nucleus contains DNA that controls cell replication and protein synthesis for the cell. The cytoplasm consists of all the material between the nucleus and the cell membrane. The cytosol is the fluid part of the cytoplasm. It is the aqueous solution of electrolytes and enzymes that catalyzes many of the cell’s chemical reactions.

10. 12.1 How Metabolism Works Within the cytoplasm are organelles. Ribosomes are the sites of protein synthesis. Mitochondria are the energy-producing factories of the cells. A mitochondrion consists of an outer membrane, an inner membrane, and an intermembrane matrix. Enzymes in the matrix and inner membrane catalyze the oxidation of carbohydrates, fats, and amino acids.

11. 12.1 How Metabolism Works

12. 12.1 How Metabolism Works

13. 12.2 Metabolically Relevant Nucleotides Nucleotides act as energy exchangers and can also be coenzymes. All of these nucleotides have two forms:a high-energy form and a low-energy form. They consist of some basic components:the nucleoside adenosine, a phosphate, and a five-carbon sugar. Many of these molecules also have a vitamin within their structure.

14. 12.2 Metabolically Relevant Nucleotides

15. 12.2 Metabolically Relevant Nucleotides

16. 12.2 Metabolically Relevant Nucleotides

17. 12.2 Metabolically Relevant Nucleotides ATP is often referred to as the energy currency of the cell. ATP can undergo hydrolysis: during hydrolysis, energy is released as a product, so in this case, ATP is the high-energy form and ADP is the low-energy form. The energy given off during the hydrolysis of ATP can be coupled to drive a chemical reaction that requires energy.

18. 12.2 Metabolically Relevant Nucleotides NADH/NAD+ and FADH2/FAD Nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) are energy-transferring compounds with a high-energy form that is reduced (hydrogen added) and a low-energy form that is oxidized (hydrogen removed). The abbreviations for these forms are NADH (reduced form) and NAD+ (oxidized form) and FADH2 (reduced form) and FAD (oxidized form). The active end of each molecule contains a vitamin component. Nicotinamide is derived from the vitamin niacin (B3), and riboflavin (B2) is found in FAD.

19. 12.2 Metabolically Relevant Nucleotides Acetyl Coenzyme A and Coenzyme A Another important energy exchanger is coenzyme A (CoA). The two forms of this compound are acetyl coenzyme A (high energy) and coenzyme A (low energy). Energy is released from acetyl coenzyme A when theC—S bond in the thioester functional group is hydrolyzed, producing an acetyl group and coenzyme A. CoA contains adenosine, three phosphates, anda pantothenic acid (vitamin B5)-derived portion.

20. 12.3 Digestion—From Food Molecules to Hydrolysis Products Carbohydrates Starch (amylose and amylopectin) begins to be digested in your mouth by alpha-amylase in saliva. This salivary amylase hydrolyzes some of the α-glycosidic bonds in the starch molecules, producing glucose, the disaccharide maltose, and oligosaccharides. Only monosaccharides are small enough to be transported into the bloodstream. To complete the digestion of starch, enzymes in the small intestine hydrolyze starch and disaccharides into monosaccharides. Cellulose cannot be digested because we lack the enzyme cellulase that hydrolyzes its β-glycosidic bonds.

21. 12.3 Digestion—From Food Molecules to Hydrolysis Products

22. Fats Dietary fats are nonpolar molecules, so to assist in digestion, bileis excreted from the gall bladder into the stomach during digestion. Bile contains bile salts, which are amphipathic: they place their nonpolar face toward the dietary fats and their polar face toward the water, forming micelles. Breaking up larger nonpolar globules into smaller droplets (micelles) is called emulsification. The micelles move the dietary fats closer to the intestinal cell wall so cholesterol can be absorbed and triglycerides hydrolyzed. Once across the intestinal wall, free fatty acids and monoglycerides are reassembled as triglycerides while the cholesterol is linked to another free fatty acid forming a cholesterol ester. These are repackaged as a lipoprotein called a chylomicron. Chylomicrons transport triglycerides to the tissues, where they are used for energy production or stored. 12.3 Digestion—From Food Molecules to Hydrolysis Products

23. 12.3 Digestion—From Food Molecules to Hydrolysis Products

24. Proteins Protein digestion begins in the stomach, where proteins are denatured (unfolded) by the acidic digestive juices. Digestive enzymes like pepsin, trypsin, and chymotrypsin hydrolyze peptide bonds. Amino acids are absorbed into the bloodstream for delivery to the tissues. 12.3 Digestion—From Food Molecules to Hydrolysis Products

25. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites The Chemical Reactions in Glycolysis In the body, energy must be transferred in small amounts to minimize the heat released in the process. Reactions that produce energy are coupled with reactions that require energy, thereby helping to maintain a constant body temperature. In glycolysis, energy is transferred through phosphate groups undergoing condensation and hydrolysis reactions. There are 10 chemical reactions in glycolysis that result in the formation of two molecules of pyruvate from one molecule of glucose.

26. The Chemical Reactions in Glycolysis The first five reactions require an energy investment of two molecules of ATP, which are used to add two phosphate groups to the sugar molecule. This molecule is split into two sugar phosphates. Reactions 6 through 10 generate two high-energy NADH molecules during the addition of two more phosphates and four ATP molecules when the four phosphates are removed from the sugar phosphates. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

27. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

28. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

29. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

30. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

31. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

32. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

33. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

34. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

35. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

36. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

37. Regulation of Glycolysis The main step of regulation in glycolysis is step 3. The enzyme phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, is heavily regulated by the cells. ATP acts as an inhibitor of phosphofructokinase. If cells have plenty of ATP, glycolysis slows down. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

38. The Fates of Pyruvate Aerobic conditions: pyruvate produces more energy for the cell when the carboxylate functional group of pyruvate is liberated as CO2 during oxidative decarboxylation. The acetyl group binds to coenzyme A during the oxidation through a sulfur atom, creating a thioester functional group and acetyl CoA. This reaction occurs in the mitochondria. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

39. The Fates of Pyruvate Anaerobic conditions: the middle carbonyl in pyruvate is reduced (hydrogen added) to an alcohol group, and lactate is formed. The hydrogen (and energy) required for this reaction is supplied by NADH and H+, producing NAD+. The NAD+ produced funnels back into glycolysis to oxidize more glyceraldehyde-3-phosphate (step 6), providing a small amount of ATP. This reaction occurs in the cytosol. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

40. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

41. Yeast converts pyruvate to ethanol under anaerobic conditions. This process is called fermentation. In the preparation of alcoholic beverages, yeast produces pyruvate from glucose in grape juices and under low-oxygen conditions transforms pyruvate into ethanol. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites

42. 12.4 Glycolysis—From Hydrolysis Products to Common Metabolites Fructose and Glycolysis Fructose is readily taken up in the muscle and liver. In the muscles, it is converted to fructose-6-phosphate, entering glycolysis at step 3. In the liver, it is converted to the trioses used in step 5. Fructose that enters a cell flows from reaction 5 to 10. Fructose uptake by the cells is not regulated by insulin: all fructose in the bloodstream is forced into catabolism. Glycolysis is regulated at step 3. The triose products created in the liver provide an excess of reactants that create excess pyruvate and acetyl CoA that, if not required for energy by the cells, is converted to fat.

43. 12.5 The Citric Acid Cycle—Central Processing During aerobic catabolism, glucose, amino acids, and fatty acids funnel into and out of the citric acid cycle. The citric acid cycle degrades two-carbon acetyl groups from acetyl CoA into CO2 and generates the high-energy molecules NADH and FADH2. The initial reaction is a condensation reaction between acetyl CoA and the four-carbon molecule oxaloacetate. The six-carbon citrate loses first one and then a second carbon as CO2, forming the four-carbon succinyl CoA. These carbon–carbon bond-breaking reactions transfer energy and produce NADH from the coenzyme NAD+. Succinyl CoA then runs through a set of reactions regenerating oxaloacetate, and the cycle begins again.

44. 12.5 The Citric Acid Cycle—Central Processing Reactions of the Citric Acid Cycle Reaction 1, Formation of Citrate: The acetyl group from acetyl CoA (two carbons) combines with oxaloacetate (four carbons), forming citrate (six carbons) and CoA. Reaction 2, Isomerization to Isocitrate:The –OH and one of the –H atoms are swapped in citrate to form isocitrate. This rearrangement is necessary because isocitrate is oxidized in the next reaction. Reaction 3, First Oxidative Decarboxylation (Release of CO2): An alcohol undergoes oxidation (two hydrogens removed) to a ketone called -ketoglutarate, and NAD+is reduced to NADH, accepting the proton and electrons removed during the oxidation. The six-carbon isocitrateis decarboxylated to the five-carbon -ketoglutarate.

45. 12.5 The Citric Acid Cycle—Central Processing Reactions of the Citric Acid Cycle Reaction 4, Second Oxidative Decarboxylation: The thiol group of CoA is oxidized (loses a hydrogen), and another NAD+ is reduced to NADH. Alpha-ketoglutarate (five carbons) is decarboxylated into a succinyl group (four carbons). The CoA is bonded to the succinyl group, thus producing succinyl CoA. Reaction 5, Hydrolysis of Succinyl CoA: Succinyl CoA undergoes hydrolysis to succinate and coenzyme A. The energy produced produces the high-energy nucleotide guanosine triphosphate or GTP from GDP and Pi. GTP is converted to ATP in the cell.

46. 12.5 The Citric Acid Cycle—Central Processing Reactions of the Citric Acid Cycle Reaction 6, Dehydrogenation of Succinate: One hydrogen is eliminated from each of the two central carbons of succinate, forming a trans C=C bond, thus producing fumarate. These two hydrogens reduce the coenzyme FAD to FADH2. Reaction 7, Hydration of Fumarate: Water adds to the trans double bond of fumarate as –H and –OH forming malate. Reaction 8, Oxidation of Malate: As in reaction 3, the secondary alcohol of malate is oxidized to a ketone forming oxaloacetate, providing protons and electrons to reduce the coenzyme NAD+ to NADH.

47. 12.5 The Citric Acid Cycle—Central Processing One turn of the citric acid cycle produces a net energy output of three NADH, one FADH2, and one GTP (which forms ATP). Two CO2 and one CoA also are produced. The net reaction for one turn of this eight-step cycle is

48. 12.5 The Citric Acid Cycle—Central Processing

49. 12.6 Electron Transport and Oxidative Phosphorylation Two ATP are produced in glycolysis and two ATP in the citric acid cycle. Where is all the energy? NADH and FADH2 are produced in glycolysis (two NADH per glucose), from pyruvate oxidation to acetyl CoA(two NADH per glucose), and in the citric acid cycle(six NADH and two FADH2 per glucose). High-energy reduced forms of the nucleotides transfer electrons and hydrogens through the inner mitochondrial membrane and to form H2O. The energy generated as a result of this process is used to drive the reaction of ADP to form ATP. This is called oxidative phosphorylation.

50. Mitochondria are the ATP factories of the cell. Reduced nucleotides from the citric acid cycle are produced here, and their energy upon oxidation is used to generate ATP. The reactions of the citric acid cycle occur in the matrix of the mitochondria. The reduced nucleotides, NADH and FADH2, begin their journey through the inner membrane here. Enzyme complexes I through V are embedded in the inner membrane of the mitochondria and electron carriers that transport the electrons and protons of NADH and FADH2 through the inner mitochondrial membrane. Two of the electron carriers, coenzyme Q and cytochrome c, are not firmly attached to any one complex and shuttle electrons between the complexes. 12.6 Electron Transport and Oxidative Phosphorylation