BIO 169 METABOLISM AND ENERGETICS CHAPTER 25

1. BIO 169 METABOLISM AND ENERGETICS CHAPTER 25 created by Dr. C. Morgan

2. TOPICS Introduction and Overview Carbohydrate Metabolism Lipid Metabolism Protein Metabolism Nucleic Acid Metabolism Metabolic Interactions Diet and Nutrition Bioenergetics

3. Introduction and Overview Objectives Discuss the relationship between nutrients, the digestive system, the cardiovascular system, and cellular metabolism. Review the storage of excess nutrients. Review the definition of metabolism. Discuss the metabolic functions within cells. Discuss the roles of catabolism and anabolism.

4. Introduction Metabolism is the sum of all chemical reactions taking place in the body. Chemical reactions occur within the cytosol and organelles of cells and in the extracellular fluids. Our interest is in the ability of a cell to extract from nutrients sufficient chemical bond energy to produce ATP, the energy currency for cellular work. Additional high energy compounds are produced but will not be discussed in any detail. Oxygen, required for efficient nutrient use, is supplied to the blood by the lungs. The digestive system makes the nutrients available to cells via the cardiovascular delivery system.

5. Introduction (cont) Ideally, nutrient intake matches the metabolic demand of cells. If you take in more food than you need, it is stored in adipose tissue for subsequent use. Hormones, with some help from the nervous system, guide cellular metabolic activities, the storage of reserves, and the release of reserves from storage when they are needed. Nutrition is the absorption of nutrients from food. The fate of the absorbed nutrients will be the focus of our discussions.

6. Introduction (cont) Metabolic activities occurring within cells is cellular metabolism which performs several functions: * recycles cellular components (metabolic turnover) * provides energy for cell division and growth *carries out specialized activities of differentiated cells including secretion, contraction, nervous system communication via action potentials Catabolism is the breakdown of nutrients to harness energy in the chemical bonds of new molecules, especially high energy compounds such as ATP. For efficiency, catabolism occurs in many small steps which allows more released energy to be captured.

7. Introduction (cont) ATP produced from catabolic reactions links catabolism to anabolism, the building of new organic molecules needed by the cell to carry out its activities. New organic molecules are used for * ongoing maintenance and repair * growth * production of cellular secretions * building and storage of energy reserves. Catabolism and anabolism depend on the availability of a nutrient pool provided from digestion, absorption, and distribution.

8. Introduction (cont) Fig. 1

9. Introduction (cont) Relationships--Metabolic turnover and ATP production Fig. 2

10. Introduction (cont) Overview of nutrient use in cellular metabolism Fig. 3

11. TOPICS Introduction and Overview Carbohydrate Metabolism Lipid Metabolism Protein Metabolism Nucleic Acid Metabolism Metabolic Interactions Diet and Nutrition Bioenergetics

12. Carbohydrate Metabolism Objectives Show the formula for glucose catabolism. Discuss glycolysis. Describe the production of ATP in mitochondria. Show the energy yield of glycolysis and aerobic cellular respiration. Describe alternative catabolic pathways when there is insufficient glucose available.

13. Carbohydrate Metabolism From the nutrient pool cells first use the available carbohydrates, then the lipids, and amino acids third. Carbohydrate metabolism is mainly the story of glucose catabolism – C6H12O6 + 6O2 6 CO2 + 6 H2O There are two steps to the catabolism of glucose, glycolysis which occurs in the cytosol and aerobic respiration which occurs in the mitochondria. The useful products of glycolysis are 2 pyruvic acid molecules, 2 NADH, and 2 ATP for cellular use. The pyruvic acids and NADHs move into the mitochondrion for further processing which yields much more ATP.

14. Carbohydrate Metabolism (cont) CYTOSOL Fig. 4

15. Carbohydrate Metabolism (cont) Needed for glycolysis are *glucose molecules *specific catalytic enzymes for each reaction *ATP, ADP, and inorganic phosphate (Pi) *NAD+ coenzyme carrier molecules that remove hydrogen atoms during one of the reaction steps The use of 2 ATPs prepares glucose for catabolism. NAD+ becomes reduced and takes on a hydrogen atom and one additional electron to become NADH. NADH moves into the mitochondrion where it will donate its electrons to the electron transport chain and H+ to solution.

16. Carbohydrate Metabolism (cont) Reduction of NAD+ H+ proton H+  oxidation of organic molecule More than one hydrogen atom may be removed at a time. NAD+ takes on 2 electrons, one proton, and leaves the other proton in solution  NADH + H+ FADH takes on one complete hydrogen (in mitochondria)

17. Carbohydrate Metabolism (cont) Phosphorylation of ADP occurs by two methods. *Substrate-level phosphorylation is the transfer of a high energy phosphate from a substrate molecule directly to ADP. ATP is made by substrate-level phosphorylation during glycolysis in the cytosol and in the TCA cycle which takes place in the mitochondrial matrix *Oxidative phosphorylation makes ATP using the electron transport chain, oxygen, and chemiosmosis (a special process occurring in the mitochondrion>90% of the ATP). Review: oxidation is the loss of electrons from a molecule; reduction is the gain of electrons by a molecule. During coupled oxidation–reduction reactions, hydrogens are also transferred to the carrier molecules.

18. Carbohydrate Metabolism (cont) Recall that it is electrons that participate in chemical reactions. Two types of carrier molecules, NADH and FADH2, that deliver hydrogen atoms and their electrons to the electron transport chain of the mitochondrion are important because * for each NADH delivered, 3 ATPs are generated and * for each FADH2 delivered, 2 ATPs are generated. The CO2 that is given off as waste originates from the carbons and oxygen in glucose. The only thing actually harvested from glucose is the energy from its chemical bonds and some hydrogens that are temporarily used to create an electrochemical gradient in the mitochondrion.

19. Carbohydrate Metabolism (cont) The mitochondrion is a double membrane organelle with an inner compartment containing a fluid called the matrix and an outer intermembrane space which also contains fluid. The outer membrane has large pores that allow ions, small molecules, and carriers to cross. A carrier protein contained in the inner membrane moves pyruvic acid molecules into the matrix. Each pyruvic acid is converted to an acetyl- Co-A (2 carbons) and in the process produces an NADH and a CO2 as waste.

20. Carbohydrate Metabolism (cont) TCA cycle completes the catabolism of glucose. (via GTP) 2 turns / glucose 20 Fig. 5

21. Carbohydrate Metabolism (cont) NADH and FADH2 donate hydrogens and electrons. The mitochondrial electron transport system (ETS) is a series of complex molecules that undergo coupled oxidation-reduction reactions. final electron acceptor Energy is used to move H+s into the intermembrane space. Fig. 6 a

22. Carbohydrate Metabolism (cont) Aerobic respiration generates most of the ATP Fig. 6 b

23. Carbohydrate Metabolism (cont) The donated electrons pass from one molecule to another with the hydrogen protons pumped to the outer compartment of the mitochondrion, creating an electrochemical gradient. As H+s pass back to the inner compartment through a special membrane protein, ATPs are made. Every 2 H+s passing back into the matrix provides enough energy to produce one ATP by the special protein. Oxygen is the last electron acceptor where it also combines with the H+ to form metabolic water. This is where you consume oxygen. With insufficient oxygen, electron transport stops. Total = 36 ATP from each glucose using glycolysis + ETS.

24. Carbohydrate Metabolism (cont) 

25. Carbohydrate Metabolism (cont) Glycogen, triglycerides, and proteins are storage forms of energy. When there is insufficient glucose, triglyceride fragments and amino acids are able to enter glycolysis or the TCA cycle at various points to be catabolized. Skeletal muscle and the liver store glycogen.

26. Carbohydrate Metabolism (cont) Overview Glucose may be synthesized from other starting materials in a process called gluconeogenesis.

27. Carbohydrate Metabolism (cont) Glycogenesis stores excess glucose as glycogen in the liver and skeletal muscle. Glycogenolysis breaks down glycogen stores to yield glucose for metabolism. Note interconversions to intermediates of glycolysis. 27 Fig. 8

28. TOPICS Introduction and Overview Carbohydrate Metabolism Lipid Metabolism Protein Metabolism Nucleic Acid Metabolism Metabolic Interactions Diet and Nutrition Bioenergetics

29. Lipid Metabolism Objectives Discuss the mechanisms for lipid catabolism. Describe the importance of lipids as energy reserves. Discuss the synthesis of lipids. Describe the transport and distribution of lipids. Discuss the relationships of dietary fats and cholesterol in health.

30. Lipid Metabolism Lipolysis is catabolism of lipids and beta-oxidation is the catabolism of fatty acids. More energy is gained from the catabolism of a gram of lipids than either carbohydrates or proteins. Triglycerides represent most of the lipids stored in the body. A triglyceride is catabolized into its component parts— a glycerol molecule and three fatty acid chains. The glycerol molecule enters the TCA cycle after it is converted to pyruvic acid by enzymes in the cytosol.

31. Lipid Metabolism (cont) Beta-oxidation is the catabolism of fatty acid chains. 2 C fragments are removed and converted to acetyl- CoA molecules which then enter the TCA cycle. ATP must be used in the conversion but reduced carriers are formed. Beta oxidation 31 Fig. 9 31

32. Lipid Metabolism (cont) Lipids are the “best” energy stores because they provide large amounts of ATP, are stored in compact droplets contained in the cytosol, and are not degraded by water soluble enzymes. Oxygen is required since lipid catabolism occurs within the mitochondrion by aerobic metabolism. Because their catabolism requires more time, lipid reserves are catabolized during times of rest (muscles) to save valuable glycogen and glucose. Skeletal muscles cycle between carbohydrate and lipid metabolism depending on immediate demand.

33. Lipid Metabolism (cont) Lipid synthesis (lipogenesis) involves the synthesis of glycerol from intermediates of glycolysis and the synthesis of fatty acid chains from acetyl-Co A fragments. Not all fatty acids are able to be synthesized by cells. Linoleic acid and linolenic acid molecules cannot be synthesized so must be obtained from the diet. Such a dietary requirement is an essential fatty acid. These fatty acids which come from plant sources are incorporated into cell membranes and are used to make prostaglandins.

34. Lipid Metabolism (cont) Lipid Synthesis – lipogenesis Lipids may be synthesized from most nutrient fragments. 34 Fig. 10

35. Lipid Metabolism (cont) All cells need lipids for their cell and organelle phospholipid membranes and lipids are needed by some cells to build steroid hormones. Free fatty acids are able to diffuse into cells. Because they are insoluble, lipids circulate as lipoproteins which consist of large glycerides + cholesterol coated with phospholipids and proteins. The lipoprotein complexes, mostly made in the liver, are water soluble and transported in the plasma. The proteins on the outer surface are recognized by cell receptors which determines cellular absorption of particular lipids contained within lipoprotein complexes.

36. Lipid Metabolism (cont) Lipoproteins are grouped according to their size and relative amount of lipid compared to protein. Chylomicronsare the largest (0.03 – 0.05 m) with 95% of their weight triglycerides. Recall these are made by villi cells of the small intestine. Very low-density lipoproteins (VLDLs) (0.025 – 0.075 m) contain a large proportion of triglycerides and some phospholipids + cholesterol that are delivered to peripheral tissues. Intermediate-density lipoproteins (IDLs) contain less triglycerides and more phospholipids + cholesterol in proportion to protein.

37. Lipid Metabolism (cont) High-density lipoproteins (HDLs) (10 nm) contain about equal proportions of lipid and protein with the lipids mostly cholesterol and phospholipids (not triglycerides). HDLs are moving materials from peripheral tissues back to the liver for storage or excretion in the bile. These lipids do not accumulate in vessels so sometimes they are called the “good cholesterol”.

38. Lipid Metabolism (cont) Lipid transport and utilization Fig. 11 a Capillaries that serve skeletal and cardiac muscle cells, hepatocytes, and adipose cells have a lipoprotein lipase that releases fatty acids and glycerides from chylomicrons. Fatty acids and glycerides move into the interstitium. 38

39. Lipid Metabolism (cont) Lipid transport and utilization move into cells by endocytosis Liver controls all other lipoprotein distribution Fig. 11 b

40. Lipid Metabolism (cont) Dietary fats and cholesterol are the subjects of discussion. Atherosclerosis (plaque buildup in arteries) is directly related to elevated cholesterol levels in the blood. Dietary cholesterol should be less than 300mg / day. Only 20% of circulating cholesterol comes from dietary sources and the rest comes from interconversions from dietary saturated fats since excess lipids are made into acetyl-Co As which are then made into cholesterol. Thus, reducing overall fat intake, especially saturated fats, helps reduce circulating cholesterol levels. Genetic factors, age, and physical conditioning all affect cholesterol levels.

41. Lipid Metabolism (cont) If there is no family history of CAD, a blood cholesterol level below 200 mg / dl is safe (no lifestyle changes needed). A level >240 mg / dl requires major lifestyle changes. A level > 350 mg / dl requires drug therapy. Blood HDL levels may also be measured and the LDL level calculated. High total cholesterol plus elevated LDL (or low HDL) is linked to the development of atherosclerosis. The number of known risk factors for CAD along with blood lipid levels determines the recommendations for lifestyle changes or drug therapy.

42. TOPICS Introduction and Overview Carbohydrate Metabolism Lipid Metabolism Protein Metabolism Nucleic Acid Metabolism Metabolic Interactions Diet and Nutrition Bioenergetics

43. Protein Metabolism Objectives Recall the variety of proteins in the body. Describe the events in amino acid catabolism. Discuss why proteins are not quick energy sources. Discuss protein synthesis.

44. Protein Metabolism Your body contains more than 100,000 different proteins assembled from 20 different amino acid monomers. There is a constant turnover of cellular proteins that occurs by enzymes present in the cytosol. Mitochondria are able to make use of some amino acids in the TCA cycle if carbohydrates and lipids are lacking. Amino acids enter the TCA cycle at different points so the number of reduced carriers generated varies. The average ATP yield per gram of protein is comparable to that for carbohydrates.

45. Protein Metabolism (cont) The first step of amino acid catabolism is the removal of the amino group (–NH2) which requires vitamin B6. If the amino group is transferred to a keto acid molecule (a double bonded oxygen on the middle carbon) to create a new amino acid, the process is called transamination.

46. Protein Metabolism (cont) The amino group may be removed by deamination which also generates an ammonium ion or a toxic ammonia molecule. or NH3

47. Protein Metabolism (cont) Most deamination occurs in the liver which is able to convert the ammonia into nontoxic urea that is excreted in the urine. Fig. 12 c

48. Protein Metabolism (cont) The body is able to synthesize 10 amino acids. There are 10 essential amino acids which must be obtained in the diet of which 2 are nonessential amino acids that may be synthesized but only in insufficient quantities. Even though we do not generally use proteins as energy sources, the diet must have a balance of proteins to supply the amino acids needed for the synthesis of structural and functional proteins. In some third world nations, there are a number of protein deficiency diseases linked to malnutrition. Kwashiorkor and marasmus are two protein deficiency diseases.

49. Protein Metabolism (cont) The amino acids needed for protein synthesis are from dietary sources, transamination reactions, and amination reactions— the addition of an amino group to a short chain carbon molecule. Fig. 13

50. Protein Metabolism (cont) Some genetic disorders arise because DNA does not code for enzymes needed for amino acid metabolism. Phenylketonuria (PKU) is a disorder where the enzyme to convert phenylalanine to tyrosine is defective. Tyrosine is needed to synthesize NE, E, dopamine, and melanin. Nervous system developmental problems will occur in infants and young children if PKU goes undiagnosed. When too much phenylalanine builds up in the blood, it interferes with synthesis of other proteins.