Metabolism: Transformations and Interactions

1. Metabolism: Transformations and Interactions Chapter 7

2. Introduction • Energy • Heat for temperature maintenance • Mechanical to move muscles • Electrical for nerve impulses • Chemical- how energy is stored in food and body (ATP) • Metabolism • Release of energy, water, and carbon dioxide

3. Chemical Reactions in the Body • Energy metabolism after absorption • How body obtains & uses energy from food • Where does a lot of metabolism happen? • In Cells, liver cells especially • Anabolism – condensation rxn’s • Requires energy to build body’s compounds • Catabolism – hydrolysis rxn’s • Releases energy when compounds are broken down

5. A Typical Cell

6. Inside the cell membrane lies the cytoplasm, a lattice-type structure that supports and controls the movement of the cell’s structures. A protein-rich jelly-like fluid called cytosol fills the spaces within the lattice. The cytosol contains the enzymes involved in glycolysis.a A separate inner membrane encloses the cell’s nucleus. Inside the nucleus are The chromosomes, Which contain the genetic material DNA. Known as the “powerhouses” of the cells, the mitochondria are intricately folded membranes that house all the enzymes involved in the conversion of pyruvate to acetyl CoA, fatty acid oxidation, the TCA cycle, and the electron transport chain. This network of membranes is known as smooth endoplasmic reticulum—the site of lipid synthesis. Rough endoplasmic reticulum is dotted with ribosomes—the site of protein synthesis. A membrane encloses each cell’s contents and regulates the passage of molecules in and out of the cell.

7. Chemical Reactions in the Body

8. ANABOLIC REACTIONS Glycogen Triglycerides Protein Uses energy Uses energy Uses energy + Glucose Glycerol + Fatty acids Amino acids + Amino acids Glucose Anabolic reactions include the making of glycogen, triglycerides, and protein; these reactions require differing amounts of energy. CATABOLIC REACTIONS Glycogen Triglycerides Protein Glucose Glycerol Amino acids Fatty acids Yields energy Yields energy Yields energy Yields energy Catabolic reactions include the breakdown of glycogen, triglycerides, and protein; the further catabolism of glucose, glycerol, fatty acids, and amino acids releases differing amounts of energy. Much of the energy released is captured in the bonds of adenosine triphosphate (ATP).

9. Metabolism in the Body • Transfer of energy in reactions – ATP • Released during breakdown of glucose, fatty acids, and amino acids • Form of phosphate groups • Negative charge – vulnerable to hydrolysis • Provides energy for all cell activities • Coupled reactions • Efficiency • Heat loss

10. Adenosine Triphosphate (ATP) + Adenosine 3 phosphate groups

11. Capture/Release of Energy by ATP

12. Energy is released when a high-energy phosphate bond in ATP is broken. Just as a battery can be used to provide energy for a variety of uses, the energy from ATP can be used to do most of the body’s work—contract muscles, transport compounds, make new molecules, and more. With the loss of a phosphate group, high-energy ATP (charged battery) becomes low-energy ADP (used battery). ATP ADP 1 1 ATP breakdown ATP ADP + P Energy is required when a phosphate group is attached to ADP, making ATP. Just as a used battery needs energy from an electrical outlet to get recharged, ADP (used battery) needs energy from the breakdown of carbohydrate, fat, and protein to make ATP (recharged battery). 2 ATP synthesis 2

13. Helpers in Metabolic Rxn’s • Enzymes • Facilitators of metabolic reactions • Coenzymes • Organic • Associate with enzymes • Without coenzyme, an enzyme cannot function

14. II. Break Down Nutri. for Energy • Digestion • Carbohydrates into glucose & other monosaccharides • Fats (triglycerides) into glycerol and fatty acids • Proteins into amino acids • Digestion Products: molecules of glucose, glycerol, amino acids, and fatty acids • Catabolism • Carbon, nitrogen, oxygen, hydrogen

15. Nutrient Breakdown for Energy • Two energy-releasing compounds headed for TCA cycle and electron transport chain • Pyruvate • 3-carbon structure • Can be used to make glucose • Acetyl CoA • 2-carbon structure • Cannot be used to make glucose

16. Acetate (coenzyme A missing) Pyruvate

17. Breaking Down Nutrients for Energy

18. 5 3 2 1 5 4 3 2 1 4 Protein Fat Carbohydrate Fatty acids Amino acids Glucose Glycerol Pyruvate All of the energy-yielding nutrients— protein, carbohydrate, and fat—can be broken down to acetyl CoA. 1 Acetyl CoA Acetyl CoA can enter the TCA cycle. TCA cycle Most of the reactions above release hydrogen atoms with their electrons, which are carried by coenzymes to the electron transport chain. Electron transport chain ATP is synthesized. 4 5 Hydrogen atoms react with oxygen to produce water. ATP Water

19. Glucose has 6 carbons

20. Glycerol has 3 carbons

21. Amino acids have varying no.’s of carbons

22. Breaking Down Nutrients for Energy – Glucose • Glucose to pyruvate • Glycolysis • For short energy bursts and TCA cycle prep • 1 glucose yields 2 pyruvate • Hydrogen atoms carried to electron transport chain • Pyruvate can be converted back to glucose • Liver cells and kidneys (to some extent)

23. Glucose to PyruvateGlycolysis • Fructose and galactose enter same pathway glucose is on • Needs ATP for jump start • file:///E:/Media/Animations/chapter7/0705.html

24. Glycolysis

25. Glucose A little ATP is used to start glycolysis. Uses energy (ATP) Galactose and fructose enter glycolysis at different places, but all continue on the same pathway. Uses energy (ATP) In a series of reactions, the 6-carbon glucose is converted to other 6-carbon compounds, which eventually split into two interchangeable 3-carbon compounds. Coenzyme Coenzyme To Electron Transport Chain A little ATP is produced, and coenzymes carry the hydrogens and their electrons to the electron transport chain. Coenzyme Coenzyme Yields energy (ATP) These 3-carbon compounds go through a series of conversions, producing another 3-carbon compound, each slightly different. NOTE: These arrows point down indicating the breakdown of glucose to pyruvate during energy metabolism. (Alternatively, the arrows could point up indicating the making of glucose from pyruvate, but that is not the focus of this discussion.) Eventually, the 3-carbon compounds are converted to pyruvate. Glycolysis of one molecule of glucose produces two molecules of pyruvate. Yields energy (ATP) 2 Pyruvate

26. Breaking Down Glucose for Energy • Pyruvate’s options • Quick energy needs – anaerobic • Pyruvate-to-lactate or back to glucose • Slower energy needs – aerobic • Pyruvate-to-acetyl CoA (irreversible to glucose)

27. Breaking Down Glucose for Anaerobic Energy • Pyruvate conversion to lactate • Pyruvate accepts hydrogens • Occurs during high-intensity exercise, has limited minutes • Produces ATP quickly when too few mitochondria or low oxygen • Accumulation of lactate in muscles from rapid glycolysis • Liver’s Cori cycle- lactate back to glucose

28. Breaking Down Glucose for Anaerobic Energy

29. In the liver: In the muscle: Glucose returns to the muscles Glucose Glucose Coenzyme Coenzyme Uses energy (ATP) Yields energy (ATP) Coenzyme Coenzyme Coenzyme Coenzyme Lactate travels to the liver 2 Pyruvate 2 Lactate 2 Lactate Liver enzymes can convert lactate to glucose, but this reaction requires energy. The process of converting lactate from the muscles to glucose in the liver that can be returned to the muscles is known as the Cori cycle. Working muscles break down most of their glucose molecules anaerobically to pyruvate. If the cells lack sufficient mitochondria or in the absence of sufficient oxygen, pyruvate can accept the hydrogens from glucose breakdown and become lactate. This conversion frees the coenzymes so that glycolysis can continue. NOTE: Other figures in this chapter focus narrowly on the carbons of pyruvate. Its oxygen group is included in this figure to more clearly illustrate this reaction. See definitions for the chemical structures of pyruvate and lactate.

30. In the liver: Glucose Uses energy (ATP) 2 Lactate Cori Cycle Stepped Art

31. Breaking Down Glucosefor AEROBIC Energy • Pyruvate-to-Acetyl CoA • Pyruvate enters mitochondria of cell • Carbon removed – becomes carbon dioxide • 2-carbon compound joins with CoA becoming acetyl CoA – irreversible

32. Breaking Down Glucosefor AEROBIC Energy

33. 2 Pyruvate Coenzyme Coenzyme To Electron Transport Chain Coenzyme 2 CoA Coenzyme 2 Carbon dioxide CoA CoA 2 Acetyl CoA To TCA Cycle Each pyruvate loses a carbon as carbon dioxide and picks up a molecule of CoA, becoming acetyl CoA. The arrow goes only one way (down) because the step is not reversible.

34. Breaking Down Glucose for AEROBIC Energy… now or later • Acetyl CoA’s options – 2 functions • Synthesize fats when ATP is abundant • Any molecule that can make acetyl CoA can make fat (glucose, glycerol, fatty/amino acids) • Acetyl CoA itself can only make fatty acids • Generate more ATP through TCA cycle than glycolysis • Hydrogens – electron transport chain

35. Paths of Pyruvate and Acetyl CoA Glucose Glycerol Amino acids (glucogenic) Pyruvate Lactate Amino acids (ketogenic) Fatty acids Acetyl CoA NOTE: Amino acids that can be used to make glucose are called glucogenic; amino acids that are converted to acetyl CoA are called ketogenic.

36. Summary of Glucose to Acetyl CoA

37. Glucose Coenzyme Coenzyme Coenzyme To Electron Transport Chain Coenzyme 2 Pyruvate Coenzyme Coenzyme 2 CoA To Electron Transport Chain Coenzyme Coenzyme 2 Carbon dioxide CoA CoA IN SUMMARY 1 glucose yields 2 pyruvate, which yield 2 acetyl CoA. 2 Acetyl CoA To TCA Cycle

38. Breaking Down Glycerol and Fatty Acids from TG for Energy • Glycerol into pyruvate • Glycerol can be converted to • Glucose • Pyruvate • Fatty acids into Acetyl CoA • Fatty acid oxidation • 2-carbon units at a time join with CoA • Hydrogens and electrons carried to electron transport chain

39. Glycerol Pyruvate

40. Breaking Down Glycerol and Fatty Acids from TG for Energy • Fatty Acid to Acetyl CoA • 2 fatty acids are snapped off at a time to combine with CoA to make Acetyl CoA (oxidation rxn) • file:///E:/Media/Animations/chapter7/0710.html • 16-carbon fatty acid yields 8 Acetyl CoA

41. Breaking Down Glycerol and Fatty Acidsfor Energy

42. Fatty Acid to Acetyl CoA

43. Breaking Down Glycerol and Fatty Acidsfor Energy

44. Breaking Down Glycerol and Fatty Acidsfor Energy Fatty acids Glycerol 18 C 18 C 18 C 54 C 3 C A typical triglyceride contains only one small molecule of glycerol (3 C) but has three fatty acids (each commonly 16 C or 18 C, or about 48 C to 54 C in total). Only the glycerol portion of a triglyceride can yield glucose.

45. Fats Enter the Energy Pathway Glucose Fat (triglycerides) Glycerol Fatty acids Pyruvate CoA To Electron Transport Chain Carbon dioxide CoA Coenzyme Coenzyme CoA Acetyl CoA To TCA Cycle Glycerol enters the glycolysis pathway about midway between glucose and pyruvate and can be converted to either. Fatty acids are broken down into 2-carbon fragments that combine with CoA to form acetyl CoA (shown in Figure 7-11). IN SUMMARY A 16-carbon fatty acid yields 8 acetyl CoA.

46. FatsEnter the Energy Pathway • Product of 16-C fatty acid is 8 Acetyl CoA for now or later file:///E:/Media/Animations/chapter7/0711.html

47. Breaking Down Amino Acids for Energy • Amino acids into glucose, then energy • Several entry points in energy pathway • Converted to pyruvate (glucogenic) • Converted to acetyl CoA (ketogenic) • Enter TCA cycle directly (glucogenic) • Amino acids-to-glucose

48. Breaking Down Amino Acids for Energy Deamination of amino acids (lose amino N-group)

49. Breaking Down Amino Acids for Energy

50. Amino acids Most amino acids can be used to synthesize glucose; they are glucogenic. Pyruvate CoA Coenzyme To electron transport chain Coenzyme Carbon dioxide Some amino acids are converted directly to acetyl CoA; they are ketogenic. CoA Acetyl CoA Some amino acids can enter the TCA cycle directly; they are glucogenic. To TCA Cycle NOTE: Deamination and the synthesis of urea are discussed and illustrated in Chapter 6. The arrows from pyruvate and the TCA cycle to amino acids are possible only for nonessential amino acids; remember, the body cannot make essential amino acids.