Metabolism

1. Chapter 7 Metabolism • by • Norman D. Sossong, MD, PhD • for NSCC: • NTR150 – Spring 2008

2. Metabolism Defined • = the sum total of all the chemical reactions within organisms that enable them to maintain life

3. Energy Sources for Metabolism • The chemical reactions of metabolism require energy • Where does that energy come from? • It comes from the chemical energy in the molecules that are within our cells • Chemical energy is the energy stored in the bonds between atoms of a molecule • How did it get there? • Organisms either ingest the energy-containing molecules or make the molecules that contain the chemical energy • Animals generally ingest the energy-rich molecules • Many plants make the energy-rich molecules through photosynthesis

4. Photosynthesis • By way of review: • Plants containing chlorophyll or similar molecules absorb light (usually from the sun) • With the help of the energy contained in light, the plant cells can take carbon dioxide (CO2) from the air and water (H2O) from the ground and convert it into a carbohydrate, usually glucose (C6H12O6) • The “waste product” of this process is oxygen (O2) • The chemical bonds in the glucose contain the energy absorbed from the light

5. The Laws Governing Energy:The Laws of Thermodynamics • The First Law of Thermodynamics • The “Conservation of Energy” • Energy is neither created nor destroyed (but it may change form) • The Second Law of Thermodynamics • The movement of energy from one place to another is never 100% efficient; there is always some loss of “useful” energy • The waste energy is called “heat”

6. Energy: Fuel for Work • Energy source • Chemical energy in carbohydrates, fat, protein • Food energy to cellular energy • Stage 1: digestion, absorption, transport • Stage 2: breakdown of molecules • Stage 3: transfer of energy to a form cells can use

7. What Is Metabolism? • Catabolism • Reactions that breakdown compounds into small units • Anabolism • Reactions that build complex molecules from smaller ones

8. The Cell is the Metabolic Processing Center • Nucleus* • Cytoplasm • Cytosol + organelles • The organelles • Endoplasmic Reticulum (ER) ± Ribosomes • Golgi Apparatus • Lysosome • Mitochondrion • * Some would classify the nucleus as an organelle

9. Energy Currency in the Body • ATP is the body’s energy currency • ATP = adenosine triphosphate • Form of energy cells use • The useful energy is stored in the phosphate-phosphate bonds • AMP + Pi + E • → ADP + Pi + E • → ATP

10. Energy Currency in the Body • GTP is another form of the body’s energy currency where guanine is used instead of adenine

11. Other Energy Currencies in the Body • NADH, FADH2, & NADPH • Are all high-energy carriers • These must all be converted to ATP (or GTP) to be useful for the body’s various chemical reactions • Analogy: Consider the usefulness of a hundred- or a thousand-dollar bill compared with that of a twenty-dollar bill

12. NADH & FADH2 as Energy Carriers

13. Breakdown and Release of Energy • Extracting energy from carbohydrates • Glycolysis • Pyruvate → Acetyl CoA • Citric Acid Cycle = Krebs Cycle • Electron Transport Chain • End products • Extracting energy from fats • Extracting energy from proteins

14. Extracting Energy from Carbohydrates • Glycolysis • Takes place in cytoplasm • Anaerobic (no oxygen required) • Pathway splits glucose into 2 pyruvates • Glucose (6-C) → 2 Pyruvate (3-C) • Input: 2 ATP • Output: 2NADH + 4 ATP • Net: Output – Input = 2 NADH + 2 ATP • Applies to Glucose  Fructose  Galactose • Results are the same • Note: RBCs use only glycolysis

15. Glycolysis • Note: • Input: 2 ATP • Output: 2NADH + 4 ATP • Net: Output – Input = 2 NADH + 2 ATP

16. Breakdown and Release of Energy • Extracting energy from carbohydrate • Pyruvate (3-C) to Acetyl CoA (2-C) • Aerobic • Releases CO2 • Transfers electrons to NAD • → NADH • Pyruvate can enter mitochondria • but Acetyl CoA cannot leave • Pyruvate to lactate (3-C) • Anaerobic

17. Pyruvate to Acetyl CoA

18. Breakdown and Release of Energy • Extracting energy from carbohydrate • Citric acid cycle = Krebs Cycle • Releases CO2 • 2 for each Acetyl CoA • Produces 1 GTP (like ATP) • Transfers electrons to • 3 NAD → 3 NADH and 1 FAD → 1 FADH2

19. Krebs Cycle or the Citric Acid Cycle

20. Breakdown and Release of Energy • Extracting energy from carbohydrate • Electron transport chain • Accepts electrons from NAD and FAD • Produces large amounts of ATP • i.e. converts NADH & FADH2 into ATP • Produces water • End products of glucose breakdown • ATP, H2O, CO2

21. Breakdown and Release of Energy • Revised (1998) estimates of ATP production in Electron Transport Chain • Originally: NADH → 3 ATP • FADH2→ 2 ATP • Total Glucose Energy = 36-38 ATP • Revised: NADH → 2.5 ATP • FADH2→ 1.5 ATP • Total Glucose Energy = 30-32 ATP

22. Breakdown and Release of Energy • Extracting energy from carbohydrates • Glycolysis • Pyruvate → Acetyl CoA • Citric Acid Cycle = Krebs Cycle • Electron Transport Chain • End products • Extracting energy from fats • Extracting energy from proteins

23. Extracting energy from fat • Split triglycerides into glycerol and fatty acids • Note: this is the reverse of the synthesis of triglycerides

24. Glycerol • A 3-carbon molecule • The cell can convert it to the 3-carbon pyruvate • Pyruvate can be handled exactly the same as it was when the source was glucose • First, convert it to acetyl CoA • Then, use it the way acetyl CoA was used when the source was glucose

25. Recall that Fatty Acids Have a Chain Length of • 4-24 carbons • Always an even number

26. Extracting energy from fat • Beta-oxidation • Breaks apart fatty acids into 2-carbon fragments what are converted to the 2-carbon molecule -acetyl CoA • Transfers electrons to NAD and FAD • The acetyl CoA can be handled just as it was when the source was glucose

27. Extracting energy from fat • Krebs cycle = Citric acid cycle • Acetyl CoA from beta-oxidation enters cycle • Electron transport chain • End products of fat breakdown • ATP, H2O, CO2

28. Summary: Extracting energy from fat • Split triglycerides into glycerol and fatty acids • Beta-oxidation • Breaks apart fatty acids into acetyl CoA • Transfers electrons to NAD and FAD • Citric acid cycle • Acetyl CoA from beta-oxidation enters cycle • Electron transport chain • End products of fat breakdown • ATP, H2O, CO2

29. Breakdown and Release of Energy • Extracting energy from carbohydrates • Glycolysis • Pyruvate → Acetyl CoA • Citric Acid Cycle = Krebs Cycle • Electron Transport Chain • End products • Extracting energy from fats • Extracting energy from proteins

30. Extracting Energy from Proteins • First, split the protein into amino acids • Note the variety of amino acids available

31. The Amino Acids

32. Extracting Energy from Amino Acids • Split off amino group • Converted to urea for excretion

33. Extracting Energy from Amino Acids • Carbon skeleton enters breakdown pathways • Recall that the skeleton for any amino acid will be different than the next • 2-Carbon amino acids can be converted to acetyl CoA • 3-carbon amino acids can be converted to pyruvate • 4-carbon amino acids can be converted to one of the molecules used in the Krebs cyle • Once in the pathway for glucose, the rest proceeds as before • End products • ATP, H2O, CO2, + urea

34. Breakdown and Release of Energy

35. Biosynthesis and Storage • Making carbohydrate (glucose) • Gluconeogenesis • Uses pyruvate, lactate, glycerol, certain amino acids • Storing carbohydrate (glycogen) • Liver, muscle make glycogen from glucose • Making fat (fatty acids) • Lipogenesis • Uses acetyl CoA from fat, amino acids, glucose • Storing fat (triglyceride) • Stored in adipose tissue

36. Biosynthesis and Storage • Making ketone bodies (ketogenesis) • Made from acetyl CoA • Inadequate glucose in cells • Making protein (amino acids) • Amino acid pool supplied from • Diet, protein breakdown, cell synthesis

37. Regulation of Metabolism • May favor either anabolic or catabolic functions • Regulating hormones • Insulin • Glucagon • Cortisol • Epinephrine

38. Special States • Feasting • Excess energy intake from carbohydrate, fat, protein • Promotes storage

39. Special States • Fasting • Inadequate energy intake • Promotes breakdown • Prolonged fasting • Protects body protein as long as possible