Chapter 7 Metabolism •by •Norman D. Sossong, MD, PhD •for NSCC: •NTR150 – Spring 2008 Metabolism Defined • = the sum total of all the chemical reactions within organisms that enable them to maintain life 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 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 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” 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 What Is Metabolism? • Catabolism • Reactions that breakdown compounds into small units • Anabolism • Reactions that build complex molecules from smaller ones 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 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 Energy Currency in the Body • GTP is another form of the body’s energy currency where guanine is used instead of adenine 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 hundredor a thousand-dollar bill compared with that of a twenty-dollar bill NADH & FADH2 as Energy Carriers 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 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 Glycolysis • Note: • Input: 2 ATP • Output: 2NADH + 4 ATP • Net: Output – Input = 2 NADH + 2 ATP 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 Pyruvate to Acetyl CoA 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 Krebs Cycle or the Citric Acid Cycle 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 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 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 Extracting energy from fat • Split triglycerides into glycerol and fatty acids • Note: this is the reverse of the synthesis of triglycerides 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 Recall that Fatty Acids Have a Chain Length of • 4-24 carbons • Always an even number 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 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 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 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 Extracting Energy from Proteins • First, split the protein into amino acids • Note the variety of amino acids available The Amino Acids Extracting Energy from Amino Acids • Split off amino group • Converted to urea for excretion 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 Breakdown and Release of Energy 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 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 Regulation of Metabolism • May favor either anabolic or catabolic functions • Regulating hormones • • • • Insulin Glucagon Cortisol Epinephrine Special States • Feasting • Excess energy intake from carbohydrate, fat, protein • Promotes storage Special States • Fasting • Inadequate energy intake • Promotes breakdown • Prolonged fasting • Protects body protein as long as possible