Metabolism Chapter 7 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 (CO 2 ) from the air and water (H 2 O) from the ground and convert it into a carbohydrate, usually glucose (C 6 H 12 O 6 ) The “waste product” of this process is oxygen (O 2 ) 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

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

The Cell’s Structures & Functions

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 + P i + E → ADP + P i + E → ATP

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 + P i + E → ADP + P i + 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, FADH 2, & 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

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 CO 2 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 CO 2 2 for each Acetyl CoA Produces 1 GTP (like ATP) Transfers electrons to 3 NAD → 3 NADH and 1 FAD → 1 FADH 2

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 & FADH 2 into ATP Produces water End products of glucose breakdown ATP, H 2 O, CO 2

The Electron Transport Chain

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 = ATP Revised:NADH → 2.5 ATP FADH2 → 1.5 ATP Total Glucose Energy = ATP

Total ATP from Glucose

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, H 2 O, CO 2

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, H 2 O, CO 2

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

The 20 Common 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, H 2 O, CO 2, + 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