Chapter 5 Cell Respiration & Metabolism Remon Wahba, MD

Chapter 5 Outline Glycolysis Lactic Acid Pathway Aerobic Respiration Fat & Protein Metabolism 5-2

Metabolism All reactions in the body that involve Energy Transformations 5-3

Metabolism Catabolism Anabolism Divided into 2 categories: Breaking down of molecules to Release Energy Is primary source of energy for making ATP Anabolism Formation (synthesis) of larger molecules Requires Energy Source of body’s large energy-storage compounds

Metabolism continued 5-4

Glycolysis 5-4

Glycolysis Breaking down of Glucose Molecules Does not require Oxygen (Anaerobic) Occurs in the Cytoplasm Glucose Molecules split into 2 Molecules of Pyruvate Small amount of Energy is liberated 2 ATP ( Adenosine Tri Phosphate) 2 NADH ( Nicotinamide Adenine Di Nucleotide

Glycolysis (cont) Glycolysis is Exergonic Produces net of 2ATPs & 2NADHs However, glucose must be activated with 2ATPs (phosphorylation) before energy can be obtained Phosphorylation traps glucose inside cell So 2 ATPs are used & 4 ATPs are produced (net gain of 2 ATP) 5-6

Glycolysis (cont) Fig 5.2 5-7

Lactic Acid Pathway For Glycolysis to continue, NADHs produced need to give its Hs away In absence of O2, NADH gives its Hs to pyruvate creating Lactic acid (Anaerobic Respiration) In the presence of O2, NADH gives its Hs to O2 forming Water (Aerobic Respiration) 5-8

Lactic Acid Pathway

Lactic Acid Pathway continued Also called Lactic Acid Fermentation Occurs in Skeletal & Heart muscles when oxygen supply falls below critical level During Heavy Exercise or Vascular Blockage Occurs in RBCs Don't have mitochondria Use only lactic acid pathway 5-9

Glycogenesis & Glycogenolysis For osmotic reasons cells can't store many free Glucose molecules Glycogenesis Storage of Glucose as Glycogen Skeletal Muscles & Liver store lots of Glycogen Glycogenolysis Breaking down of Glycogen to release Glucose as glucose 6-phosphate Phosphate groups trap Glucose molecules inside cells 5-10

Glycogenesis & Glycogenolysis continued Skeletal muscles use trapped glucose-6-phosphate for their own energy needs Liver has glucose-6-phosphatase that removes phosphate groups So glucose can be released into the blood stream to be used by All Body Cells 5-11

Cori Cycle Some Lactic Acid produced in skeletal muscle goes to Liver Where it is converted back into Pyruvate then to Glucose & Glycogen This process is called: Gluconeogenesis (Formation of new glucose) 5-12

Cori Cycle Helps to: Restore Skeletal Muscle Glycogen which was consumed during exercise Remove Lactic Acid from the Blood

Cori Cycle

Aerobic Respiration 5-13

Aerobic Respiration Occurs in the Mitochondria Requires the presence of Oxygen (aerobic) Pyruvates are broken down and CO2 is produced Large amount of Energy is Produced (34-36 ATP)

Aerobic Respiration Begins when Pyruvate formed by Glycolysis enters Mitochondria C02 is removed from Pyruvate forming Acetyl CoA (Coenzyme A is a carrier for acetic acid) C02 goes to lungs to be excreted Energy in Acetyl CoA is extracted during Aerobic respiration in mitochondria 5-14

Aerobic Respiration

Krebs Cycle Begins with Acetyl CoA combins with Oxaloacetic Acid to form Citric Acid In a series of reactions Citric Acid is converted back to Oxaloacetic Acid to complete the pathway Two ATP molecules are produced in the Krebs Cycle from every glucose molecule Large amount of ATP is produced by Electron Transport Chain (ETC) from NADH and FADH

Electron Transport Chain Chain of molecules in inner mitochondrial membrane Molecules undergo Oxidation / Reduction reactions and Energy is released. Energy released is used to synthesize ATP by Oxidative Phosphorylation O2 is the Last electron acceptor and water is formed

Krebs Cycle

Krebs Cycle continued Fig 5.8 5-17

Function of Oxygen Allows Electron Transport to continue by acting as The Final Electron Acceptor O2 accepts these electrons & combines with 4H+s to form 2 water molecules O2 + 4 e- + 4 H+  2 H20 In the absence of O2, the Kreb’s cycle would stop and Respiration becomes Anaerobic

ATP Formation ATP can be made by 2 ways: Direct (substrate-level) phosphorylation Where ATP is generated when bonds break 2 ATPs in Glycolysis are made this way 2 ATPs / glucose in Kreb's made this way Oxidative Phosphorylation Where ATP is generated by ETC (Electron Transport Chain) 30 - 32 ATPs are produced this way (some are used to pump ATP out of the Mitochondria) 5-23

Net Production of ATP 2 from Glycolysis 2 from Direct Phosphorylation in Krebs Cycle 26 from Oxidative Phosphorylation in ETC A total of 30 ATPs are produced from each Glucose Molecule

Fat & Protein Metabolism 5-28

Fats & Proteins as Energy Sources Fats are hydrolyzed to Glycerol & Fatty acids These can be modified to run through Kreb's Proteins are broken down to Amino Acids Which can be Deaminated & run through Kreb's These pathways can be used to interconvert Carbohydrates, Fats, & Proteins 5-29

Fats Glycogen Protein Glucose Amino acids Carbon backbone NH3 Urea (waste) Fatty acids Glycerol Pyruvate Citric acid cycle Acetyl CoA Electron transport system Preparatory step (2) many Figure 3.30

Energy Storage When more energy is taken in than consumed, ATP synthesis is inhibited Glucose is converted into: Glycogen & Fat 5-30

Acetyl CoA Is a common Substrate for energy & synthetic pathways Fig 5.12 5-31

Fat Synthesis (Lipogenesis) Acetyl CoAs Can be linked together to form fatty acids Fatty acids + glycerol = Fat (Triglycerides) Occurs mainly in: Adipose Tissue & Liver 5-32

Fat Synthesis (Lipogenesis) Fat is a major form of energy storage in body Yields 9 kilocalories/gram Carbs & proteins yield only 4 Kilocalories/g Most Energy stored in the body is in the form of Triglycerides

Lipolysis Is breakdown of fat into Fatty Acids & Glycerol Via hydrolysis by Lipase Acetyl CoAs from free fatty acids serve as major energy source for many tissues 5-33

Ketone Bodies Triglycerides are continually broken down & resynthesized Ensures blood will contain fatty acids for Aerobic Respiration During Fasting, Severe Dieting & in Severe Diabetes large amount of fat is broken down Causes high levels of Free Fatty Acids Some are converted by the Liver into ketone bodies Give breath an Acetone smell 5-36

Amino Acid Metabolism Nitrogen (N) ingested primarily as Protein Which is used in body as Amino Acids Excess is excreted mainly as Urea 5-37

Nitrogen (N) Balance Nitrogen balance = N ingested Vs. N excreted Positive N balance: N ingested is more than excreted Negative N balance: N ingested is less than excreted In Healthy Adults: Amount of N excreted = Amount ingested 5-38

Nitrogen (N) Balance Carbs (Gluconeogenesis) Fat (Lipogenesis) Excess amino acids are not stored in the body Can be converted into: Carbs (Gluconeogenesis) Fat (Lipogenesis)

Essential & Non-essential Amino Acids 20 amino acids used to build proteins: 12 can be produced by body (Non-essential) 8 must come from diet (Essential Amino Acids) Proteins of Animal Origin are rich in Essential Amino Acids 5-39

Essential & Non-essential Amino Acids

Transamination Transfer of Amine Group from one Amino Acid to create another one New Amino Acids can be produced Addition of -NH2 group to pyruvate or Kreb's cycle Acids (Keto Acids) to make a new amino acid Catalyzed by Transaminase 5-40

Oxidative Deamination Is process by which excess Amino Acids are eliminated -NH2 (Amine group) is removed from Glutamic acid, forming keto acid & Ammonia Ammonia is converted to urea & excreted Keto acid goes to Kreb’s or to Fat or Glucose 5-42

Gluconeogenesis The formation of new Glucose from Non- Carbohydrate molecules. During Prolonged Fasting most of Blood Glucose is produced in the Liver by Gluconeogenesis

Gluconeogenesis New glucose can be formed from: Amino Acids Amino Acids are converted to Keto Acids, then Pyruvate, then Glucose Glycerol From the breakdown of Lipids Lactate Lactates are first converted into Pyruvates then to Glucose (Cori Cycle)

Uses of Different Energy Sources Different cells have different preferred energy substrates Brain uses glucose as its major source of Energy 5-44

Uses of Different Energy Sources

Terms to Remember Glycolysis Glycogenesis Glycogenolysis Breakdown of Glucose into 2 Pyrovate Glycogenesis Formation of Glycogen from Glucose Glycogenolysis Breaking down of Glycogen to release Glucose Gluconeogenesis Formation of Glucose from Noncarbohydrate

Terms to Remember Lipolysis Lipogenesis Ketogenesis: Breakdown of Lipids into Fatty Acids & Glycerol Lipogenesis Formation of Lipids for storage Ketogenesis: Formation of Ketone Bodies from Fatty Acids Occurs in the Liver