PHA112- Cellular Respiration 2023.pdf

WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Slide 1 of 34 MPharm PHA112 Essential Biochemistry: Cellular Respiration Dr Steve Darby [email protected] Dale 117 PHA112 Cellular Respiration Respiration WEEK Fundamental Principles Of Anatom...

WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Slide 1 of 34 MPharm PHA112 Essential Biochemistry: Cellular Respiration Dr Steve Darby [email protected] Dale 117 PHA112 Cellular Respiration Respiration WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 By the end of the lecture you should be able to: 1. Describe the process of respiration 2. Understand and explain the process and function of glycolysis and Krebs cycle 3. Understand the difference between aerobic and anaerobic respiration Slide 2 of 34 PHA112 Cellular Respiration WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 3 Why Is Metabolism Clinically Important? Understanding Metabolism Allows Us To Study Fundamental biochemistry of humans Hormone imbalance – impact cellular metabolism MANY Diseases’ impact on metabolism Diabetes – abnormal glucose levels Malnutrition – impacts metabolism Many Therapeutic targets Age – impact on metabolism of cells Musculo-skeletal disorders – metabolism related Faults in enzymes – over or underactive Production of unwanted by-products Inherited diseases – altered from birth Can Impact blood pH Metabolic diseases – glycogen disorders Abnormal Lactate generation – critical clinically Cancer – impact on metabolism of cells We Obtain “Nutrition” From Our Diet WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • Gastrointestinal system will be covered in detail in stage 2 • Food is digested into basic components • Fats / lipids • Carbohydrates • Amino acids • Vitamins and Minerals • Basic components can then be converted into required biomolecules • Proteins, lipids/fats, complex sugars, DNA • Biomolecules can also undergo Metabolism • Metabolism - chemical processes that occur to maintain living systems Slide 4 of 38 PHA112 Cellular Respiration Digestive enzymes WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 5 Glucose is a MAJOR Fuel Source • In our diets, we consume a generous amount of starch and a smaller amount of glycogen. • These complex carbohydrates are converted into simpler carbohydrates for absorption by the intestine and transport in the blood • Glucose is the only fuel that the brain red blood cells use C6H12O6 WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Glucose: The Provider Of Cellular Energy Glucose is the “sugar of life”-multiple purposes Storage: Glycogen and starch Glycogen Starch Cellulose Structural: Cellulose in plants Energy: Principle provider of cellular energy Catabolism of glucose to produce ATP Structural Slide 6 of 34 Storage Glucose Energy ATP PHA112 Catabolism: Breakdown of compounds into simpler molecules to: (i) release energy (ii) provide smaller building blocks Anabolism: Building a more complicated molecule from smaller units (eg, amino acid  proteins) (i) requires energy Cellular Respiration WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Cellular Respiration: Oxidation Of Glucose Cellular Respiration: the breakdown of glucose in many small steps to make ATP Slide 7 of 34 - Breakdown a “large sugar” molecules into smaller ones - breaking bonds and moving electrons from one molecule to another - electrons “carry energy” - energy is used to make ATP – ATP = Adenosine Tri-Phosphate Glucose + Oxygen  Carbon + Water + Energy dioxide C6H1206 PHA112 + 6O2  6CO2 + Cellular Respiration H2O + ATP Oxidation and Reduction WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Slide 8 of 34 Key processes in cellular respiration PHA112 Cellular Respiration Redox Reaction WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Slide 9 of 34 Glucose is oxidised and oxygen is reduced Redox reaction PHA112 Cellular Respiration Movement Of Electrons In Biology WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • Electrons can not move alone in the cells • Electrons can move as part of a hydrogen atom • Move hydrogen atom = move electron • Consider: H H+ + e- Slide 10 of 34 Hydrogen Hydride 1H One proton One proton . H Two electron One electron PHA112 H: Cellular Respiration or H:- Electron carriers WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • High energy electrons produced during the breakdown of glucose • Certain molecules are particularly effective in accepting or donating these electrons, these are therefore called electron carriers • NAD – Nicotinamide Adenine Dinucleotide • FAD – Flavin Adenine Dinucleotide • NAD+ coenzyme and FAD cofactor are very good at carrying electrons and donating them to target molecules • Once the energy is harvested from electrons….. • oxygen is very good at accepting electrons to forms water as end product of respiration • O2 + 4H+ +4e-  2H2O Slide 11 of 34 PHA112 Cellular Respiration Electron Carriers: NAD+ WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • NAD+ is a coenzyme which regulates the activity of the enzyme it is bound to • Co-enzymes can move around the body • Derived from the vitamin nicotinic acid/niacin • NAD+ is the oxidised form • NAD+ can accept two electrons from two hydrogen atoms to be reduced to NADH • NAD+ + 2H+ +2e-  NADH + H+ • One hydrogen is transferred as a hydride ion: H- and the second liberated in solution Slide 12 of 34 Ribose phosphate Ribose Nicotinamide Adenine dinucleotide (NAD+) PHA112 Cellular Respiration Example of NADH Production WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Formation of oxaloacetate from malate in Krebs cycle Released as H+ Added as Slide 13 of 34 NADH contains high energy electrons H- Used to make ATP in the electron transport chain (ETC) PHA112 Cellular Respiration Electron Carriers: FAD WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • FAD is a cofactor which binds strongly to an enzyme • FAD is synthesised from vitamin B2 or riboflavin • FAD is the oxidised form • FAD can accept two hydrogens and two electrons to be reduced to FADH2 • FAD + 2H+ +2e-  FADH2 Slide 14 of 34 Flavin Adenine dinucleotide (FAD) PHA112 Cellular Respiration WEEK Example of FADH2 production Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Slide 15 of 34 Formation of fumarate from succinate in Krebs cycle NADH contains high energy electrons We will use this to make ATP in the electron transport chain (ETC) PHA112 Cellular Respiration WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 ATP Is the Universal Currency of Free Energy in Biological Systems • Energy required for muscle contraction, generating nerve impulses • MANY MANY cells processes require energy – obtain this from ATP • Hydrolysis of ATP provides energy Slide 16 of 34 ATP PHA112 Cellular Respiration Hydrolysis of ATP WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 ATP is structurally unstable due to the repulsion between ionised oxygen atoms which are all in close proximity Hydrolysis of terminal phosphate group stabilises ATP and the process “releases energy” ∆Go is negative: (i) Reactant has more energy than the product (ii) Free energy is released (iii) Product is more stable (iv) Favourable reaction ATP Slide 17 of 34 H2O ATPase PHA112 ADP + Pi ∆Go = -30.5kJ mol-1 Cellular Respiration Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 WEEK Slide 18 of 38 ATPADPAMP PHA112 Cellular Respiration Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 WEEK 19 Overview Of Respiration WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 The complete oxidation of glucose proceeds in four key stages: 1. Glycolysis 2. Pyruvate processing (connects glycolysis to next stage) 3. Citric Acid Cycle (aka Krebs Cycle) 4. Electron transport chain Slide 20 of 34 Cytoplasm PHA112 Mitochondria Cellular Respiration Glycolysis Is The First Stage Of Energy Production WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • Glycolysis uses GLUCOSE from our diet as a starting material • Glucose is converted to a chemical called PYRUVATE • This has 10 chemical reactions all controlled by enzymes • The final product is then passed on to the next stage of respiration Slide 21 of 38 PHA112 Cellular Respiration WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 22 Glycolysis Overview • 2 Major Stages: • Stage 1 – Preparation stage, this stage needs energy to proceed and requires ATP • Stage 2 – Cyclic rings are converted to smaller 3 carbon products – Providing products for the next step of metabolism - Pyruvate – ATP is harvested back during this stage Stage 1 of Glycolysis WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Slide 23 of 34 Preparatory/investment phase: uses ATP Isomers PHA112 Cellular Respiration Second Phase Of Glycolysis WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 DHAP converted to G3P hence 2xG3P Payoff phase: make ATP and NADH Substrate level phosphorylation: Make ATP by transferring phosphate from a substrate Slide 24 of 34 PHA112 Cellular Respiration WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 25 ATP Generation from Stage 2 of Glycolysis • PEP converted to pyruvate • Phosphate group returned back to ADP  ATP Glycolysis Summary WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Glycolysis converts glucose to pyruvate 1. 10 step biochemical pathway 2. 2 NADH are produced by reduction of NAD+ 3. NET production of 2 ATP molecules by substrate level phosphorylation 4. 2 molecules of pyruvate are produced 5. Occurs in the cytoplasm Slide 26 of 34 1 2 3 3 4 PHA112 Cellular Respiration Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 WEEK 27 Sugars Can Be Bound Together Glycogen Starch WEEK Feeder Pathway For Glycolysis Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Slide 28 of 34 Entry of glycogen, starch, disaccharide's into the preparatory stage of glycolysis You can now see how they all feed into ATP generation STAGE 2 – ATP producing PHA112 Cellular Respiration WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 29 Metabolism and Lactose Intolerance • Lactose is found in milk and can be converted to galactose and glucose • If a person lacks or has a lower level of the enzyme “lactase” then this conversion does not occur and lactose remain undigested • So what happens next? BACTERIA in the gut ferment the undigested lactose – Gas – Bloating / pain – Diarrhoea WEEK NAD+ Regeneration Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • For glycolysis to continue NADH must be recycled back to NAD+ • Aerobic respiration - Occurs when oxygen is available as the final electron acceptor • Anaerobic respiration (or fermentation) occurs when oxygen is not available; an organic molecule is the final electron acceptor Slide 30 of 34 Fermentation Aerobic Respiration Anaerobic Respiration PHA112 Cellular Respiration In The Absence Of Oxygen - Anaerobic Respiration Occurs WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • In absence of O2 Pyruvate is reduced to form Lactic acid / Lactate • The transferred electrons oxidise NADH back to NAD+ • This reaction is catalysed by the enzyme Lactate dehydrogenase (LDH) • Lactic acid is converted back into glucose in the liver via the cori cycle • HUGE implications - High lactate levels cause muscle cramps and pain • VERY high lactate can be life threatening – many diseases implicated Slide 31 of 34 PHA112 Cellular Respiration WEEK Cori Cycle (aka Lactic Acid Cycle) Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Slide 32 of 34 ATP • Lactate produced during anaerobic glycolysis is transported to the liver and converted to glucose • This process requires ATP • The glucose is then supplied back to the muscle • If glucose is not required store as glycogen PHA112 Cellular Respiration When The Body Lacks Fuel It Can Make Its Own Glucose Supply WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 33 • The Heart and Brain cannot be starved of fuel • Pyruvate can be converted back • This is a process called Gluconeogenesis • (glucose-new-formation) • Occurs in the liver • To be discussed more in diabetes lectures Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 WEEK 34 WHAT NEXT? Oxidation of Pyruvate WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • In the presence of oxygen, pyruvate is oxidised to acetyl CoA in the mitochondria • Pyruvate moves easily through the porous outer mitochondrion membrane where it encounters Pyruvate Dehydrogenase (PDH) Slide 35 of 34 (PDH) PHA112 Cellular Respiration WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 36 Acetyl CoA Then Enters - The Citric Acid Cycle • Glycolysis produces Pyruvate • Pyruvate is converted to Acetyl CoA • Acetyl CoA now progresses to the next part of metabolism • The CITRIC ACID CYCLE – Also known as Tricarboxylic acid (TCA) cycle – Krebs Cycle • Glucose will continuously be converted to pyruvate via glycolysis to feed this stage Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 WEEK 37 Citric Acid Cycle Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 WEEK 38 Citric Acid Cycle WEEK Breakdown Of One Glucose: So Far.. Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 Reaction Location Net yield of key molecules Glycolysis Cytoplasm 2 ATP 2 NADH Pyruvate oxidation Mitochondrial intermembrane space 2 NADH Krebs cycle Mitochondrial matrix 2 ATP 2 FADH2 6 NADH • Only 4 ATP’s produced so far…. • Complete breakdown of glucose produces ∼30 ATP’s • All remaining ATPs are produced via the electron transport chain Slide 39 of 34 PHA112 Cellular Respiration Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 WEEK 40 Electron Transfer System WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • Metabolism of Glucose 41 • Glycolysis • Citric Acid Cycle • Electron Transfer • ALL work together to provide ATP (currency of energy) • How Much ATP From 1 Molecule Of Glucose? • Glycolysis = 2 • Citric acid = 2 • Electron Transfer = 26 • Total = 30 ATP Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 WEEK 42 WEEK Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 • Metabolism is a VERY complex area of biochemistry • We will introduce more in later stages of the programme Slide 43 of 38 PHA112 Cellular Respiration Fundamental Principles Of Anatomy, Physiology, Pharmacology And Microbiology 11 WEEK 44 ANY Questions ?