MHS1101 Lecture 3 Cellular Respiration & Metabolism PDF

MHS1101: LEC TURE 3 CELLULAR RESPIRATION & METABOLISM LEARNING OUTCOMES By the end of this lecture you should be able to:  Outline the process of cellular respiration  Outline the two mechanisms of ATP production [high energy bond formation]  Understand the process of oxidation-reduction reactio...

MHS1101: LEC TURE 3 CELLULAR RESPIRATION & METABOLISM LEARNING OUTCOMES By the end of this lecture you should be able to:  Outline the process of cellular respiration  Outline the two mechanisms of ATP production [high energy bond formation]  Understand the process of oxidation-reduction reactions  Describe the role of mitochondria in energy production and metabolism CELLULAR RESPIRATION  conversion of nutrients into form usable by cells for their processes  achieved by production of ATP  catabolic breakdown of nutrients results in energy release  60% lost as heat  40% as APT for cell activities STAGES OF METABOLISM OF ENERGY-CONTAINING NUTRIENTS 1. digestive enzymes break down macromolecules into absorbable forms 2. nutrients are transported to cells & are anabolised or catabolised 3. catabolic pathway of TCA [Krebs] cycle & oxidative phosphorylation  Stages 2 & 3 = cellular respiration A BIT OF REVISION CHEMICAL REACTIONS  cellular respiration involves chemical reactions  Decomposition reactions  breaking bonds between large complex molecules to form smaller fragments that can be absorbed  Hydrolysis  decomposition reaction involving water (elements H2O)  components of water molecule join the new fragments  decomposition reactions collectively known as catabolism  when a covalent bond is broken it releases energy that can be used for work CHEMICAL REACTIONS  Synthesis reactions  assembles smaller molecules into larger molecules (e.g. formation of glycogen)  Dehydration synthesis (or condensation)  opposite of hydrolysis  complex molecule is formed by removing H2O  synthesis of new molecules collectively known as anabolism  creating a chemical bond for those new molecules requires energy  catabolism provides energy for anabolism HIGH-ENERGY BONDS  most chemical reactions that release energy occur in mitochondria  But….most activities requiring energy occur in the cytoplasm  energy must be in a form that can be moved around  high energy bonds (made by enzymes)  covalent bonds  when broken, release energy the cell can use Copyright © McGraw-Hill Education. Permission required for reproduction or display. Figure 3.5 RECALL…ENZYME STRUCTURE & ACTION  enzymes are not consumed by the reactions  one enzyme molecule can consume millions of substrate molecules per minute  temperature, pH & other factors can change enzyme shape & function  can alter ability of enzyme to bind to substrate  enzymes vary in optimum pH ENZYMES  Share 3 main characteristics  specificity  saturation limits  regulation ENZYME STRUCTURE & ACTION Enzyme action  substrate approaches enzyme’s active site  molecules bind together forming enzyme-substrate complex  enzyme-substrate specificity - lock & key  enzyme releases reaction products  enzyme unchanged & can repeat process Figure 2.27 COFACTORS & COENZYMES  ± 2/3 of human enzymes require a nonprotein cofactor  some are inorganic (iron, copper, zinc, magnesium & calcium ions)  some bind to enzyme & induce change in shape, which activates the active site  essential to function  coenzymes - organic cofactors derived from water-soluble vitamins (niacin, riboflavin)  accept electrons from enzyme in one metabolic pathway & transfer them to enzyme in another  e.g. NAD+ [Nicotinamide adenine dinucleotide] ACTION OF A COENZYME  NAD+ transports electrons from one metabolic pathway to another LEARNING OUTCOMES By the end of this lecture you should be able to:  Outline the process of cellular respiration√  Outline the two mechanisms of ATP production [high energy bond formation]  Understand the process of oxidation-reduction reactions  Describe the role of mitochondria in energy production and metabolism HIGH-ENERGY BONDS: ATP  high energy bonds connect a phosphate group (PO43- ) to an organic molecule (phosphorylation)  phosphorylation refers to transfer of phosphate group from one compound to another  term typically used to describe the formation of ATP or addition of free phosphate group to a molecule  carried out by enzymes called kinases  most high energy compounds are derived from nucleotides (e.g. Adenosine diphosphate [ADP], Adenosine triphosphate [ATP]) FORMATION OF HIGH-ENERGY BONDS: ATP  Nitrogenous base (e.g. Adenine)  Add a ribose molecule  Adenosine  Attach a phosphate group (PO43- ) (phosphorylation)  Adenosine monophosphate (AMP)  Attach a phosphate group (PO43- ) (phosphorylation)  Adenosine diphosphate (ADP)  Attach a phosphate group (PO43- ) (phosphorylation)  Adenosine triphosphate (ATP) FORMATION OF HIGH-ENERGY BONDS ATP Figure 2.29 ATP contains adenine, ribose, and three phosphate groups ATP  most important energy-transfer molecule  stores energy gained from exergonic reactions - quickly releases that energy for physiological work  holds energy in covalent bonds  2nd & 3rd phosphate groups have high energy bonds (~)  most energy transfers to & from ATP involve adding or removing 3rd phosphate ATP  formation of ATP [e.g. ADP-ATP]  stores energy  anabolism - uses energy  requires an enzyme – ATP synthase  hydrolysis of ATP [e.g. ATP-ADP]  catabolism - releases energy  requires an enzyme - adenosine triphosphatase (ATPase)  enzyme breaks 3rd high-energy phosphate bond  separates ATP into ADP + Pi + energy LEARNING OUTCOMES By the end of this lecture you should be able to:  Outline the process of cellular respiration√  Outline the two mechanisms of ATP production [high energy bond formation] √  Understand the process of oxidation-reduction reactions  Describe the role of mitochondria in energy production and metabolism OXIDATION-REDUCTION REACTIONS & COENZYMES  Oxidation reactions  gain of oxygen or loss of hydrogen  oxidised substance loses electrons as they are attracted to another substance  step-by-step removal of pairs of hydrogen atoms leaving only CO2  O2 is the final electron acceptor  combines with removed hydrogen atoms at end = H2O  lose electrons (oxidised) - lose energy to other molecules & ultimately to ADP & ATP  gain electrons (reduced) - gain energy OXIDATION-REDUCTION REACTIONS & COENZYMES  reactions are catalysed by enzymes  where H are removed – dehydrogenases  where O are added – oxidases  requires co-enzymes  hydrogen atoms are removed from metabolic intermediates in pairs  two protons & two electrons (2 H + & 2 e− ) at a time  transferred to a coenzyme OXIDATION-REDUCTION REACTIONS & COENZYMES  Two most important:  NAD+ (nicotinamide adenine dinucleotide, derived from niacin (B vitamin)  NAD+ + 2 H → NADH + H +  FAD (flavin adenine dinucleotide, derived from riboflavin)  FAD + 2 H → FADH2  coenzymes become temporary carriers of energy extracted from metabolites  reduced coenzymes with a higher free energy content than before the reaction LEARNING OUTCOMES By the end of this lecture you should be able to:  Outline the process of cellular respiration√  Outline the two mechanisms of ATP production [high energy bond formation] √  Understand the process of oxidation-reduction reactions √  Describe the role of mitochondria in energy production and metabolism MITOCHONDRIAL ENERGY PRODUCTION  double membrane  outer surrounds organelle  inner is folded (cristae)  fluid in the mitochondria – matrix  enzymes in matrix catalyse reactions that produce energy ATP SYNTHESIS Two mechanisms  1. Substrate-level phosphorylation 2. Oxidative phosphorylation SUBSTRATE-LEVEL PHOSPHORYLATION  ATP is formed from ADP by adding a phosphate group  high-energy phosphate groups directly transferred from phosphorylated substrates to ADP  Occurs in:  Glycolysis  Krebs cycle Catalysis Enzyme Enzyme (a) Substrate-level phosphorylation Figure 24.4a ATP PRODUCTION Glycolysis  Glycolysis: splitting Stages of glucose oxidation & ATP synthesis glucose into 2 pyruvates  If ATP demand outpaces Anaerobic fermentation Uses no oxygen O2 supply pyruvate anaerobically ferments to lactate Aerobic respiration Requires oxygen  If enough O2 present aerobic respiration occurs in mitochondria Figure 2.31 ©McGraw-Hill Education. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw-Hill MITOCHONDRIAL ENERGY PRODUCTION OXIDATIVE PHOSPHORYLATION & ELECTRON TRANSPORT SYSTEM  Oxidative phosphorylation  generates ATP  consumes oxygen  coenzymes are required  Electron Transport System  cytochromes pass hydrogen electrons on to oxygen  forms water  as this occurs the system generates ATP OXIDATIVE PHOSPHORYLATION CHEMIOSMOTIC MECHANISMS OF ATP SYNTHESIS  occurs in the mitochondria ▪ carried out by electron transport proteins  hydrogen atoms split into H+ & electrons as they transfer from coenzymes to ETS  electrons are shuttled along inner mitochondrial membrane, losing energy at each step  released energy used to pump H+ into space between inner & outer mitochondrial membranes  Copyright © McGraw-Hill Education. Permission required for reproduction or display. Figure 26.6 OXIDATIVE PHOSPHORYLATION CHEMIOSMOTIC MECHANISMS OF ATP SYNTHESIS  inner membrane permeable to H + only at channel proteins called ATP synthase  creates steep electrochemical gradient for H + across inner mitochondrial membrane ▪ H+ flows through ATP synthase ▪ energy captured & attaches phosphate groups to ADP  NADH is oxidized to NAD+- yields 2.5 ATPs  FADH2 yields 1.5 ATPs when oxidised  Copyright © McGraw-Hill Education. Permission required for reproduction or display. Figure 26.6 Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation Intermembrane space Inner mitochondrial membrane Mitochondrial matrix 2 H+ + FADH2 NADH + (carrying from food) 1 2 ATP synthase FAD H+ NAD+ Electron Transport Chain Electrons are transferred from complex to complex and some of their energy is used to pump protons (H+) into the intermembrane space, creating a proton gradient. ADP + Chemiosmosis ATP synthesis is powered by the flow of H+ back across the inner mitochondrial membrane through ATP synthase. Figure 24.8 THE MITOCHONDRIAL ELECTRON-TRANSPORT CHAIN  oxygen is final electron acceptor  each atom accepts 2 electrons from cytochrome 𝑎3 & 2 protons from mitochondrial matrix forming H2O  primary source of metabolic water H2O  without oxygen, cells produce insufficient ATP to sustain life Figure 26.5 Copyright © McGraw-Hill Education. Permission required for reproduction or display. CARBOHYDRATE METABOLISM  most dietary carbohydrates burned as fuel within hours of absorption  most cells generate high-energy bonds from carbohydrates (especially glucose)  complete catabolism of one glucose molecule each glucose molecule (C6H12O6) produces gain of 36 molecules of ATP  aerobic metabolism – energy production in the mitochondria requires oxygen GLUCOSE METABOLISM  starts in cytosol or cytoplasm of cell with glycolysis ▪ glyco - 'sugar' & lysis - 'breaking' or 'splitting‘ ▪ can take place without O2 [anaerobic, fermentation] ▪ each glucose molecule is broken down into 2 pyruvic acid molecules  pyruvic acid enters the mitochondria  CO2 is removed from each molecule  remainder goes to Tricarboxylic acid (TCA)/Krebs/citric acid cycle ▪ glycolysis uses 2 ATP molecules as energy to fuel this process GLYCOLYSIS ▪ Final products of glycolysis: ▪ 2 x 3-carbon molecules of pyruvic acid ▪ converted to lactic acid if O2 not readily available ▪ enter aerobic pathways if O2 is readily available ▪ 2 NADH + H+ (reduced NAD+) ▪ net gain of 2 ATP ▪ each NADH molecule carries 2 energy electrons ▪ main purpose of NADH is to transport electrons to electron transfer system for further energy extraction GLYCOLYSIS  3 major phases of glycolysis: 1. Sugar activation: glucose is phosphorylated & uses 2 ATP molecules – anabolism stores energy 2. Sugar cleavage: Split into 3-carbon fragments 3. Oxidation & form ATP: removal of hydrogen, and phosphate groups are attached  Substrate level phosphorylation KREBS CYCLE ▪ some of the original energy from glucose is in ATP & NADH ▪ some lost as heat ▪ most of the energy remains in pyruvate Remaining energy in pyruvic acid chemical bonds: ▪ in presence of O2 mitochondria absorb & breakdown pyruvic acid  pyruvic acid enters intermembrane space  carrier protein moves pyruvic acid into the matrix  broken down through Krebs [TCA] cycle KREBS CYCLE  does not directly use O2  enzymatic pathway  main objective of cycle is to use pyruvates to produce more ATP  removes hydrogen atoms from organic molecules & transfers them to co-enzymes  co-enzymes accept electrons from one molecule & give them to another  Co-enzymes:  NAD+ (nicotinamide adenine dinucleotide)  FAD (flavin adenine dinucleotide)  cycle is also source of substances for synthesis of fats & nonessential amino acids KREBS CYCLE ▪ NAD+ & FAD gain electrons (gain energy - reduction)  NADH + (H+)  FADH2  oxidation: loss of electrons is a form of oxidation  oxidised molecules loses electrons & energy KREBS CYCLE ▪ Coenzyme A (involved in metabolism of carbon sugars) joins remaining 2 carbon molecules in pyruvate – forms acetyl-CoA (activated form of acetic acid) ▪ this molecule enters Krebs/citric acid cycle ▪ the 2 carbon atoms combine with 4 carbon atoms - already present in cycle ▪ the 6 carbon atoms form citric acid  broken down & hydrogen removed  electrons passed along coenzymes  energy released performs enzymatic conversion of ADP to ATP THE MITOCHONDRIAL MATRIX REACTIONS Copyright © McGraw-Hill Education. 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Figure 26.4 KREBS CYCLE KREBS CYCLE ▪ next step: substrate-level phosphorylation ▪ ATP is formed from ADP by adding a phosphate group ▪ high-energy phosphate groups directly transferred from phosphorylated substrates to ADP ▪ Phosphoryl (PO3) or phosphate is added to ADP - converts ADP to ATP ▪ the remaining 4 carbon atoms are re-synthesized ▪ leads to another NAD in the cycle to form NADH & FAD, which forms FADH2 ▪ results in 1 ATP, NADH & FADH2 ▪ each cycle uses 1 pyruvate ▪ at end of cycle: 4 ATP - 2 from glycolysis & 2 from Krebs [citric acid] cycle Electron Transport System ▪ final stage of aerobic cellular respiratory cycle ▪ remaining energy from glucose is released via electron transport chain ▪ from Krebs Cycle & glycolysis - 4 ATP, 2NADH & 2FADH2 ▪ in electron transport chain the 2 NADH & 2 FADH2 work with enzymes process called oxidation reduction takes place ▪ NADH & FADH2 (electron donors) contribute their electrons to enzymes (electron acceptors) in cell membrane through electrochemical gradient or path electron transport system ELECTRON TRANSPORT SYSTEM ▪ maximum number of ATP is generated by electron transport system via chemiosmosis ▪ gives cells a total of 32 - 34 ATP ▪ glycolysis takes place in the cytoplasm of a cell ▪ Krebs Cycle & electron transport takes place in mitochondria ▪ oxygen is the most important component of aerobic cellular respiration ▪ Without oxygen, the electrons will remain stagnant in the electron transport chain, putting the production of ATP at halt. ATP GENERATED BY OXIDATION OF GLUCOSE Figure 26.7 Copyright © McGraw-Hill Education. Permission required for reproduction or display. USES OF ATP Figure 2.30 GLYCOLYSIS & ANAEROBIC FERMENTATION Figure 26.3 Copyright © McGraw-Hill Education. Permission required for reproduction or display. ANAEROBIC FERMENTATION  fate of pyruvate depends on oxygen availability  in absence of O2 cells can only generate ATP through glycolysis  gycolysis cannot continue without supply of NAD+  anaerobic fermentation: NADH donates electrons to pyruvate reducing it to lactate & regenerating NAD+  lactate leaves cells that generate it & travel to liver via bloodstream  when O2 becomes available the liver oxidizes it back to pyruvate  O2 required for this is part of reason we breathe more vigorously after exercising (postexercise O2 consumption) LIPID METABOLISM  triglycerides are stored in adipocytes  turnover of lipid molecules every 2-3 weeks  released into bloodstream, transported & either oxidized or redeposited in other fat cells  Lipogenesis - synthesis of fat from other types of molecules  amino acids & sugars used to make fatty acids & glycerol  PGAL can be converted to glycerol  Acetyl-CoA used to make fatty acids LIPID METABOLISM  Lipolysis (catabolism) can be used for TCA cycle  Triglycerides  fatty acids enter mitochondria  beta oxidation - fatty acids broken down into two-carbon fragments that can be used in cycle LIPOGENESIS & LIPOLYSIS PATHWAYS Figure 26.9 Copyright © McGraw-Hill Education. Permission required for reproduction or display. PROTEIN CATABOLISM  rarely used  carbohydrates & lipids used first - proteins as last resort  mitochondria can breakdown amino acids in TCA cycle SUMMARY LEARNING OUTCOMES By the end of this lecture you should be able to:  Outline the process of cellular respiration√  Outline the two mechanisms of ATP production [high energy bond formation] √  Understand the process of oxidation-reduction reactions √  Describe the role of mitochondria in energy production and metabolism √ NEXT LECTURE TISSUES OF THE BODY