Respiration

• Respiration is a catabolic process involving a series of enzyme-catalysed reactions in cells
• Energy-rich respiratory substrates like glucose and fatty acids are broken down during respiration to release energy
• During respiration, high energy C-C, C-H, and C-OH bonds are broken, lower energy bonds are formed, and the remaining energy is used to attach inorganic phosphate to ADP to make ATP
• Some of the energy released during respiration is transferred to chemical energy in ATP (adenosine triphosphate) and some is released as heat energy
• There are two types of respiration: aerobic respiration and anaerobic respiration
• Respiration basics

  
• Aerobic respiration is when a glucose molecule is completely broken down to carbon dioxide and water in a series of reactions. There are four stages:

  • glycolysis
  • link reaction
  • Krebs cycle
  • electron transport chain.

  
• Glycolysis takes place in the cytosol and does not require oxygen
• There are 3 main stages in glycolysis:

  1. Phosphorylation of glucose: 2 ATP molecules provide the phosphate to form a 6C hexose bisphosphate that is unstable with a low activation energy

  2. Splitting of the 6C hexose bisphosphate into two 3C triose phosphate molecules

  3. Oxidation of each triose phosphate to 3C pyruvate through the loss of hydrogen, with ATP produced by substrate level phosphorylation (2 ATP per triose phosphate)
• Glycolysis produces:

  • A net yield of 2 ATP produced by substrate level phosphorylation
  • 2 molecules of reduced NAD (NADH2 or NADH + H+)
  • 2 pyruvates (NAD = nicotinamide adenine dinucleotide)
• First stage - glycolysis

  
• The link reaction takes place in the matrix of mitochondria
• If oxygen is available, pyruvate produced in the cytosol is actively transported into the matrix of the mitochondria
• The link reaction links glycolysis and Krebs cycle
• In the link reaction:

  • 3C pyruvate molecules are converted to 2C acetate (C2H5-) through the loss of a carbon dioxide
  • Carbon dioxide is produced through the action of a decarboxylase enzyme
  • Hydrogen is lost through the action of a dehydrogenase enzyme
  • NAD is reduced by the hydrogen to NADH2
  • Acetate is activated by combining with co-enzyme A to produce acetyl co-enzyme A
• Each molecule of glucose produces two molecules of pyruvate, so the link reaction takes place twice for each glucose molecule
• second stage - Link reaction

  
• Each acetyl co-enzyme A enters the Krebs cycle, which takes place in the matrix of mitochondria
• The Krebs cycle is a series of decarboxylation and dehydrogenation reactions, liberating energy from bonds to provide ATP and reduced NAD (as well as reduced FAD)
• For each molecule of glucose, the Krebs cycle takes place twice, as each molecule produces two molecules of pyruvate
• Key steps in the Krebs cycle:

  • Acetate fragment from acetyl co-enzyme A combines with a 4C compound to produce a 6C compound, regenerating co-enzyme A
  • The 4C compound is regenerated via a series of 6C and 5C intermediates, losing two atoms of carbon in two molecules of CO2 (oxygen from water molecules), known as oxidative decarboxylation
  • Eight hydrogen atoms (four pairs) are lost, reducing NAD and FAD
  • Three molecules of NADH2 and one molecule of FADH2 are produced for each acetyl co-enzyme A molecule
  • One molecule of ATP is produced by substrate level phosphorylation
• Third stage - Krebs cycle

  
• In mitochondria, all molecules of reduced NAD and reduced FAD deliver hydrogen atoms to the electron transport system in the inner mitochondrial membrane as long as oxygen is available
• ATP synthesis by the electron transport chain in mitochondria involves:

  • Source of hydrogen ions: Reduced NAD and reduced FAD
  • Proton pumps and electron carriers located in the inner mitochondrial membrane
  • High concentration of H+ builds up in the inter-membrane space
  • ATP synthetase located in stalked particles on the cristae, where two H+ are needed to produce one ATP
  • Final electron acceptor: Oxygen combines with electrons and protons to form water
  • ATP is produced through oxidative phosphorylation, where H+ ions provide energy for phosphorylation of ADP
• Without oxygen, the reduced NAD and reduced FAD cannot be reoxidised, leading to the inability to pick up more hydrogen atoms, thus under anaerobic conditions, the link reaction and the Krebs cycle cannot take place
• The electron transport chain

  
• Under aerobic conditions, all the NADH2 and FADH2 produced in glycolysis, the link reaction, and the Krebs cycle transport H to the electron transport system
• Each molecule of NADH2 and FADH2 transports two hydrogens to the electron transport chain
• The electrons released as the H+ is passed across the membrane provide energy for the second and third proton pump to pass more H+ across the membrane
• Two H+ are required to synthesize one ATP molecule
• More H+ are pumped into the intermembrane space due to NADH2 than FADH2 because NADH2 delivers the hydrogens to the first proton pump and FADH2 delivers hydrogens to the second pump
• The yield of ATP from one NADH2 is 3 ATP
• The yield of ATP from one FADH2 is 2 ATP
• The yield of ATP from the complete oxidation of one molecule of glucose in aerobic respiration is 38 ATP
• Not all the energy of the glucose molecule is captured in ATP due to heat energy loss, ATP needed to pump pyruvate into the mitochondrial matrix, and some H+ may leak through the inner mitochondrial membrane rather than diffusing through ATP synthetase
• Anaerobic respiration is respiration in the absence of oxygen
• Under anaerobic conditions, only glycolysis can take place
• In animals and some bacteria, reduced NAD transfers hydrogen to pyruvate to form lactate/lactic acid, known as lactic acid fermentation
• Lactic acid production is reversible if oxygen becomes available, and the amount of oxygen needed to remove the lactic acid is called the oxygen debt
• In plants and fungi/yeast, reduced NAD transfers hydrogen to pyruvate to form ethanol and carbon dioxide, known as alcoholic fermentation