Cellular Respiration (FZC021) PDF

FZC021: Biological Sciences Cellular Respiration Wesley Ward ([email protected]) Where opportunity creates success Learning Outcomes Mitochondrial Structure and Function: Students will gain an understanding of the structure and function of mitochondria, the cellular organelle responsible f...

FZC021: Biological Sciences Cellular Respiration Wesley Ward ([email protected]) Where opportunity creates success Learning Outcomes Mitochondrial Structure and Function: Students will gain an understanding of the structure and function of mitochondria, the cellular organelle responsible for energy production. Energy-Related Molecules: This lecture will provide an overview of key energy-carrying molecules, such as ATP, NADH, and FADH2, and their roles in cellular metabolism. Central Pathways of Cellular Respiration: In-depth analysis will be conducted on the major stages of cellular respiration, including glycolysis, the link reaction, the citric acid cycle (Krebs cycle), and oxidative phosphorylation. Plant Cellular Respiration: This lecture will conclude with a basic introduction to the unique aspects of plant cellular respiration, highlighting key differences compared to animal respiration. Cellular Respiration Cellular respiration is a metabolic process that converts chemical energy from organic molecules, such as glucose, into adenosine triphosphate (ATP), the primary energy currency of cells. This process involves a series of enzyme-catalysed reactions that break down glucose in the presence of oxygen, releasing carbon dioxide and water as waste products. In eukaryotes this occurs in the: In plants this occurs in the: Cytoplasm Chloroplasts Mitochondria The process is dependent on oxygen availability. This creates two distinct pathways referred to as: Aerobic Respiration Anaerobic Respiration Associated Organelles - Mitochondria Constituents: Membranes Outer Membrane: This smooth membrane surrounds the entire mitochondrion and is permeable to small molecules via porins. Intermembrane Space: The space between the outer and inner membranes. Inner Membrane: Highly folded into cristae with a large surface area, this membrane is impermeable to most molecules. It contains proteins involved in electron transport and ATP synthesis. Mitochondrial Matrix Mitochondrial DNA (mtDNA): A circular DNA molecule that encodes for some mitochondrial proteins. Ribosomes: For protein synthesis within the mitochondrion. Enzymes: Involved in various metabolic processes, including the Krebs cycle and fatty acid oxidation. Associated Organelles - Chloroplasts Constituents: Outer Membrane: A smooth outer boundary. Inner Membrane: Encloses the stroma and thylakoid membranes. Stroma: A fluid-filled space containing enzymes for carbon fixation (Calvin cycle). Thylakoid Membrane: A system of interconnected flattened sacs. Thylakoid Lumen: The space inside the thylakoid sacs. Grana: Stacks of thylakoids. Energy Biomolecules Energy Biomolecules - Adenosine Triphosphate (ATP) ATP can be referred to as the universal energy credit as it is ubiquitous across most species. Phosphate groups have high negative charge, meaning they strongly repel each other via electrostatic repulsion The covalent bonds between the phosphate groups are unstable which requires a low activation energy to break Three phosphate Ribose groups Adenosine Adenosine Triphosphate (ATP)  Energy Biomolecules - Adenosine Triphosphate (ATP) Synthesis Synthesised via a condensation reaction between ADP and Pi The phosphorylation of ADP is catalysed via ATP synthase This process requires energy to be inputted into the molecule (Endergonic) This process utilizes energy derived from the breakdown of glucose in cellular respiration Adenosine Triphosphate Adenosine Diphosphate Adenosine Monophosphate (ATP) (ADP) (AMP)  Energy Biomolecules - Adenosine Triphosphate (ATP) Breakdown Broken down via a hydrolysis reaction This releases instant energy (Exergonic) The available energy decreases with the number of phosphate groups. i.e. ATP has higher energy than ADP Adenosine Triphosphate Adenosine Diphosphate Adenosine Monophosphate (ATP) (ADP) (AMP) Energy Biomolecules - Guanosine Triphosphate (GTP) GTP is an essential molecule with diverse functions in cellular processes. It acts as an energy source, a regulator of protein synthesis, and a key player in signal transduction pathways. While both GTP and ATP are energy-carrying molecules, they have distinct roles: ATP: The primary energy currency of the cell, used in a wide range of cellular processes. GTP: More specialized roles, particularly in protein synthesis, signal transduction, and cytoskeletal dynamics. Three phosphate Ribose groups Guanosine Guanosine Triphosphate (GTP) Energy Biomolecules - Nicotinamide Adenine Dinucleotide (NADH) NADH is a crucial molecule found in all living cells, acting as an essential electron carrier in various metabolic processes, particularly in the production of energy within cells. NADH can produce up to three ATP molecules. Key Roles of NADH: Cellular Respiration: NADH plays a pivotal role in cellular respiration, the process by which cells convert nutrients into energy. During the breakdown of glucose (glycolysis) and the citric acid cycle (Krebs cycle), NAD+ accepts electrons and a hydrogen ion, becoming reduced to NADH. Electron Transport Chain: NADH carries these high-energy electrons to the electron transport chain located within the mitochondria. Here, the electrons are transferred through a series of protein complexes, ultimately combining with oxygen to form water. This process releases energy, which is used to generate ATP, the cell's primary energy currency. Energy Biomolecules - Flavin Adenine Dinucleotide (FADH2) FAD (Flavin Adenine Dinucleotide) and its reduced form, FADH2, are essential electron carriers involved in cellular respiration, particularly in the citric acid cycle (Krebs cycle) and the electron transport chain. FADH2 can produce up to two ATP molecules. Key Roles: Electron Carriers: FAD: The oxidized form, accepts two electrons and two hydrogen ions (protons) during the Krebs cycle, becoming reduced to FADH2. FADH2: The reduced form, carries these high-energy electrons to the electron transport Energy chain. Production: FADH2 contributes to the generation of ATP through oxidative phosphorylation in the electron transport chain, although it yields slightly less ATP per molecule compared to NADH. Glucose Glucose - Sources Carbohydrates Diet: Monosaccharide, disaccharides and polysaccharides can be obtained directly from food sources, which can be reduced to simple sugars. Glycogenolysis: The process by which glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting. Gluconeogenesis Proteins: Proteins are broken down into amino acids. Some of these amino acids can be converted into glucose through a process called gluconeogenesis. This process primarily occurs in the liver and kidneys. Glycerol Conversion: Lipids, such as triglycerides, can be broken down into glycerol and fatty acids. Glycerol can be converted into glucose through gluconeogenesis. Fatty Acid Breakdown: Fatty acids are primarily broken down into acetyl-CoA, which enters the citric acid cycle to produce energy. However, under certain conditions, some acetyl-CoA can be used to synthesize glucose. Glucose - Transport Glucose cannot diffuse directly into cells but enters in either: Na+ independent facilitated diffusion transport system Consists of a family of 14 glucose transporters in cell membranes GLUT-1 to GLUT-14. Tissue specificity for Glut gene expression (Glut 4 in adipose tissues and skeletal muscles, Glut1 in erythrocytes and brain). Glucose movement follows a concentration gradient, that is, from a high GLUT-4 glucose concentration to a lower one. It's important to note that different types of cells express different GLUT proteins, allowing for specific regulation of glucose uptake in various tissues. For example, insulin stimulates the translocation of GLUT4 transporters to the cell surface in muscle and adipose tissue, increasing glucose uptake in response to increased blood glucose levels. Glucose - Transport Glucose cannot diffuse directly into cells but enters in either: Na+ -monosaccharide cotransport system This is an energy-requiring process that transports glucose “against” a concentration gradient. This system is a carrier-mediated process (the movement of glucose is coupled to the concentration gradient of Na+, which is transported into the cell at the same time). The carrier is a sodium-dependent–glucose transporter or SGLT. This type of transport occurs in the epithelial cells of the intestine, renal tubules, Glucose - Astrocyte Neuron Lactate Shuttle Just for information. You do not need to learn this Glycolysis Glycolysis Definition: It is defined as a sequence of reactions transforming glucose to lactate & pyruvate with the production of ATP. 1 molecule of glucose will form 2 molecules of pyruvate Site: Cytosolic fraction of cell End result is twofold: Firstly, to produce energy Secondly, to produce intermediates for other biosynthetic pathways * Take note if the reaction is reversable, what enzyme is catalysing the reaction and Glycolysis – Step 1 Enzyme: Hexokinase Reaction: Glucose + ATP → Glucose 6-phosphate + ADP + H+ Reaction Type: Irreversible Energy Molecules: Use 1 ATP molecule Glycolysis – Step 2 Enzyme: Phosphoglucose Isomerase Reaction: Glucose 6-phosphate ↔ Fructose 6-phosphate Reaction Type: Reversible Energy Molecules: No exchange Note: This reaction involves the conversion of an aldose to a ketose Glycolysis – Step 3 Enzyme: Phosphofructokinase Reaction: Fructose 6-phosphate + ATP → Fructose 1,6-bisphosphate +ADP + H+ Reaction Type: Irreversible Energy Molecules: Use 1 ATP molecule Glycolysis – Step 4 Enzyme: Aldolase Reaction: Fructose 1,6-bisphosphate ↔ Dihydroxyacetone phosphate + Glyceraldehyde 3- phosphate Reaction Type: Reversible Energy Molecules: No exchange Note: This reaction converts a six-carbon molecule into 2 three-carbon molecules Glycolysis – Step 5 Enzyme: Triose phosphate isomerase Reaction: Dihydroxyacetone phosphate ↔ Glyceraldehyde 3- phosphate Reaction Type: Reversible Energy Molecules: No exchange Note: Of the two products from step 4, only glyceraldehyde 3-phosphate (G3P) is used for the remainder of glycolysis but dihydroxyacetone can be converted back to G3P Glycolysis – Step 6 Enzyme: Glyceraldehyde 3-phosphate dehydrogenase Reaction: Glyceraldehyde 3-phosphate + NAD+ + Pi ↔ 1,3- biphosphoglycerate + NADH + H+ Reaction Type: Reversible Energy Molecules: Gain 1 NADH molecule Note: While this reaction generates 1 NADH molecule, it is important to note that this reaction can happen twice due to their being 2 three-carbon molecules of G3P. Glycolysis – Step 7 Enzyme: Phosphoglycerate kinase Reaction: 1,3- biphosphoglycerate + ADP ↔ 3-phosphoglycerate + ATP Reaction Type: Reversible Energy Molecules: Gain 1 ATP molecule Note: While this reaction generates 1 ATP molecule, it is important to note that this reaction can happen twice due to step 4/5. Glycolysis – Step 8 Enzyme: Phosphoglycerate mutase Reaction: 3-phosphoglycerate ↔ 2-phosphoglycerate Reaction Type: Reversible Energy Molecules: No exchange Glycolysis – Step 9 Enzyme: Enolase Reaction: 2-phosphoglycerate ↔ phosphoenolpyruvate + H2O Reaction Type: Reversible Energy Molecules: No exchange Glycolysis – Step 10 Enzyme: Pyruvate kinase Reaction: phosphoenolpyruvate + ADP + H+ → pyruvate + ATP Reaction Type: Irreversible Energy Molecules: Gain 1 ATP molecule Note: While this reaction generates 1 ATP molecule, it is important to note that this reaction can happen twice due to step 4/5. Glycolysis – Summary Glycolysis results in the net products from one six-carbon glucose molecule: Two molecules of ATP Two molecules of NADH (each NADH when oxidized results in 3 ATP) Two molecules of three-carbon pyruvate Link Reaction Link Reaction In the absence of oxygen pyruvate follows the anaerobic pathway to be converted into lactate In aerobic conditions pyruvate moves from the cytosol into the intermembrane space via the voltage- dependent anion channel (VDAC) Pyruvate moves from the intermembrane space into the mitochondrial matrix via the mitochondrial Link Reaction – Aerobic Pathway First step in aerobic respiration Reaction is catalysed via Pyruvate Dehydrogenase Due to two molecules of pyruvate produced in glycolysis, the net yield is: 2 x Acetyl CoA 2 NADH 2 CO2 Link Reaction – Anaerobic Pathway First step in anaerobic respiration Reaction is catalysed via Lactate Dehydrogenase Due to two molecules of pyruvate produced in glycolysis, the net yield is: 2 x Lactate 2 NAD+ Due to the absence of oxygen anaerobic cellular respirate yields only two ATP molecules and results in lactic acid build-up Citric Acid Cycle Citric Acid Cycle Also know as: Krebs cycle Tricarboxylic Acid Cycle (TCA) Szent–Györgyi–Krebs Cycle Numerus routes can enter the citric acid cycle Citric Acid Cycle Occurs in the mitochondrial matrix Acetyl-CoA enters the cycle as a 2- carbon molecule Continuously ongoing if there is a carbon source Multiple checkpoints and feedback mechanisms Note the carbon numbers of each Citric Acid Cycle – Step 1 Enzyme: Citrate synthase Reaction 1: Acetyl CoA + oxaloacetate ↔ S-citryl-CoA Reaction 2: S-citryl-CoA + H2O → citrate + CoASH + H+ Reaction Type: Irreversible Energy Molecules: No exchange Carbon Exchange: (C2) + (C4) → (C6) Citric Acid Cycle – Step 2 Enzyme: Aconitase Reaction 1: Citrate + H2O ↔ cis-aconitate Reaction 2: Cis-aconitate + H2O ↔ isocitrate Reaction Type: Reversible Energy Molecules: No exchange Carbon Exchange: (C6) → (C6) Citric Acid Cycle – Step 3 Enzyme: Isocitrate dehydrogenase Reaction 1: Isocitrate + NAD+ → oxalosuccinate + NADH + H+ Reaction 2: Oxalosuccinate + H+ → α-ketoglutarate + CO2 Reaction Type: Irreversible Energy Molecules: Gain 1 NADH molecule Carbon Exchange: (C6) → (C5) Citric Acid Cycle – Step 4 Enzyme: α-ketoglutarate dehydrogenase Reaction: α-ketoglutarate + CoASH + NAD+ → succinyl-CoA + NADH + H++ CO2 Reaction Type: Irreversible Energy Molecules: Gain 1 NADH molecule Carbon Exchange: (C5) → (C4) Citric Acid Cycle – Step 5 Enzyme: Succinyl-CoA synthase Reaction: Succinyl-CoA + H2O + Pi + GDP → succinate + GTP + CoASH Reaction Type: Irreversible Energy Molecules: Gain 1 GTP molecule Carbon Exchange: (C4) → (C4) Citric Acid Cycle – Step 6 Enzyme: Succinate dehydrogenase Reaction: Succinate + FAD → fumarate + FADH2 Reaction Type: Irreversible Energy Molecules: Gain 1 FADH2 molecule Carbon Exchange: (C4) → (C4) Citric Acid Cycle – Step 7 Enzyme: Fumarase Reaction: Fumarate + H2O → malate Reaction Type: Irreversible Energy Molecules: No exchange Carbon Exchange: (C4) → (C4) Citric Acid Cycle – Step 8 Enzyme: Malate dehydrogenase Reaction: Malate + NAD+ → oxaloacetate + NADH + H+ Reaction Type: Irreversible Energy Molecules: Gain 1 NADH molecule Carbon Exchange: (C4) → (C4) Citric Acid Cycle - Summary 2 carbon atoms enter TCA cycle and leaves as two CO2 Oxaloacetate is not consumed by the cycle. Oxidation of acetyl-CoA in TCA leads to: 3 NADH (each NADH when oxidized results in 3 ATP) 1 FADH2 (each FADH2 when oxidized results in 2 ATP) 1 ATP (GTP) directly from the cycle. So, 12 ATP will be formed for each acetyl Cellular Respiration Net yield so far: Glycolysis 2 NADH 2 ATP Link Reaction 2 NADH 2 CO2 Citric Acid Cycle 6 NADH 2 FADH2 2 ATP (GTP) 4 CO2 Total 10 NADH 2 FADH2 4 ATP 6 CO2 Oxidative Phosphorylation Oxidative Phosphorylation Oxidative phosphorylation is the final stage of cellular respiration. It is a complex series of reactions that occur within the mitochondria of eukaryotic cells. Comprised of the following: Complex I (NADH dehydrogenase) Complex II (Succinate dehydrogenase) Co-Q (quinone) Complex III (Cytochrome b-c1 complex) Cytochrome-c Complex IV (cytochrome c oxidase) Complex V (ATP Synthase) Oxidative Phosphorylation Both NADH and FADH2 are generated in glycolysis and TCA cycle. These reduced coenzymes can enter the electron transport chain where each coenzyme donate a pair of electrons to a specialized set of electron carriers. Each electron carrier is associated with the inner mitochondrial membrane. Oxidative Phosphorylation Oxidative Phosphorylation - Video https://www.youtube.com/watch?v=LQmTKxI4Wn4 Oxidative Phosphorylation There is a high concentration of protons in the intermembrane space compared to the mitochondrial matrix Only complex 1, 3 and 4 move protons into the intermembrane space It is the movement of electrons between redox centres that generates the potential for proton movement NADH and FADH2 are the electron donators Complex 2 facilitates in the movement of electrons via coenzyme Q Complex 4 is the final electron acceptor and generates H2O with the waste products It is the movement of protons from the intermembrane space to the mitochondrial matrix that provides the energy required for ATP synthase to generate ATP from ADP + Pi Total number of ATP produced from the oxidation of glucose Glycolysis (Glucose → Pyruvate) 4 x substrate level phosphorylation 4 ATP 2 NADH 6 ATP Link Reaction (2 Pyruvate → 2 Acetyl-CoA) 2 NADH 6 ATP Citric Acid Cycle (for every 2 X Acetyl CoA) → OXPHOS 6 NADH 18 ATP 2 FADH 4 ATP 2 GTP 2 ATP Total = 40 ATP - 2 ATP = 38 ATP Plant Cellular Respiration Plant Cellular Respiration Plant and mammalian respiration share some fundamental similarities, but they also exhibit key differences: Similarities: Cellular Respiration: Both plants and mammals utilize cellular respiration, a metabolic process that converts chemical energy from organic molecules (primarily glucose) into ATP, the primary energy currency of cells. Glycolysis: The initial stage of breaking down glucose occurs in the cytoplasm of both plant and animal cells, a process known as glycolysis. Krebs Cycle: The Krebs cycle, also known as the citric acid cycle, is a common pathway in both organisms, occurring within the mitochondria. Electron Transport Chain: Both organisms utilize an electron transport chain within the mitochondria to generate ATP through Plant Cellular Respiration Plant and mammalian respiration share some fundamental similarities, but they also exhibit key differences: Differences: Photosynthesis: Plants are unique in their ability to perform photosynthesis, a process that uses sunlight to convert carbon dioxide and water into glucose and oxygen. This allows plants to produce their own food, whereas mammals rely on consuming other organisms for energy. Oxygen Source and Release: Plants: During the day, plants primarily release oxygen through photosynthesis and take in carbon dioxide for respiration. At night, they primarily respire, taking in oxygen and releasing carbon dioxide. Mammals: Continuously take in oxygen from the environment (through lungs or gills) and release carbon dioxide as a waste product of respiration. Respiratory Structures: Plants: Gas exchange occurs through stomata (pores) in leaves, lenticels in stems, and root hairs. Mammals: Possess specialized respiratory organs such as lungs or gills for efficient gas exchange. Energy Sources: Plants: Primarily utilize glucose produced through photosynthesis. Plant Cellular Respiration - Photosynthesis Chloroplasts provide the site for photosynthesis in plants During day light carbon dioxide and water is converted into glucose and oxygen This glucose then enters the glycolic pathway During the night glucose and oxygen is converted back into carbon dioxide and water Summary Mitochondria have a specialized structure that allows them to provide their function Various energy molecules are utilized in the process of cellular respiration During the process of aerobic respiration, a total net of 38 ATP molecules are produced Plants utilized specialized organelles called chloroplast to facilitate photosynthesis Further Reading Chapter 13 p 425 – p452 in Essential Cell Biology, Alberts et al Chapter 14 p 453 – p492 in Essential Cell Biology, Alberts et al