🔬General Biology I Unit 7 – Cellular Respiration

Key Concepts and Terminology

• Cellular respiration: process that breaks down glucose and other organic molecules to release energy in the form of ATP
• Aerobic respiration requires oxygen and yields more ATP compared to anaerobic respiration
• Anaerobic respiration occurs in the absence of oxygen and produces less ATP (lactic acid fermentation, alcoholic fermentation)
• ATP (adenosine triphosphate) is the primary energy currency of the cell
  • Consists of adenosine, ribose sugar, and three phosphate groups
  • Hydrolysis of ATP to ADP + Pi releases energy for cellular processes
• NAD+ (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) are electron carriers that transport electrons during redox reactions
• Substrate-level phosphorylation directly transfers a phosphate group from a substrate to ADP to form ATP
• Oxidative phosphorylation involves the electron transport chain and chemiosmosis to generate ATP

Overview of Cellular Respiration

• Cellular respiration is a series of metabolic reactions that convert the chemical energy in glucose and other organic molecules into ATP
• Occurs in three main stages: glycolysis, citric acid cycle (Krebs cycle), and electron transport chain coupled with oxidative phosphorylation
• Glycolysis takes place in the cytoplasm, while the citric acid cycle and electron transport chain occur in the mitochondria
• The overall equation for cellular respiration: $C_6H_{12}O_6 + 6O_2 \rightarrow 6CO_2 + 6H_2O + \text{ATP}$
• Cellular respiration is a highly regulated process that responds to the energy demands of the cell
• The efficiency of cellular respiration is approximately 40%, with the remaining energy released as heat
• Cellular respiration is closely connected to other metabolic pathways, such as photosynthesis and the pentose phosphate pathway

Glycolysis: The First Stage

• Glycolysis is a series of ten enzyme-catalyzed reactions that break down glucose into two molecules of pyruvate
• Occurs in the cytoplasm of the cell and does not require oxygen
• The overall equation for glycolysis: $\text{Glucose} + 2\text{NAD}^+ + 2\text{ADP} + 2\text{Pi} \rightarrow 2\text{Pyruvate} + 2\text{NADH} + 2\text{ATP} + 2\text{H}^+ + 2\text{H}_2\text{O}$
• Glycolysis can be divided into two phases: the preparatory phase and the payoff phase
  • The preparatory phase consumes 2 ATP to convert glucose into fructose-1,6-bisphosphate
  • The payoff phase yields 4 ATP and 2 NADH, resulting in a net gain of 2 ATP and 2 NADH
• Key enzymes in glycolysis include hexokinase, phosphofructokinase, and pyruvate kinase
• Glycolysis is a highly conserved pathway found in nearly all organisms, indicating its ancient evolutionary origin
• The fate of pyruvate depends on the presence or absence of oxygen (aerobic vs. anaerobic conditions)

The Citric Acid Cycle (Krebs Cycle)

• The citric acid cycle, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle, is a series of eight enzyme-catalyzed reactions that oxidize acetyl-CoA to generate ATP, NADH, and FADH2
• Occurs in the matrix of the mitochondria and requires the presence of oxygen
• Acetyl-CoA, the starting molecule for the citric acid cycle, is derived from pyruvate produced during glycolysis
  • Pyruvate is converted to acetyl-CoA by the pyruvate dehydrogenase complex in the mitochondrial matrix
• Key steps in the citric acid cycle include the formation of citrate, isocitrate, α-ketoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate
• The citric acid cycle generates 1 ATP (through substrate-level phosphorylation), 3 NADH, and 1 FADH2 per acetyl-CoA molecule
• NADH and FADH2 produced in the citric acid cycle are used in the electron transport chain to generate additional ATP
• The citric acid cycle is a central metabolic hub that interacts with various other pathways (amino acid metabolism, fatty acid synthesis, and gluconeogenesis)

Electron Transport Chain and Oxidative Phosphorylation

• The electron transport chain (ETC) is a series of protein complexes embedded in the inner mitochondrial membrane that transfer electrons from NADH and FADH2 to oxygen
• The ETC consists of four main protein complexes (I, II, III, and IV) and two mobile electron carriers (ubiquinone and cytochrome c)
  • Complex I (NADH dehydrogenase) accepts electrons from NADH and passes them to ubiquinone
  • Complex II (succinate dehydrogenase) accepts electrons from FADH2 and passes them to ubiquinone
  • Complex III (cytochrome bc1 complex) transfers electrons from ubiquinone to cytochrome c
  • Complex IV (cytochrome c oxidase) transfers electrons from cytochrome c to oxygen, forming water
• As electrons flow through the ETC, protons (H+) are pumped from the mitochondrial matrix into the intermembrane space, creating an electrochemical gradient
• Oxidative phosphorylation harnesses the energy of the proton gradient to generate ATP through the action of ATP synthase (sometimes referred to as Complex V)
  • Protons flow back into the matrix through ATP synthase, driving the synthesis of ATP from ADP and Pi
• The electron transport chain and oxidative phosphorylation are tightly coupled processes that together yield the majority of ATP produced during cellular respiration
• The number of ATP molecules generated per NADH and FADH2 varies depending on the specific electron transport chain entry point (NADH yields ~2.5 ATP, while FADH2 yields ~1.5 ATP)

Energy Yield and Efficiency

• The total ATP yield from the complete oxidation of one glucose molecule through cellular respiration is approximately 30-32 ATP
  • Glycolysis: 2 ATP (net gain)
  • Citric Acid Cycle: 2 ATP (per glucose molecule, as each glucose yields 2 acetyl-CoA)
  • Electron Transport Chain and Oxidative Phosphorylation: ~26-28 ATP (assuming 2.5 ATP per NADH and 1.5 ATP per FADH2)
• The theoretical maximum ATP yield per glucose is 38 ATP, but the actual yield is lower due to factors such as proton leakage and the cost of transporting ATP and NADH between the cytoplasm and mitochondria
• The efficiency of cellular respiration is approximately 40%, meaning that 40% of the energy in glucose is captured as ATP, while the remaining 60% is lost as heat
• The high efficiency of cellular respiration is attributed to the tight coupling of the electron transport chain and oxidative phosphorylation, as well as the highly organized structure of the mitochondria
• Factors that can affect the efficiency of cellular respiration include the availability of oxygen, the presence of uncoupling proteins, and the overall health of the mitochondria

Regulation and Control Mechanisms

• Cellular respiration is a highly regulated process that responds to the energy demands of the cell and the availability of substrates
• Key regulatory enzymes in glycolysis include hexokinase, phosphofructokinase, and pyruvate kinase
  • Hexokinase is inhibited by its product, glucose-6-phosphate, preventing excessive glucose breakdown when energy levels are high
  • Phosphofructokinase is allosterically regulated by ATP (inhibitor) and AMP (activator), ensuring that glycolysis is responsive to the cell's energy state
• The citric acid cycle is regulated by the availability of substrates and the activity of key enzymes such as citrate synthase and isocitrate dehydrogenase
• The electron transport chain and oxidative phosphorylation are regulated by the electrochemical proton gradient and the availability of ADP and Pi
  • A high proton gradient and low ADP levels slow down electron transport and ATP synthesis, while a low proton gradient and high ADP levels stimulate these processes
• Hormones such as insulin, glucagon, and epinephrine can modulate cellular respiration by altering the activity of regulatory enzymes and the availability of substrates
• Dysregulation of cellular respiration is associated with various metabolic disorders (diabetes, obesity) and neurodegenerative diseases (Alzheimer's, Parkinson's)

Connections to Other Metabolic Pathways

• Cellular respiration is closely connected to other metabolic pathways, allowing cells to utilize a variety of energy-rich molecules and adapt to changing environmental conditions
• Glycolysis is linked to the pentose phosphate pathway, which generates NADPH and ribose-5-phosphate for biosynthetic reactions
  • Glucose-6-phosphate, an intermediate in glycolysis, can be diverted to the pentose phosphate pathway when the cell requires more NADPH or ribose-5-phosphate
• The citric acid cycle is a central hub for the metabolism of amino acids and fatty acids
  • Amino acids can be converted into citric acid cycle intermediates (α-ketoglutarate, oxaloacetate) and oxidized for energy production
  • Fatty acids are broken down into acetyl-CoA through β-oxidation and can enter the citric acid cycle for further oxidation
• The electron transport chain and oxidative phosphorylation are linked to the process of photosynthesis in plants and some bacteria
  • Light-dependent reactions of photosynthesis generate NADPH and ATP, which can be used to power the Calvin cycle and other metabolic processes
  • In the absence of light, plants can utilize the products of cellular respiration (ATP and NADH) to maintain essential functions
• Cellular respiration and fermentation are alternative pathways for energy production in the absence of oxygen
  • Under anaerobic conditions, cells can regenerate NAD+ through fermentation pathways (lactic acid fermentation, alcoholic fermentation) to maintain the continuation of glycolysis