🦠Cell Biology Unit 8 – Cellular Energy and Metabolism

Key Concepts and Terminology

• Metabolism encompasses all chemical reactions involved in maintaining the living state of cells and organisms
• Anabolism constructs molecules from smaller units (requires energy input)
• Catabolism breaks down molecules into smaller units (releases energy)
• Bioenergetics studies energy flow through living systems
• Thermodynamics principles govern energy transformations in biological systems
  • First law of thermodynamics states that energy cannot be created or destroyed, only converted from one form to another
  • Second law of thermodynamics states that every energy transfer increases the entropy (disorder) of the universe
• Endergonic reactions require an input of energy to proceed and are non-spontaneous
• Exergonic reactions release energy and occur spontaneously

Cellular Energy Basics

• Cells require a constant supply of energy to perform vital functions (synthesis of complex molecules, transport of ions and molecules, movement, and cell division)
• Adenosine triphosphate (ATP) serves as the primary energy currency in cells
  • Composed of adenosine (adenine base and ribose sugar) and three phosphate groups
  • Hydrolysis of ATP to ADP (adenosine diphosphate) and inorganic phosphate releases energy for cellular processes
• Cells generate ATP through substrate-level phosphorylation and oxidative phosphorylation
• Cellular respiration is the process of breaking down organic molecules to release energy and synthesize ATP
  • Occurs in three main stages: glycolysis, citric acid cycle, and electron transport chain
• Photosynthesis captures light energy to synthesize organic compounds and generate ATP in photosynthetic organisms (plants, algae, and some bacteria)

ATP and Energy Currency

• ATP is the universal energy currency in living systems
• Structure of ATP consists of adenosine (adenine base and ribose sugar) and three phosphate groups
• High-energy phosphate bonds between the phosphate groups store energy
• Hydrolysis of ATP to ADP and inorganic phosphate (Pi) releases energy for cellular processes
  • $ATP + H_2O \rightarrow ADP + P_i + Energy$
• ATP is continuously recycled in cells through the ATP-ADP cycle
  • ADP is phosphorylated back to ATP using energy from catabolic reactions
• ATP powers various cellular processes (active transport, muscle contraction, nerve impulse transmission, and biosynthesis)
• ATP concentration is tightly regulated to maintain cellular homeostasis

Glycolysis: Breaking Down Glucose

• Glycolysis is the first stage of cellular respiration and occurs in the cytosol
• Glucose (6-carbon sugar) is broken down into two molecules of pyruvate (3-carbon compound)
• Glycolysis consists of ten enzyme-catalyzed reactions divided into two phases
  • Preparatory phase (first five reactions) consumes 2 ATP to convert glucose to fructose-1,6-bisphosphate
  • Payoff phase (last five reactions) yields 4 ATP and 2 NADH (reduced nicotinamide adenine dinucleotide)
• Net yield of glycolysis is 2 ATP and 2 NADH per glucose molecule
• Pyruvate is further oxidized in the citric acid cycle (aerobic conditions) or converted to lactate (anaerobic conditions)
• Glycolysis is a central metabolic pathway in all living organisms
  • Ancient pathway believed to have evolved early in the history of life
• Regulation of glycolysis occurs through allosteric control of key enzymes (hexokinase, phosphofructokinase, and pyruvate kinase)

The Citric Acid Cycle

• The citric acid cycle (also known as the Krebs cycle or tricarboxylic acid cycle) is the second stage of cellular respiration
• Occurs in the mitochondrial matrix following glycolysis
• Pyruvate from glycolysis is oxidized to acetyl-CoA before entering the cycle
• The cycle consists of eight enzyme-catalyzed reactions that oxidize acetyl-CoA to carbon dioxide
• Key steps in the citric acid cycle include:
  • Condensation of acetyl-CoA with oxaloacetate to form citrate
  • Oxidation of isocitrate and α-ketoglutarate, releasing CO2 and generating NADH
  • Substrate-level phosphorylation of GDP to GTP (later converted to ATP)
  • Regeneration of oxaloacetate to continue the cycle
• Each turn of the cycle yields 3 NADH, 1 FADH2 (flavin adenine dinucleotide), and 1 GTP (guanosine triphosphate)
• NADH and FADH2 are electron carriers that transfer electrons to the electron transport chain for ATP synthesis

Electron Transport Chain and Oxidative Phosphorylation

• The electron transport chain (ETC) is the final stage of cellular respiration
• Occurs in the inner mitochondrial membrane and consists of a series of protein complexes (I, II, III, and IV) and electron carriers
• NADH and FADH2 from the citric acid cycle donate electrons to the ETC
  • NADH donates electrons to Complex I, while FADH2 donates electrons to Complex II
• Electrons are transferred through the complexes, releasing energy used to pump protons (H+) from the mitochondrial matrix into the intermembrane space
  • Creates an electrochemical gradient (proton motive force) across the inner mitochondrial membrane
• ATP synthase (Complex V) uses the proton gradient to drive the synthesis of ATP from ADP and Pi
  • Protons flow back into the matrix through ATP synthase, releasing energy for ATP synthesis
• Oxygen serves as the final electron acceptor, combining with protons to form water
• Oxidative phosphorylation couples the electron transport chain to ATP synthesis
• The total ATP yield from the complete oxidation of one glucose molecule is approximately 30-32 ATP

Alternative Metabolic Pathways

• Cells can utilize alternative metabolic pathways depending on the availability of substrates and energy demands
• Fermentation is an anaerobic process that allows glycolysis to continue in the absence of oxygen
  • Pyruvate is converted to lactate (lactic acid fermentation) or ethanol (alcoholic fermentation)
  • Regenerates NAD+ for glycolysis but yields only 2 ATP per glucose
• Beta-oxidation is the breakdown of fatty acids to generate acetyl-CoA for the citric acid cycle
  • Occurs in the mitochondrial matrix and yields NADH and FADH2 for ATP production
• Amino acid catabolism involves the degradation of amino acids for energy production or biosynthesis
  • Amino acids can be converted to pyruvate, acetyl-CoA, or intermediates of the citric acid cycle
• Pentose phosphate pathway is an alternative route for glucose oxidation that generates NADPH and ribose-5-phosphate
  • NADPH is used in biosynthetic reactions and maintains cellular redox balance
  • Ribose-5-phosphate is a precursor for nucleotide synthesis

Regulation of Cellular Metabolism

• Cellular metabolism is tightly regulated to maintain energy homeostasis and respond to changing environmental conditions
• Allosteric regulation involves the binding of effectors (activators or inhibitors) to enzymes at sites other than the active site
  • Modulates enzyme activity in response to cellular metabolite levels
• Covalent modification of enzymes through phosphorylation or dephosphorylation can alter their activity
  • Protein kinases add phosphate groups, while phosphatases remove them
• Transcriptional control regulates the expression of metabolic enzymes at the gene level
  • Transcription factors respond to cellular signals and modulate gene expression
• Hormonal regulation integrates metabolic processes at the organismal level
  • Insulin promotes glucose uptake and storage, while glucagon stimulates glucose release from the liver
• Feedback inhibition is a common regulatory mechanism in metabolic pathways
  • The end product of a pathway inhibits the activity of an earlier enzyme in the pathway
• Compartmentalization of metabolic processes in organelles (mitochondria, peroxisomes) allows for spatial and temporal control of metabolism

Real-World Applications and Research

• Understanding cellular metabolism has important applications in medicine, biotechnology, and agriculture
• Metabolic disorders arise from genetic defects in metabolic enzymes or regulatory pathways
  • Examples include phenylketonuria (PKU), galactosemia, and glycogen storage diseases
  • Diagnosis and management of these disorders rely on knowledge of the underlying metabolic pathways
• Cancer cells exhibit altered metabolism, with increased glucose uptake and aerobic glycolysis (Warburg effect)
  • Targeting cancer metabolism is an active area of research for developing new therapies
• Metabolic engineering involves modifying metabolic pathways in microorganisms to produce valuable compounds
  • Examples include the production of biofuels, pharmaceuticals, and specialty chemicals
• Agricultural research aims to improve crop yields and nutrient content by manipulating plant metabolism
  • Genetic engineering and breeding strategies target photosynthesis, nitrogen fixation, and stress tolerance pathways
• Metabolomics is the systematic study of small molecule metabolites in biological systems
  • Provides insights into cellular metabolism, disease biomarkers, and drug responses
• Integration of cellular metabolism with other biological processes (gene expression, signal transduction) is an active area of research in systems biology