Enzymes and Metabolism

Reversible Reactions

Chemical reactions in biological systems can proceed in both directions, reaching a state of equilibrium where the rate of the forward reaction equals the rate of the reverse reaction.

• Reversible reactions allow cells to regulate metabolic pathways efficiently.

• Enzymes can catalyze both the forward and reverse reactions, depending on substrate and product concentrations.

• Example: The conversion of glucose-6-phosphate to fructose-6-phosphate in glycolysis is reversible.

Catabolic vs. Anabolic Pathways

Metabolism is divided into two main types of pathways: catabolic (breaking down molecules) and anabolic (building molecules).

• Catabolic pathways: Break down complex molecules into simpler ones, releasing energy. Example: Cellular respiration (glucose breakdown).

• Anabolic pathways: Build complex molecules from simpler ones, consuming energy. Example: Protein synthesis from amino acids.

First and Second Laws of Thermodynamics

• First Law: Energy cannot be created or destroyed, only transformed. The total energy in a closed system remains constant.

• Second Law: Every energy transfer increases the entropy (disorder) of the universe. Some energy is lost as heat.

• Entropy (S): A measure of disorder. Negative entropy change (decrease in disorder) occurs during processes like protein folding.

Gibbs Free Energy Change ()

Gibbs free energy determines whether a reaction is spontaneous.

• Equation:

• If , the reaction is spontaneous (exergonic).

• If , the reaction is non-spontaneous (endergonic).

Exergonic vs. Endergonic Reactions

• Exergonic: Release energy; ; spontaneous. Example: Cellular respiration.

• Endergonic: Require energy input; ; non-spontaneous. Example: Photosynthesis.

Activation Energy

• Activation energy (Ea): The initial energy input required to start a reaction.

• Enzymes lower activation energy, increasing reaction rates.

ATP and Energy Coupling

• ATP (adenosine triphosphate): The main energy currency of the cell.

• Energy coupling uses the energy released from ATP hydrolysis to drive endergonic reactions.

Enzymes and Their Function

• Enzyme: A biological catalyst, usually a protein, that speeds up reactions without being consumed.

• Active site: The region on the enzyme where the substrate binds and the reaction occurs.

• Optimum pH and temperature: Each enzyme works best at specific pH and temperature ranges.

Enzyme Inhibition and Regulation

• Competitive inhibitors: Bind to the active site, blocking substrate binding.

• Non-competitive inhibitors: Bind elsewhere, changing enzyme shape and reducing activity.

• Allosteric inhibitors/activators: Bind to sites other than the active site, altering enzyme activity.

• Feedback inhibition: The end product of a pathway inhibits an earlier step, regulating pathway activity.

• Enzyme kinetics – Saturation: At high substrate concentrations, all enzyme active sites are occupied, and the reaction rate plateaus (Vmax).

Cellular Respiration and Energy Production

ATP Structure and Hydrolysis

• ATP: Composed of adenine, ribose, and three phosphate groups.

• ATP hydrolysis: Releases energy due to repulsion between phosphate groups and resonance stabilization of products.

Energy Coupling and Electron Carriers

• NAD+ and NADH: Electron carriers; NADH stores energy by accepting electrons.

• FADH2: Another electron carrier in respiration.

• Redox reactions: Involve transfer of electrons; oxidation is loss, reduction is gain of electrons.

Phosphorylation Mechanisms

• Kinases: Enzymes that add phosphate groups to molecules.

• Substrate-level phosphorylation: Direct transfer of phosphate to ADP to form ATP.

• Oxidative phosphorylation: ATP synthesis powered by the electron transport chain and chemiosmosis.

Types of Respiration

• Obligate aerobes: Require oxygen for survival.

• Obligate anaerobes: Cannot survive in oxygen.

• Facultative anaerobes: Can survive with or without oxygen.

Mitochondrial Structure

• Cristae: Folds of the inner membrane, increase surface area for ATP production.

• Matrix: Central compartment containing enzymes for the citric acid cycle.

• Intermembrane space: Space between inner and outer membranes, important for proton gradient.

Glycolysis

• Location: Cytoplasm.

• Phases: Energy investment (uses 2 ATP), energy harvest (produces 4 ATP, 2 NADH).

• Net effect: Glucose → 2 pyruvate + 2 ATP (net) + 2 NADH.

• Redox: NAD+ is reduced to NADH.

Pyruvate Oxidation

• Location: Mitochondrial matrix.

• Products: 2 acetyl-CoA, 2 CO2, 2 NADH per glucose.

• Pyruvate transport: Pyruvate enters mitochondria via transport proteins.

Citric Acid Cycle (Krebs Cycle)

• Location: Mitochondrial matrix.

• Input: 2 acetyl-CoA per glucose.

• Output: 4 CO2, 6 NADH, 2 FADH2, 2 ATP (per glucose).

• Carbon atoms: 4 carbons (from 2 acetyl-CoA) enter per glucose.

Electron Transport Chain (ETC) and Chemiosmosis

• Location: Inner mitochondrial membrane.

• Electron flow: NADH and FADH2 donate electrons to complexes; electrons move through chain to oxygen (final acceptor).

• Proton gradient: Protons are pumped into the intermembrane space, creating an electrochemical gradient.

• ATP synthase: Protons flow back into the matrix through ATP synthase, driving ATP production.

Fermentation and Anaerobic Respiration

• Fermentation: Anaerobic process; regenerates NAD+ by reducing pyruvate.

• Lactic acid fermentation: Pyruvate is reduced to lactate (e.g., in muscles).

• Ethanol fermentation: Pyruvate is converted to ethanol and CO2 (e.g., in yeast).

• Anaerobic respiration: Uses electron acceptors other than oxygen.

Feedback Inhibition in Respiration

• Key enzymes in glycolysis and the citric acid cycle are regulated by feedback inhibition (e.g., phosphofructokinase is inhibited by ATP).

Photosynthesis

Light and Pigments

• Photon: A particle of light energy.

• Wavelength: Determines energy and color of light; shorter wavelengths have more energy.

• Chlorophyll a and b: Main pigments; absorb light for photosynthesis.

• Accessory pigments: Carotenoids and others broaden the spectrum of absorbed light.

Leaf and Chloroplast Structure

• Stomata: Pores for gas exchange.

• Mesophyll: Photosynthetic tissue.

• Epidermis: Protective outer layer.

• Chloroplast: Contains thylakoids (stacked into grana), stroma (fluid), and lumen (inside thylakoids).

Photosystems and Light Reactions

• Photosystems: Complexes of pigments and proteins; absorb light and transfer energy to reaction centers.

• Primary electron acceptor: Receives excited electrons from chlorophyll.

• Electron transport chain: Transfers electrons, pumps protons, and generates ATP and NADPH.

• NADP+: Final electron acceptor in light reactions; reduced to NADPH.

• Water: Electron donor; split to provide electrons and release O2.

Electron Flow and ATP Synthesis

• Linear electron flow: Produces ATP and NADPH.

• Cyclic electron flow: Produces ATP only; no NADPH or O2 generated.

• Chemiosmosis: Proton gradient drives ATP synthesis via ATP synthase.

Calvin Cycle (C3 Pathway)

• Location: Stroma of chloroplast.

• Phases: Carbon fixation, reduction, regeneration of RuBP.

• Rubisco: Enzyme that fixes CO2 to RuBP.

C4 and CAM Plants

• C4 plants: Use spatial separation to minimize photorespiration (e.g., maize).

• CAM plants: Use temporal separation; open stomata at night (e.g., cacti).

Cell Signaling

Ligands, Receptors, and Signal Types

• Ligand: A signaling molecule that binds to a receptor.

• Receptor: Protein that detects and responds to a ligand.

• Transmembrane receptors: Span the membrane (e.g., G protein-coupled receptors, receptor tyrosine kinases).

• Hormone receptors: Can be intracellular (e.g., steroid hormone receptors).

• Neurotransmitters: Chemical messengers at synapses.

Types of Signaling

• Autocrine: Cell signals itself (e.g., immune cells).

• Paracrine: Signals nearby cells (e.g., neurotransmitters).

• Endocrine: Signals distant cells via bloodstream (e.g., hormones).

Cell Junctions

• Gap junctions: Direct cytoplasmic connections in animal cells.

• Plasmodesmata: Direct cytoplasmic connections in plant cells.

Stages of Cell Signaling

• Reception: Ligand binds to receptor.

• Transduction: Signal is relayed and amplified inside the cell (often via phosphorylation cascades and second messengers).

• Response: Cellular activity changes (e.g., gene expression, enzyme activity).

Receptor Types and Signal Transduction

• Ligand-gated ion channels: Open in response to ligand binding, allowing ion flow.

• Receptor tyrosine kinases: Dimerize and autophosphorylate; activate pathways (e.g., Ras protein).

• G protein-coupled receptors (GPCRs): Activate G proteins, which relay signals to other proteins.

• Kinases: Add phosphate groups; phosphatases: Remove them.

• Phosphorylation cascades: Series of kinases activating each other, amplifying the signal.

• Second messengers: Small molecules (e.g., cAMP, Ca2+, IP3, DAG) that propagate signals.

• cAMP degradation: By phosphodiesterase enzyme.

• Amplification: One ligand can activate many molecules, amplifying the response.

• Transcription factors: Proteins that regulate gene expression as a final response.

Cell Division: Mitosis

Binary Fission

• Binary fission: Prokaryotic cell division; DNA replicates, cell splits into two.

Chromatin and Chromosomes

• Euchromatin: Loosely packed, transcriptionally active DNA.

• Heterochromatin: Densely packed, transcriptionally inactive DNA.

• Chromosome: DNA molecule with associated proteins.

• Sister chromatids: Identical copies of a chromosome, joined at the centromere.

• Homologous pairs: Chromosomes with the same genes, one from each parent.

Ploidy

• Haploid (n): One set of chromosomes.

• Diploid (2n): Two sets of chromosomes.

• Polyploidy: More than two sets of chromosomes.

Cell Cycle and Mitosis

• Interphase: G1 (growth), S (DNA synthesis), G2 (preparation for division), G0 (resting).

• Mitotic phase: Mitosis (nuclear division) and cytokinesis (cytoplasm division).

• Five stages of mitosis:

  1. Prophase: Chromosomes condense, spindle forms.

  2. Prometaphase: Nuclear envelope breaks down, kinetochores attach to spindle.

  3. Metaphase: Chromosomes align at the metaphase plate.

  4. Anaphase: Sister chromatids separate to opposite poles.

  5. Telophase: Nuclear envelopes reform, chromosomes decondense.

• Role of microtubules: Form the mitotic spindle, move chromosomes.

• Spindle and kinetochores: Spindle fibers attach to kinetochores on chromosomes.

• Mitotic spindle: Composed of microtubules and associated proteins.

Cytokinesis

• Animals: Cleavage furrow forms, pinching the cell in two.

• Plants: Cell plate forms, dividing the cell.

Cell Cycle Regulation

• Checkpoints: Control progression (e.g., spindle checkpoint ensures chromosomes are attached before separation).

• Cyclins and cyclin-dependent kinases (CDKs): Regulate cell cycle transitions.