Metabolism, Enzymes, and Energy: Comprehensive Study Notes

ATP synthase and mitochondria

  • ATP synthase is a large enzyme located in the cristae of the mitochondrial inner membrane.
  • Its job is to bond ADP with a third phosphate to form ATP, the cell’s usable energy currency.
  • ATP drives energy-demanding processes: enzymatic activities, motor protein function, active transport, and many other cellular functions.

Metabolism: overview and terminology

  • Metabolism = all chemical reactions that occur in the body; a broad, umbrella term.
  • Two broad categories:
    • Anabolism: building up small molecules into larger ones; requires ATP energy (e.g., bond formation to form polymers like DNA and proteins).
    • Catabolism: breaking down larger molecules into smaller units; releases energy that can be captured to form ATP.
  • Reactions are regulated through enzymatic action; metabolism is highly regulated, not random.
  • We will study a small, representative subset of metabolic reactions, focusing on enzymes, cofactors, and coenzymes, and how these govern pathway flux.

DNA, replication, and protein synthesis (context for later chapters)

  • DNA replication and the cell cycle (mitosis; meiosis in germline) ensure genetic information is passed and that cells can grow and differentiate.
  • DNA stores information in a chemical polymer that cells use to build proteins.
  • Understanding DNA function is foundational for topics like how vaccines (e.g., mRNA vaccines) work and why they do not change DNA (addressing common misinformation).
  • DNA mutations can lead to issues; understanding DNA-protein encoding helps explain genetic disorders and the basis for many diseases.

Metabolism: deeper dive

  • Metabolism involves two major classes of reactions:
    • Anabolic reactions require ATP to synthesize bonds between monomers (e.g., forming proteins, nucleic acids, triglycerides).
    • Catabolic reactions release energy by breaking bonds (e.g., digestion of proteins into amino acids).
  • Anabolism often uses ATP generated by catabolism; there is a strong interdependence between these processes.
  • A key anabolic reaction type: dehydration synthesis (also called condensation synthesis).
    • Dehydration synthesis produces water as a byproduct while forming a bond between monomers.
    • Example: two monosaccharides forming a disaccharide (e.g., glucose + fructose → sucrose + H2O).
    • Similarly used to form polymers like proteins and triglycerides.
  • A key catabolic reaction type: hydrolysis (hydrolytic cleavage).
    • Water is used to break a bond, splitting a larger molecule into smaller units.
    • Example: disaccharides → two monosaccharides (e.g., sucrose + H2O → glucose + fructose).
    • Lipids are cleaved by lipases via hydrolysis to yield glycerol and fatty acids; proteins cleaved by proteases to yield amino acids.
  • Water in metabolism: a not-insignificant portion of daily water comes from metabolic reactions.
    • Approximately 10% of daily water needs can be produced metabolically; the rest comes from diet and fluids.
    • For reference, daily water intake is often around 2 L or more depending on individual needs.

Enzymes: the catalysts of metabolism

  • Enzymes are protein-based catalysts that speed up chemical reactions; they are not consumed in the reactions they catalyze and can be used repeatedly.
  • Enzymes are essential for metabolism; without them most biochemical reactions would not proceed at appreciable rates under physiological conditions.
  • Substrate specificity (lock-and-key and induced-fit concepts): each enzyme has an active site shaped to fit a specific substrate; only the correct substrate binds effectively.
  • Enzymes can catalyze forward and reverse reactions depending on substrate availability and conditions.
  • The place where the substrate binds is the active site; some enzymes have an allosteric site in addition to the active site.
  • Regulation of enzyme activity occurs via allosteric regulation and feedback inhibition; downstream products can bind to the allosteric site to modulate activity (negative feedback).
  • Rate-limiting enzyme: often the first enzyme in a pathway that largely determines the flux through the entire pathway; its activity can be turned on or off to regulate the pathway.
  • Conceptual model (analogy): enzymes are like workers who apply energy or stress to bonds to speed up reactions; they don’t get consumed in the process.
  • Concentration and diffusion: reaction rates depend on how often substrates and enzymes encounter each other, which is influenced by their concentrations and Brownian motion; higher substrate/enzyme concentrations increase rates; lower concentrations slow rates.
  • Examples of enzyme-substrate interactions:
    • Sucrase breaks down sucrose into glucose and fructose via hydrolysis in an active site that fits the sucrose molecule.
    • Different disaccharides require different enzymes (e.g., lactase for lactose, maltase for maltose).
  • Enzyme structure and DNA: the shape of enzymes is determined by their amino acid sequence, which is encoded by DNA; mutations that affect protein folding can disrupt enzyme function and lead to disease.
  • Environmental factors affecting enzyme shape and function:
    • Excess heat can denature proteins (e.g., cooking an egg; albumin denatures from translucent to opaque as it loses its folded structure).
    • Electricity can influence protein conformation (relevant to neuronal signaling, membrane proteins).
    • Extreme pH changes disrupt hydrogen bonding and enzyme structure, impairing function.
    • Certain chemicals can bind to enzymes and alter function (e.g., Botox, a botulinum toxin, binds to membrane proteins on motor neurons to prevent neurotransmitter release, thereby inhibiting muscle contraction).
  • Enzyme types and outcomes:
    • Some enzymes catalyze bond formation (anabolic) and others bond breaking (catabolic); many enzymes can catalyze both directions depending on context.
    • Enzymes are often globular proteins with a defined shape suitable for their substrates.
    • Enzymes can form complexes with cofactors and coenzymes that are essential for activity.

Cofactors and coenzymes

  • Cofactor: a nonprotein component required for enzyme function; can be inorganic ion or small organic molecule.
  • Coenzyme: a subset of cofactors; organic molecules derived from vitamins that assist enzyme function.
  • Hemoglobin example (not an enzyme, but a protein):
    • Contains a heme group with an iron atom at the center; iron binds oxygen in the lungs and releases it in tissues.
    • Iron in heme acts as a cofactor enabling oxygen binding; without iron, hemoglobin cannot function effectively.
  • Vitamins as cofactors/coenzymes:
    • Many B vitamins are essential precursors to coenzymes.
    • Niacin (B3) is the precursor to NAD+; Riboflavin (B2) is the precursor to FAD.
    • NAD+/NADH and FAD/FADH2 are key coenzymes in energy production and electron transport.
  • NAD+/NADH and FAD/FADH2 roles:
    • They function as high-energy electron carriers, shuttling electrons from metabolic reactions to the electron transport chain.
    • Analogy: NAD+/NADH and FAD/FADH2 are like delivery trucks that move electrons to where they’re needed to generate ATP.

Energy, forms of energy, and ATP

  • Energy is the capacity to do work or cause a change in a system.
  • Forms of energy include:
    • Light energy
    • Heat energy
    • Electrical energy
    • Mechanical energy
    • Chemical energy (stored in chemical bonds)
  • Chemical energy and bonds:
    • Energy is stored in chemical bonds; breaking bonds releases energy that can be used to do work.
    • Building bonds stores energy for later use.
  • ATP: adenosine triphosphate, the cell’s main energy currency; often likened to gasoline for cells.
  • ATP hydrolysis and energy transfer:
    • The hydrolysis of ATP releases energy that can be used to drive cellular processes.
    • The key high-energy bond is between the second and third phosphate groups (the β-γ bond).
    • Reaction: ext{ATP} + ext{H}2 ext{O} ightarrow ext{ADP} + ext{P}i + ext{Energy}
    • Approximately 50% of the energy released is used for cellular work; about 50% is dissipated as heat, contributing to body temperature maintenance.
  • ATP cycle and cellular respiration:
    • When ATP is used, it becomes ADP and inorganic phosphate (P_i).
    • Cells resynthesize ATP from ADP + P_i using energy from cellular respiration (breaking down glucose, fats, and proteins) to drive ATP synthase.
    • Overall, cellular respiration: ext{C}6 ext{H}{12} ext{O}6 + 6 ext{O}2
      ightarrow 6 ext{CO}2 + 6 ext{H}2 ext{O} + ext{Energy (ATP)}
  • ATP synthase: the enzyme that uses the proton motive force to drive synthesis of ATP from ADP and P_i.
  • ATP metabolism as a cycle (synthesis and consumption maintain energy supply for cellular processes).

Cellular respiration and energy production

  • Cells obtain energy by breaking bonds in carbohydrates, fats, and proteins; energy released is used to synthesize ATP via ATP synthase.
  • ATP synthase uses energy obtained from the breakdown of nutrients to convert ADP and P_i into ATP.
  • Not all energy from nutrient breakdown is captured as ATP; some is released as heat, which helps maintain body temperature.
  • Energy production and consumption are continuous; cells regulate energy flow to match demand.

Metabolic pathways and regulation (flow and control)

  • Metabolic pathways are sequences of enzyme-catalyzed reactions that convert substrates into products.
  • A basic pathway example: A → (enzyme A) product 1 → (enzyme B) product 2 → (enzyme C) product 3 → (enzyme D) final product.
  • Allosteric regulation and feedback inhibition:
    • An allosteric site on an enzyme can bind a regulatory molecule (often a downstream product).
    • Binding at the allosteric site changes enzyme shape, often reducing its affinity for substrate and slowing the pathway (negative feedback).
    • When product levels drop, inhibition is relieved and the pathway can resume, restoring product levels.
  • Role of rate-limiting enzymes:
    • The rate-limiting enzyme often sits early in the pathway and can be turned on or off to control overall flux through the pathway.
    • Product inhibition at the allosteric site can shut down the rate-limiting step when product levels are high; relief of inhibition occurs when product levels fall.
  • Dysregulation and disease:
    • Dysregulation of metabolic pathways can contribute to diseases, including cancer, where metabolic pathways produce proteins that act as signals for cell division (proto-oncogenes and oncogenes).
    • Dysregulation may involve broader pathway misregulation rather than just allosteric site defects.

DNA, transcription, and translation (connection to metabolism and energy)

  • DNA encodes the instructions for making proteins; transcription and translation translate that information into functional proteins, including enzymes.
  • Mutations can alter enzyme shape and function, affecting metabolism and health.
  • Vaccines (e.g., mRNA vaccines) work by delivering genetic information that directs protein production without altering the DNA of the recipient—this is a key mechanistic point to address misinformation.

Case studies and practical examples of enzymatic chemistry

  • Lactase and lactose intolerance:
    • Lactase is the enzyme that breaks down lactose (a disaccharide) into glucose and galactose.
    • Many people lose lactase activity with age, leading to lactose intolerance and gut distress due to bacterial fermentation of lactose.
  • Sucrose breakdown example:
    • Sucrase hydrolyzes sucrose into glucose and fructose.
    • Demonstrates substrate-specific hydrolysis in which the enzyme fits the substrate in its active site and uses a water molecule to cleave the glycosidic bond.
  • Dehydration synthesis in lipids and proteins:
    • Bonds formed by removing water; e.g., joining glycerol to fatty acids to form triglycerides.
    • Ribosome-mediated peptide bond formation in protein synthesis involves dehydration synthesis between amino acids.
  • Water of metabolism:
    • Water produced during dehydration synthesis contributes to body water; about 10% of daily water needs can be supplied by metabolic water.

Special topics: cofactors, coenzymes, and vitamins

  • Cofactors and coenzymes expand enzyme capabilities and influence enzyme activity and specificity.
  • Hemoglobin and heme example:
    • Hemoglobin carries oxygen in the blood because of heme—the iron-containing center that binds oxygen.
    • Iron acts as a cofactor enabling oxygen binding and release.
  • NAD and FAD in energy metabolism:
    • NAD+ (derived from niacin) and FAD (derived from riboflavin) are key coenzymes that shuttle electrons during cellular respiration.
    • NAD+/NADH and FAD/FADH2 are high-energy electron carriers, essential for efficient energy extraction from nutrients.
  • Vitamins as vitamin-derived cofactors:
    • Water-soluble B vitamins function as cofactors or coenzymes in energy production, protein synthesis, and nucleic acid metabolism.
  • Practical dietary note:
    • The body cannot synthesize sufficient vitamins; a diet rich in fruits, vegetables, and fortified foods provides these essential nutrients.

Regulation and health implications

  • Balance of energy input, storage, and expenditure governs metabolic homeostasis.
  • Feedback inhibition and allosteric regulation help prevent wasteful overproduction of intermediates or products.
  • Mutations or dysregulation of metabolic pathways can contribute to diseases, including cancer, due to altered signaling and energy metabolism.
  • Understanding the interplay between metabolism and energy production is essential to explain physiological responses such as shivering in cold environments (heat production via ATP breakdown).

Quick conceptual recap and takeaways

  • Metabolism comprises anabolic (build) and catabolic (break) processes; both require or liberate energy, respectively.
  • Enzymes are substrate-specific protein catalysts that speed up reactions without being consumed; their activity is tightly regulated.
  • Dehydration synthesis creates bonds with water production; hydrolysis breaks bonds with water consumption.
  • ATP is the cell’s energy currency, with a high-energy β-γ phosphate bond; ATP hydrolysis yields usable energy and heat.
  • Cellular respiration converts nutrients into ATP via a sequence of enzyme-driven steps; energy is stored in ATP and used to power cellular functions.
  • Cofactors and coenzymes (often vitamin-derived) extend enzyme function, enabling essential metabolic processes; NAD+/NADH and FAD/FADH2 are central electron carriers.
  • Enzyme regulation via allosteric sites and feedback inhibition ensures metabolic efficiency and homeostasis; dysregulation can contribute to disease.
  • Real-world relevance: understanding how vaccines work (and don’t alter DNA) helps counter misinformation; metabolic regulation underpins health, exercise, aging, and disease.

Notation and key equations (for quick reference)

  • ATP synthesis:
    ext{ADP} + ext{P}_i
    ightarrow ext{ATP}
  • Dehydration synthesis (general):
    ext{Monomer}1 + ext{Monomer}2
    ightarrow ext{Polymer} + ext{H}_2 ext{O}
  • Hydrolisis (general):
    ext{Polymer} + ext{H}2 ext{O} ightarrow ext{Monomer}1 + ext{Monomer}_2
  • Lactose digestion model:
    ext{Lactose}
    ightarrow ext{Glucose} + ext{Galactose} ext{ (via lactase)}
  • Sucrose digestion model:
    ext{Sucrose}
    ightarrow ext{Glucose} + ext{Fructose} ext{ (via sucrase)}
  • Cellular respiration (overall):
    ext{C}6 ext{H}{12} ext{O}6 + 6 ext{O}2
    ightarrow 6 ext{CO}2 + 6 ext{H}2 ext{O} + ext{Energy (ATP)}
  • NAD+/NADH (simplified redox):
    ext{NAD}^+ + 2e^- + ext{H}^+
    ightarrow ext{NADH}
  • FAD/FADH2 (simplified redox):
    ext{FAD} + 2e^- + 2 ext{H}^+
    ightarrow ext{FADH}_2
  • ATP hydrolysis with heat consideration:
    ext{ATP} + ext{H}2 ext{O} ightarrow ext{ADP} + ext{P}i + ext{Energy} ext{ (≈ 50% work, ≈ 50% heat)}
  • High-energy phosphate bond in ATP (γ bond between β and γ phosphates): ext{P}{eta}- ext{P}{ ext{γ}}
  • General energy form categories listed above (conceptual).