Metabolism and Thermodynamics

Metabolism

• Metabolism is the totality of the chemical reactions in an organism.
• A metabolic pathway begins with a specific molecule and ends with a product.
• Each step in a metabolic pathway is catalyzed by a specific enzyme.

Anabolic vs Catabolic Reactions

• Anabolic reactions involve the construction of complex molecules from simpler ones, requiring energy, such as the synthesis of proteins from amino acids.
• Catabolic reactions involve the breakdown of complex molecules into simpler ones, releasing energy, such as the breakdown of starch into glucose molecules.

Laws of Thermodynamics

• The first law of thermodynamics states that energy is neither created nor destroyed, it is only converted from one form to another.
• The total energy before and after conversion remains the same.
• The second law of thermodynamics states that when energy is converted from one form to another, some energy becomes unavailable to do work.
• Entropy (S) measures the disorder in a system and energy is needed to impose order on the system.

Biological Systems and Energy

• Enthalpy (H) refers to the total energy in biological systems.
• Free energy (G) is the usable energy available for work.
• Unusable energy is represented by entropy (S) multiplied by the absolute temperature (T): H = G + TS.

Changes in Energy and Free Energy

• Changes in energy can be measured in calories or joules.
• Change in free energy (ΔG) of a chemical reaction can be calculated as: ΔG = ΔH - TΔS.
• If ΔG is negative, free energy is released.
• If ΔG is positive, free energy is required.
• If free energy is not available, the reaction won't occur.
• Exergonic reactions release free energy (-ΔG), breaking down ordered reactants into smaller, randomly distributed products and generating disorder.
• Endergonic reactions consume free energy (+ΔG), creating a single, highly ordered product from smaller, less ordered reactants, increasing complexity (order).

ATP and Reactions

• Exergonic reactions include cell respiration and catabolism, they release energy.
• Endergonic reactions include active transport, cell movements, and anabolism, and require energy.
• The synthesis of ATP from ADP and Pi requires energy.
• The hydrolysis of ATP to ADP and Pi releases energy.

Enzymes and Catalysts

• Catalysts increase the rates of chemical reactions, and they are not altered by the reactions themselves.
• Most biological catalysts are enzymes, which are proteins acting as a framework for reactions.
• Reactions are slow due to an energy barrier.
• Activation energy (Ea) is the amount of energy required to start a reaction.
• Activation energy puts the reactants in a reactive mode called the transition state.
• Enzymes lower the energy barrier for a reaction, but do not alter the free energy change (ΔG) of the reaction.
• An uncatalyzed reaction has greater activation energy than a catalyzed reaction.
• Some RNA molecules act as biological catalysts (ribozymes).
• An RNA molecule catalyzes formation of peptide bonds between amino acids.

Enzyme Inhibition

• Irreversible inhibition: an inhibitor covalently bonds to the active site, permanently inactivating the enzyme.
• Aspirin binds to cyclooxygenase (COX), transferring an acetyl group that binds to the active site, which blocks prostaglandin production, thus blocking stimulation of inflammation and pain.
• Reversible inhibition: an inhibitor bonds noncovalently to the active site, preventing substrate binding.
• Competitive inhibitors compete with the natural substrate for binding sites, the degree of inhibition depends on substrate and inhibitor concentrations.
• Uncompetitive inhibitors bind to the enzyme-substrate complex, preventing product release.
• Noncompetitive inhibitors bind to the enzyme at a different site, which changes the active site (allostery).
• Allosteric regulation involves a non-substrate molecule binding to an enzyme at a site different from the active site, and this changes the enzyme shape.
• The active form has the proper shape to bind substrate.
• The inactive form won't bind substrate.
• A non-substrate molecule can be an inhibitor or activator.
• Metabolic pathways: The first reaction is the commitment step, with other reactions following in sequence.
• Feedback inhibition: the final product acts as a noncompetitive inhibitor of the first enzyme, shutting down the pathway.
• Enzymes can be activated when protein kinase adds a phosphate group, and can be deactivated by protein phosphatase.

Aerobic vs Anaerobic Processes

• Aerobic processes/Cellular respiration involves complete oxidation.
• Cellular respiration waste products include water and carbon dioxide.
• Cellular respiration net captured energy per glucose is 32 ATP.
• Anaerobic proceses/Fermentation involves incomplete oxidation.
• Fermentation waste products include lactic acid or ethanol and carbon dioxide.
• Fermentation net captured energy per glucose is 2 ATP.

Oxidation and Reduction

• Oxidation is the chemical process that occurs when an electron is lost.
• Reduction is the chemical process that occurs when an electron is gained.
• Not all redox reactions involve a complete transfer of electrons.
• Electrons aren't lost or gained, but an atom's share of electrons is changed due to polar bonds.
• The carbon-carbon bonds in glucose are shared equally, while the carbon-oxygen bonds in carbon dioxide are polar.
• Oxidation of glucose in aerobic organisms provides about 36 ATP molecules per glucose: C6H12O6 + 6O2 -> 6CO2 + 6H2O + Energy (36-38 ATPs).
• Transfer of electrons is often associated with transfer of hydrogen ions: H = H+ + e–.

Coenzymes

• The coenzyme NAD+ is a key electron carrier in redox reactions.
• Reduction: NAD+ + H+ + 2e- -> NADH
• Oxidation: NADH + H+ + 1/2 O2 -> NAD+ + H2O, exergonic, ΔG = - 52.4 kcal/mol

Glycolysis

• Glycolysis occurs whether oxygen (O2) is present or absent.
• The process occurs in the cytoplasm.
• Net yield of 2 ATP/glucose, as well as 2 pyruvate and 2 NADH.
• All life on earth performs glycolysis.
• Final products are 2 pyruvate, 2 ATP, and 2 NADH.

Pyruvate Oxidation

• Pyruvate Oxidation happens in the mitochondrial matrix.
• Pyruvate is oxidized to acetate and carbon dioxide.
• Acetate binds to coenzyme A to form acetyl CoA.
• It is an exergonic process where one NAD+ is reduced to NADH.

Citric Acid Cycle

• The citric acid cycle starts with Acetyl CoA.
• The cycle's eight reactions completely oxidize the acetyl group to 2 molecules of carbon dioxide.
• The reactants of the citric acid cycle must be replenished for the cycle to continue.
• Energy released is captured by GDP, NAD+, and FAD.
• Oxaloacetate is regenerated in the last step.
• The electron carriers need reoxidization.
• If oxygen is present, it accepts the electrons and forms water.

Products of Glucose Oxidation

• The oxidation of one molecule of glucose yields six molecules of carbon dioxide, 10 molecules of NADH, two molecules of FADH₂, and four molecules of ATP.
• GTP can transfer its high-energy phosphate to form ATP.

Electron Transport Chain

• ATP is synthesized by reoxidation of electron carriers in the presence of oxygen in oxidative phosphorylation.
• The two steps of oxidative phosphorylation are electron transport and chemiosmosis.
• A single reaction in the electron transport chain releases too much free energy at once.
• The electron transport chain has multiple steps where a small amount of energy is released in a series of reactions and captured by an endergonic reaction.
• Protons (H+) are actively transported into the intermembrane space during electron transport.
• The transport creates a concentration gradient and charge difference which makes the potential energy called the proton-motive force.
• Diffusion of protons back across the membrane is coupled to ATP synthesis (chemiosmosis).
• The 2 components of oxidative phosphorylation are: Electron transport & chemiosmosis.

Alternate Acceptors

• Many bacteria and archaea use alternate electron acceptors such as SO₄-², Fe³+, and CO2 in anaerobic respiration.
• Anaerobic respiration can exist where oxygen is scarce or absent.

Fermentation

• Without oxygen, ATP can be made by glycolysis and fermentation.
• This process occurs in the cytoplasm.
• Glucose is only partially oxidized in fermentation.
• Is substrate-level phosphorylation and generates 2 ATP per glucose.
• NAD+ is regenerated to keep glycolysis going.

Photosynthesis

• Sunlight + 6CO₂ + 6H₂O → C₆H₁₂O₆ + 6O₂.
• Carbon source
  • Heterotrophs are organisms that obtain carbon from other organisms.
  • Autotrophs, such as plants, use CO₂ as a carbon source.
• Energy source:
  • Chemotrophs gain energy from chemical compounds.
  • Phototrophs gain energy through photosynthesis.
• Water is the source of oxygen released during photosynthesis; 6 CO₂ + 12 H₂O → C₆H₁₂O₆ + 6 O₂ + 6 H₂O.
• Oxygen atoms in water are in a reduced state but when oxidized they become O₂.
• Carbon atoms in carbon dioxide are in the oxidized state, and when reduced, they become a carbohydrate.
• The light reaction converts light energy to chemical energy as ATP and NADPH.
• The carbon-fixation reaction utilizes ATP and NADPH plus carbon dioxide to produce carbohydrates.
• The absorption spectrum is a plot of wavelengths absorbed by a pigment.
• The action spectrum is a plot of photosynthetic rate against wavelengths of light.

Chlorophyll

• Chlorophyll molecules absorb blue and red light, reflecting or transmitting green light, which is why plants appear green.
• Light energy is captured in light-harvesting complexes and transferred to reaction centers.
• Accessory pigments absorb light in other wavelengths, expanding the range of light usable for photosynthesis.

Photosystems

• Photosystem II’s Chl in the reaction center absorbs light maximally at 680 nm and water gets oxidized.
• Hydrogen ions from water and electron transport capture energy for the chemiosmotic synthesis of ATP.
• Photosystem I absorbs light maximally at 700 nm in the reaction center.
• Photosystem I reduces ferredoxin (Fd), which reduces NADP+ to NADPH.
• RuBP binds to 5-C carbon dioxide, facilitated with ribulose bisphosphate carboxylase/ oxygenase (rubisco) and then immediately becomes two molecules of 3PG.

Calvin Cycle

• The Calvin cycle fixes carbon dioxide to 3PG, reduces 3PG to G3P, and regenerates RuBP.
• In every turn of the cycle, one carbon dioxide is fixed and one RuBP is regenerated.

Carbon-Fixation

• The Calvin cycle is also known as the CO₂ fixation pathway.
• In this cycle, carbon dioxide binds to 5-C RuBP and is catalyzed by rubisco (ribulose bisphosphate carboxylase/oxygenase).
• The 6-C compound product immediately breaks down into two molecules of 3PG.

Photosynthetic Adaptations

• C₃ plants have 3PG (3 carbons) as the first product of CO₂ fixation, but photorespiration occurs on hot days.
• C₄ plants have oxaloacetate (4 carbons) as the first product of CO₂ fixation, and don't typically undergo photorespiration on hot days.