Energy, Enzymes, and Metabolism Vocabulary

Energy and Chemical Reactions

• A spontaneous reaction is not necessarily a fast reaction.
• Catalyst: An agent that speeds up the rate of a chemical reaction without being consumed during the reaction.
• Enzymes: Protein catalysts in living cells.
• Ribozymes: RNA molecules with catalytic properties.

Why Catalysts Are Necessary

• Catalysts are needed to speed up reactions because breaking or forming covalent bonds involves stretching or straining bonds to allow proper molecular interaction.
• Enzymes facilitate these interactions.

Activation Energy (EA)

• Activation energy (EA): The energy required to start a reaction by breaking bonds in reactant molecules.
• Transition state: An unstable state where bonds are stretched.
• Common ways to overcome EA:
  • Large amounts of heat
  • Using enzymes to lower activation energy
• Heat is a nonselective catalyst, and high temperatures can denature proteins.

Burning Glucose: An Exergonic Reaction

• The breakdown of glucose to CO2 and H2O is spontaneous but slow without a catalyst.
• It occurs without additional energy input but is not necessarily fast.

Enzymes Lower Activation Energy

• Enzymes catalyze reactions by lowering the EA.
• Enzymes do not affect \Delta G (Gibbs free energy change).
• Enzymes only speed up reactions that would occur without them.

How Enzymes Lower EA

• Positioning reactants together to facilitate bonding.
• Straining bonds in reactants to make it easier to achieve the transition state.
• Changing the local environment.
• Direct participation through very temporary bonding.

Enzyme Specificity

• Enzymes are specific to the reactions they catalyze.
• Substrates: Reactant molecules on which an enzyme acts.
• Active site: The region on the enzyme where the substrate binds.
• Enzyme-substrate complex: Enzyme + substrate.
• Specificity results from the fit between the shape of the active site and the substrate.

Enzyme-Substrate Binding

• High specificity results from the fit between the shape of the active site and the substrate.
• Lock and key metaphor: Only the right key (substrate) fits in the lock (enzyme).

Induced Fit

• Enzymes change shape due to chemical interactions with the substrate.
• This induced fit involves conformational changes and brings chemical groups of the active site together.

Steps of an Enzyme-Catalyzed Reaction

1. Substrates (ATP and glucose) bind to the enzyme (hexokinase).
2. The enzyme undergoes a conformational change that binds the substrates more tightly (induced fit).
3. Substrates are converted to products.
4. Products (ADP and glucose-6-phosphate) are released; the enzyme is ready to be reused.

Enzyme Reactions

• V_{max} = Velocity of reaction near maximum rate.
• Saturation = Plateau where nearly all active sites are occupied by the substrate.
• K_M (Michaelis constant) = Substrate concentration where velocity is half of maximum.

Inhibition

• Competitive Inhibition
  • A molecule binds to the active site.
  • Inhibits the ability of the substrate to bind.
  • Apparent K_M increases – more substrate is needed.
• Noncompetitive Inhibition
  • Lowers V{max} without affecting KM.
  • The inhibitor binds to an allosteric site, not the active site.

Environmental Factors Affecting Enzyme Activity

• Temperature and pH
• Most enzymes function maximally in a narrow range of temperature and pH.

Metabolism

• Metabolism: The sum of all chemical reactions that take place in a cell.
• A metabolic pathway begins with a specific molecule and ends with a product.
• Each step is catalyzed by a specific enzyme.

Overview of Metabolic Pathways

• Chemical reactions occur in metabolic pathways.
• Catabolic pathways:
  • Break down cellular components
  • Exergonic (release energy)
• Anabolic pathways:
  • Synthesize cellular components
  • Endergonic (require energy)
  • Must be coupled to an exergonic reaction

Catabolic and Anabolic Pathways

• Catabolic pathways release energy (exergonic) by breaking down complex molecules into simpler compounds.
• Anabolic pathways (biosynthetic pathways) consume energy (endergonic) to build complex molecules from simpler ones.
• Anabolic pathways must be coupled to exergonic reactions to proceed.

Catabolic Reactions

• Breakdown of reactants.
• Used for recycling building blocks.
• Used for energy to drive endergonic reactions.
• Energy is stored in intermediates such as ATP and NADH.

How to Make ATP

1. Substrate-level phosphorylation:
   • Enzyme directly transfers a phosphate from one molecule to another.
   • Oxygen is not needed.
2. Chemiosmosis (oxidative phosphorylation):
   • Energy stored in an electrochemical gradient is used to make ATP from ADP and Pi (inorganic phosphate).

Redox Reactions

• Redox reactions transfer electrons between reactants.
• Oxidation: Removal of electrons.
• Reduction: Addition of electrons.
• OIL RIG: Oxidation Is Loss, Reduction Is Gain.

Electron Carriers

• Electrons removed by oxidation of organic molecules are used to create energy intermediates like NADH from NAD+ (Nicotinamide adenine dinucleotide).

Nicotinamide Adenine Dinucleotide (NAD+)

• NAD+
  • Oxidized form
• NADH
  • Reduced form
  • Energy intermediate
  • Oxidation of NADH is exergonic and can donate electrons.

Role of NAD+ in Cellular Respiration

• Electrons from organic compounds are usually first transferred to NAD+.
• As an electron acceptor, NAD+ functions as an oxidizing agent during cellular respiration.
• Each NADH represents a lot of stored energy that can be used to synthesize ATP.
• NADH donates electrons during synthesis reactions to energize them.

Anabolic Reactions

• Biosynthetic reactions.
• Makes large macromolecules or smaller molecules not available from food.
• Requires an energy source from a catabolic reaction, e.g., ATP.

Regulation of Metabolic Pathways

• Gene regulation:
  • Turn genes on or off.
• Cellular regulation:
  • Cell-signaling pathways like hormones.
• Biochemical regulation:
  • Feedback inhibition – the product of a pathway inhibits early steps to prevent over-accumulation of the product.

Feedback Inhibition

• Feedback inhibition – the end product of a metabolic pathway shuts down the pathway.
• Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than needed.
• Allosteric regulation:
  • A regulatory molecule binds to a protein at one site and affects the protein’s function at another site.
  • It may either inhibit or stimulate an enzyme’s activity.

Recycling of Organic Molecules

• Most large molecules exist for a relatively short period.
• Half-life: The time it takes for 50% of the molecules to be broken down and recycled.
• All living organisms must efficiently use and recycle organic molecules.

Expression of Genome

• The expression of the genome allows cells to respond to changes in their environment.
• RNA and proteins are made when needed and broken down when they are not.
• mRNA degradation is important to conserve energy by degrading mRNAs for proteins no longer required and to remove faulty copies of mRNA.

Proteasome

• Proteasome: A complex that breaks down proteins using protease enzymes.
• Large proteases cleave bonds between amino acids.
• Ubiquitin tags target proteins to the proteasome to be broken down and recycled.
• Ubiquitin tagging allows the cell to degrade improperly folded proteins and rapidly degrade proteins to respond to changing cell conditions.

Lysosomes and Autophagy

• Lysosomes contain hydrolases to break down proteins, carbohydrates, nucleic acids, and lipids.
• They digest substances taken up by endocytosis.
• Autophagy: Recycling worn-out organelles using an autophagosome. Functionally, it's like a cellular garbage disposal. It's important for maintaining cellular health and can be dysregulated in various diseases. Autophagy is also a response allowing cells to survive nutrient deprivation.