Metabolism, Energy, and Enzymes
Metabolism: The Chemical Reactions of Life
Food as Fuel and Energy Flow
Food Composition: Foods primarily consist of lipids, proteins, and carbohydrates, which are mainly composed of carbon (C), hydrogen (H), and oxygen (O).
Oxidation Reaction: Food molecules are oxidized to release energy, following the general reaction: (C, H, O ext{ food molecules}) + O2 ightarrow CO2 + H_2O + ext{energy}.
Cellular Chemical Work: All organisms must perform chemical work, including:
Energy storage, growth, repair, and replacement of cellular components.
Moving molecules and ions across cell membranes.
Ecosystem Energy Flow: Energy flows through ecosystems as follows:
Light energy from the sun is captured.
Photosynthesis occurs in chloroplasts, converting $CO2 + H2O$ into organic molecules and $O_2$.
Cellular Respiration takes place in mitochondria, breaking down organic molecules in the presence of $O2$ to produce $CO2 + H_2O + ext{ATP}$.
ATP (adenosine triphosphate) powers most cellular work.
Heat energy is released as a byproduct of these transformations.
Laws of Thermodynamics and Metabolism
Metabolism Definition: The totality of an organism's chemical reactions, transforming matter and energy consistent with the laws of thermodynamics.
Metabolism Subtypes:
Catabolism: Pathways that release energy by breaking down complex molecules into simpler compounds.
Example: Proteins, polysaccharides, and fats are broken down into amino acids, monosaccharides, and fatty acids. These further convert to Acetyl CoA, fueling the Citric Acid Cycle and Oxidative Phosphorylation, producing NADH and ATP.
Anabolism: Pathways that consume energy to build complex molecules from simpler ones.
Example: The synthesis of protein from amino acids.
Forms of Energy: Energy is the capacity to cause change and exists in various forms, some capable of performing work.
Specific Energy Requirements for Life:
Energy must be released gradually from food.
Stored in readily accessible forms.
Release from storage must be finely controlled, available precisely when and where needed.
Just enough heat must be released to maintain a constant body temperature.
A form of energy other than heat must be available to drive reactions that are not favorable at body temperature.
Reactions in Living Organisms: Follow the same laws and energy requirements as reactions in a chemistry laboratory.
Spontaneous Reactions: Favorable in the forward direction, release free energy, which is available to do work.
Biological Order and Disorder:
Cells create ordered structures from less ordered materials.
Organisms replace ordered forms of matter and energy with less ordered forms.
Energy flows into an ecosystem as light and exits as heat.
First Law of Thermodynamics (Principle of Conservation of Energy):
The energy of the universe is constant.
Energy can be transferred and transformed, but it cannot be created or destroyed.
Second Law of Thermodynamics:
Every energy transfer or transformation increases the entropy (disorder) of the universe.
During every energy transfer or transformation, some energy is unusable and often lost as heat.
Free-Energy Change (oldsymbol{ ext{ extDelta} G}) and Reaction Spontaneity
Determining Spontaneity: To decide if a process is spontaneous, both change in enthalpy ( ext{ extDelta} H) and change in entropy ( ext{ extDelta} S) must be considered.
Favorable conditions: ext{ extDelta} H is negative (exothermic) and ext{ extDelta} S is positive (increased disorder) $
ightarrow$ spontaneous.Unfavorable conditions: Both ext{ extDelta} H positive and ext{ extDelta} S negative $
ightarrow$ nonspontaneous.Mixed conditions: A process can be unfavorable by enthalpy (positive ext{ extDelta} H) yet be favored by entropy (positive ext{ extDelta} S) and still be spontaneous.
**Free-Energy Change ( ext{ extDelta} G) **:
A quantity used to account for both ext{ extDelta} H and ext{ extDelta} S when determining spontaneity.
Units: kcal/mol or kJ/mol.
Formula: ext{ extDelta} G = ext{ extDelta} H - T ext{ extDelta} S where T is the temperature in Kelvins.
The value of ext{ extDelta} G determines spontaneity:
Exergonic Reactions: Spontaneous reactions or processes that release free energy and have a negative ext{ extDelta} G.
Reactants have higher potential energy than products.
Example: 6O2 + C6H{12}O6
ightarrow 6CO2 + 6H2O (combustion of glucose, releases energy).
Endergonic Reactions: Nonspontaneous reactions or processes that absorb free energy from their surroundings and have a positive ext{ extDelta} G.
Products have higher potential energy than reactants.
Example: Glucose + Fructose
ightarrow Sucrose + H_2O (synthesis of sucrose, requires energy).
Activation Energy: The minimum energy needed to start a chemical reaction.
ATP: Adenosine Triphosphate
Energy Currency: ATP powers cellular work by coupling exergonic reactions to endergonic reactions.
Types of Cellular Work Driven by ATP:
Chemical work: Powering synthesis of macromolecules.
Transport work: Moving molecules/ions across membranes against their concentration gradient.
Mechanical work: Such as muscle contraction or flagellar movement.
Energy Coupling: The use of an exergonic process (like ATP hydrolysis) to drive an endergonic one (like synthesis reactions).
ATP Hydrolysis: The removal of a phosphate group (PO_3^{2-}) via hydrolysis.
Reaction: ATP + H2O ightarrow ADP + HOPO3^{2-} + H^+
This is an exergonic reaction, releasing energy: ext{ extDelta} G = -7.3 ext{ kcal/mol}.
The energy released is available for cellular work and chemical synthesis.
ATP Synthesis (from ADP):
Reaction: ADP + HOPO3^{2-} + H^+ ightarrow ATP + H2O
This is an endergonic reaction, requiring energy: ext{ extDelta} G = +7.3 ext{ kcal/mol}.
Biochemical energy gathered from catabolic (exergonic) reactions is "stored" in ATP.
Energy Storage: Energy is primarily stored in the phosphoanhydride bonds of ATP.
ATP-ADP Interconversion: This cycle is fundamental for biochemical energy production, transport, and utilization within the cell.
Metabolic Pathways and Energy Production Stages
Metabolic Pathways: Sequences of chemical reactions that occur in an organism.
Linear pathways: The product of one reaction serves as the starting material for the next.
Cyclic pathways: A series of reactions regenerates one of the initial reactants (e.g., Citric Acid Cycle).
Spiral pathways: The same set of enzymes progressively builds up or breaks down a molecule.
Four Stages of Energy Production (from food):
Digestion: Large food molecules are broken down by digestive enzymes into smaller molecules.
Carbohydrates $
ightarrow$ glucose and other sugars.Proteins $
ightarrow$ amino acids.Triacylglycerols (fats and oils) $
ightarrow$ glycerol and fatty acids.These smaller molecules are then transferred to the blood for transport throughout the body.
Acetyl-Coenzyme A Production: Small molecules (from digestion) are further broken down into two-carbon acetyl groups, which attach to Coenzyme A.
Structure of Acetyl-CoA: CH_3-C(=O)-S-[Coenzyme ext{ }A]
Acetyl-CoA is a crucial intermediate in the breakdown of all classes of food molecules.
This stage also produces limited ATP and NADH.
Citric Acid Cycle (Krebs Cycle):
Occurs in the mitochondria.
Acetyl-group carbon atoms are oxidized to CO_2.
Energy is captured in the chemical bonds of reduced coenzymes: NADH and $FADH_2$.
Some energy is also stored directly in ATP.
ATP Production (Electron-Transport Chain and Oxidative Phosphorylation):
Occurs in the mitochondria.
Electrons from the reduced coenzymes (NADH and $FADH_2$) are passed down the electron-transport chain.
This process directly produces the majority of the cell's ATP.
Finally, electrons combine with hydrogen ions (H^+) from reduced coenzymes and oxygen (O2) to form H2O.
Enzymes: Biological Catalysts
Definition: Enzymes are primarily protein catalysts (though some non-protein enzymes, like ribozymes, exist) that significantly speed up biochemical reactions by lowering the required activation energy.
Mechanism: Enzymes bind with reactant molecules, called substrates, at their active site, facilitating bond-breaking and bond-forming processes.
Specificity: Enzymes are highly specific, typically catalyzing only a single reaction or a small set of very similar reactions.
This specificity is determined by the complementary 3D shape of the enzyme and its substrates.
Active Site: The specific region on the enzyme where substrate molecules interact.
Binding sites: Responsible for binding and orienting the substrate(s).
Catalytic site: Reduces the chemical activation energy of the reaction.
Induced Fit Model: A mild, dynamic shift in the enzyme's shape occurs at the active site upon substrate binding, optimizing the catalytic efficiency. This is an expansion of the earlier "lock-and-key" model, which proposed rigid complementarity.
Protein Structure and Enzyme Function:
The 3D shape of an enzyme (a protein) is critically determined by its amino acid sequence.
The amino acids within the active site are particularly vital for specific substrate binding and catalytic function.
Cellular Environment: Can significantly impact enzyme function:
Suboptimal temperatures: Can cause the enzyme to denature (lose its specific 3D shape), leading to loss of function.
Suboptimal pHs: Can reduce substrate-enzyme binding and catalytic activity.
How Enzymes Lower Activation Energy: Enzymes facilitate reactions by helping substrates reach their transition state through several mechanisms:
Positioning: Orienting two substrates perfectly for reaction.
Optimal Environment: Providing a favorable chemical environment (e.g., acidic or polar) within the active site.
Stress/Contortion: Applying stress to the substrate, making it less stable and more likely to react.
Temporary Reaction: Temporarily reacting with the substrate, chemically changing it into a less stable, more reactive intermediate.
After a catalyzed reaction, the product(s) are released, and the enzyme reverts to its original state, ready for another catalytic cycle.
Enzyme Regulation
Importance: Regulating enzyme activity allows cells to precisely control their environment and meet specific metabolic needs (e.g., digestive cells working harder after a meal).
Regulation Mechanisms:
Modifications to environmental factors (temperature, pH).
Production of molecules that inhibit or promote enzyme function.
Availability of coenzymes or cofactors.
Enzyme Inhibition:
Competitive Inhibitors: Molecules that have a similar shape to the substrate and compete with the substrate for binding to the active site.
They slow reaction rates but do not affect the maximal reaction rate (if substrate concentration is sufficiently high).
Noncompetitive Inhibitors: Molecules that bind to the enzyme at a location distinct from the active site (allosteric site).
This binding causes a conformational change in the enzyme, resulting in a slower reaction rate and a reduced maximal rate.
Maximal Reaction Rate: The speed of a reaction when substrate concentration is not limiting.
Allosteric Regulation (a specific type of noncompetitive regulation):
Allosteric Inhibitors: Bind to an allosteric site on the enzyme, modifying the active site's shape so that substrate binding is reduced or prevented.
Allosteric Activators: Bind to an allosteric site, modifying the active site's shape to increase its affinity for the substrate, thereby enhancing catalysis.
Drug Discovery Connection: Pharmaceutical drugs are often developed by identifying and synthesizing inhibitors specific to enzymes involved in disease-related metabolic pathways.
Enzyme Cofactors and Coenzymes:
Some enzymes require one or more non-protein molecules, called cofactors or coenzymes, to function.
Cofactors: Inorganic ions, such as Fe^{++}, Mg^{++}, or Zn^{++}.
Example: DNA polymerase requires Zn^{++}.
Coenzymes: Organic molecules, including ATP, NADH, and essential vitamins.
These molecules are primarily obtained through diet.
Feedback Inhibition in Metabolic Pathways:
A critical regulatory mechanism where the end product of a metabolic pathway inhibits an upstream step in the same pathway.
Example: ATP acts as an allosteric inhibitor for some enzymes involved in cellular respiration, preventing overproduction when energy levels are high.