Metabolism, Thermodynamics, and Enzyme Function in Biology

Metabolism

Overview of Metabolism

Metabolism encompasses all chemical reactions occurring within an organism. These reactions are organized into metabolic pathways, each beginning with a specific molecule and ending with a product, with each step catalyzed by a specific enzyme.

• Catabolic pathways release energy by breaking down complex molecules (e.g., cellular respiration breaks down glucose).

• Anabolic pathways consume energy to build complex molecules (e.g., synthesis of proteins from amino acids).

Example: The breakdown of glucose during cellular respiration is a catabolic pathway, while the synthesis of proteins from amino acids is anabolic.

Thermodynamics in Biology

First Law of Thermodynamics

The first law, also known as the law of conservation of energy, states that energy can be transferred and transformed, but it cannot be created or destroyed.

• Energy entering and leaving a system can always be tracked.

Second Law of Thermodynamics

The second law states that the entropy (disorder) of the universe is always increasing. Entropy is a primary driving force for all physical processes.

• The entropy of a closed system is greater than or equal to zero.

• As entropy increases, the disorder of something is also increasing.

• Spontaneous reactions increase the entropy of the universe.

• System + surroundings = universe.

• Human activity and evolution do not violate the second law.

• An individual reaction can have positive or negative entropy (about 50/50 split).

Example: The breakdown of complex molecules into simpler ones increases entropy.

Free Energy

Definition and Importance

Free energy is the energy in a system that can do work. It is the most basic form of energy currency in the cell.

• Positive free energy (ΔG > 0): Unfavorable, nonspontaneous, endergonic; energy input required.

• Negative free energy (ΔG < 0): Favorable, spontaneous, exergonic; energy is released.

• ΔH = enthalpy (heat), ΔS = entropy, T = temperature in Kelvin.

Formula:

$\Delta G = \Delta H - T\Delta S$

Only processes with a negative ΔG are spontaneous or favorable.

ATP in Reactions

Role of ATP

ATP (adenosine triphosphate) is the main energy currency of the cell. It mediates most energy coupling in cells, using exergonic processes to drive endergonic ones.

• ATP often drives endergonic reactions by phosphorylation (transferring a phosphate group to another molecule).

• The recipient molecule is called a phosphorylated intermediate.

• ATP is a renewable resource, regenerated by addition of a phosphate group to ADP.

Example: ATP hydrolysis provides energy for muscle contraction and active transport.

Enzymes

Enzyme Structure and Function

Enzymes are biological catalysts, usually proteins, that speed up chemical reactions without being consumed.

• They lower the activation energy (transition state barrier) of reactions.

• Enzymes do not affect the change in free energy (ΔG); they only speed up reactions that would occur eventually.

• The substrate is the reactant that binds to the enzyme's active site.

• The enzyme-substrate complex forms when the substrate binds to the enzyme.

Active Site and Induced Fit

• The active site is the region where the substrate binds.

• Enzymes orient substrates, strain substrate bonds, provide a favorable microenvironment, and sometimes form covalent bonds with the substrate.

• Induced fit: The enzyme changes shape to better fit the substrate upon binding.

Enzyme Specificity and Environmental Effects

• Altered amino acids in enzymes may change substrate specificity.

• Homologous enzymes in different organisms have slightly different amino acid sequences.

• Environmental conditions (e.g., pH, temperature) can affect enzyme activity and favor different forms.

Cofactors

Role of Cofactors

Cofactors are nonprotein helpers required for enzyme activity. They can be inorganic (metal ions) or organic (coenzymes).

• Many vitamins function as coenzymes.

Enzyme Inhibitors

Types of Inhibitors

• Competitive inhibitors: Bind to the active site and compete with the substrate.

• Noncompetitive inhibitors: Bind away from the active site, decreasing enzyme activity.

• Examples include toxins, poisons, pesticides, antibiotics, and many drugs.

Regulation of Enzyme Activity

Genetic and Biochemical Regulation

• Switching on or off the genes that encode specific enzymes.

• Regulating enzyme activity through allosteric regulation and cooperativity.

• Feedback regulation and enzyme localization.

• Enzymes cannot be active at full speed all the time.

Allosteric Regulation of Enzymes

• Allosteric regulation may inhibit or stimulate enzyme activity.

• A regulatory molecule binds to a site other than the active site, affecting the protein's function at another site.

• Binding can lock the enzyme in its active or inactive form.

• Cooperativity: A specific form of allosteric regulation where binding of one substrate molecule primes the enzyme to bind additional substrates more easily.

Feedback Regulation

• In feedback regulation, the end product of a metabolic pathway inhibits an earlier step, preventing waste of resources.

• Feedback inhibition is a common method of metabolic control.

Localization of Enzymes

• Enzyme localization within the cell is another method of controlling metabolic pathways.

• For example, enzymes for cellular respiration are located in the mitochondria.

Summary Table: Types of Enzyme Inhibition

Type	Binding Site	Effect on Enzyme Activity	Example
Competitive Inhibitor	Active site	Competes with substrate, decreases activity	Penicillin
Noncompetitive Inhibitor	Allosteric site (not active site)	Decreases activity by changing enzyme shape	Heavy metals (e.g., lead)

Additional Notes and Clarifications

• Entropy cannot be measured directly; it is inferred from changes in system disorder.

• Free energy combines enthalpy and entropy to predict reaction spontaneity.

• Spontaneous reactions can occur without energy input; nonspontaneous reactions require energy.

• Substrates and inhibitors often bind with non-covalent bonds.

• High pH means higher concentration of OH- ions.

Additional info: Allosteric regulation is not the same as noncompetitive inhibition, though both involve binding at sites other than the active site. Allosteric regulation can both inhibit and activate enzymes, while noncompetitive inhibition only decreases activity.