Biological Molecules and Proteins

Building Blocks of Life

All living organisms are composed of fundamental units called cells. Within cells, four major classes of biological macromolecules serve as the building blocks:

• Nucleic acids (e.g., DNA, RNA)

• Lipids (e.g., fats, oils, phospholipids)

• Carbohydrates (e.g., glucose, starch, cellulose)

• Proteins (e.g., enzymes, structural proteins)

These macromolecules are polymers made from smaller subunits called monomers.

Proteins: Structure and Function

Proteins are found throughout the cell and perform a wide variety of functions. Their structure is organized into four levels:

• Primary structure: Sequence of amino acids in a polypeptide chain.

• Secondary structure: Local folding into alpha-helices and beta-sheets, stabilized by hydrogen bonds.

• Tertiary structure: Three-dimensional folding due to interactions among R-groups (hydrophobic interactions, disulfide bonds, etc.).

• Quaternary structure: Association of multiple polypeptide subunits.

Factors affecting protein folding include:

• Amino acid sequence

• Interactions between amino acids

• Temperature

• pH

Functions of proteins:

• Structural support (e.g., collagen)

• Transport (e.g., hemoglobin)

• Muscle contraction (e.g., actin, myosin)

• pH regulation

• Energy source (via catabolism)

• Catalysis (enzymes)

Enzymes: Structure, Function, and Regulation

Definition and Properties of Enzymes

Enzymes are biological catalysts, usually proteins, that speed up chemical reactions without being consumed. An exception is the ribozyme, an RNA molecule with catalytic activity. Enzymes are typically named by adding the suffix "-ase" to the substrate or reaction type (e.g., lactase, sucrase, DNAse).

• Enzymes are substrate-specific: they catalyze only specific reactions.

Active Site and Substrate Specificity

The three-dimensional folding of an enzyme creates an active site, a groove or pocket formed by a cluster of amino acids. The active site binds the substrate with high affinity, allowing the enzyme to catalyze a specific reaction.

The Catalytic Cycle of an Enzyme

The catalytic cycle describes how enzymes facilitate reactions:

1. The active site is available for a substrate molecule.

2. The substrate binds to the active site, forming an enzyme-substrate complex.

3. The enzyme catalyzes the conversion of the substrate to products.

4. The products are released, and the enzyme is free to catalyze another reaction.

Mechanism of Enzyme Action

Every chemical reaction requires an input of energy to proceed, called the activation energy (Ea). Enzymes lower the activation energy, making it easier for reactants to reach the transition state and form products. They do this by:

• Orienting substrates correctly

• Straining substrate bonds

• Providing a favorable microenvironment

• Sometimes participating directly in the reaction

Rate of Enzymatic Reactions: The Michaelis-Menten Model

The Michaelis-Menten model describes the relationship between the initial reaction rate () and substrate concentration ():

• At low , the rate is directly proportional to substrate concentration.

• At high , the rate approaches a maximum velocity ().

The Michaelis constant () is the substrate concentration at which the reaction rate is half of :

• Low = high substrate affinity

• High = low substrate affinity

Equation:

Factors Affecting Enzyme Activity

Enzyme activity is influenced by several environmental and chemical factors:

• Temperature: Each enzyme has an optimal temperature (often around 37°C in humans). Higher or lower temperatures can denature the enzyme or reduce activity.

• pH: Most enzymes function best at pH 6-8, but some (e.g., pepsin) work at lower pH.

• Salt concentration: Physiological salt concentrations are optimal for most enzymes; extreme salinity can disrupt enzyme structure.

• Cofactors: Non-protein helpers required for enzyme activity. These can be:

  • Inorganic (e.g., Cu2+, Zn2+, Mn2+)

  • Organic (coenzymes, e.g., vitamins, ATP, S-adenosyl methionine)

Regulation of Enzymatic Reactions

Cells tightly regulate enzyme activity through several mechanisms:

• Competitive inhibition: Inhibitor resembles the substrate and binds to the active site, blocking substrate access. This inhibition is reversible by increasing substrate concentration.

• Noncompetitive inhibition: Inhibitor binds to a site other than the active site, causing a conformational change that reduces enzyme activity. This effect cannot be overcome by increasing substrate concentration.

• Allosteric regulation: Regulatory molecules bind to an allosteric site (not the active site), stabilizing either the active or inactive form of the enzyme. Allosteric enzymes often have multiple subunits and can be regulated by activators or inhibitors.

• Cooperativity: Binding of one substrate molecule increases the affinity of other subunits for the substrate (e.g., oxygen binding to hemoglobin).

• Feedback inhibition: The end product of a metabolic pathway inhibits an enzyme involved early in the pathway, preventing overproduction of the product.

Cellular Energy: Catabolism, Anabolism, and ATP

Catabolic vs. Anabolic Pathways

Metabolic pathways are classified as:

• Catabolic pathways: Break down complex molecules into simpler ones, releasing energy (e.g., breakdown of proteins, glycogen, triglycerides).

• Anabolic pathways: Build complex molecules from simpler ones, consuming energy (e.g., synthesis of proteins, glycogen, triglycerides).

Exergonic vs. Endergonic Reactions

Chemical reactions can be classified by their energy changes:

• Exergonic reactions: Release free energy; spontaneous ().

• Endergonic reactions: Require input of energy; non-spontaneous ().

Equation for free energy change:

ATP: The Energy Currency of the Cell

Adenosine triphosphate (ATP) is the primary energy carrier in cells. Energy is stored in the high-energy phosphate bonds. Hydrolysis of ATP to ADP and inorganic phosphate releases energy:

The standard free energy change for ATP hydrolysis is kcal/mol.

Coupling Reactions

Cells drive endergonic reactions by coupling them to the exergonic hydrolysis of ATP. For example, the synthesis of glutamine from glutamic acid and ammonia is endergonic, but when coupled with ATP hydrolysis, the overall process becomes exergonic and spontaneous.

Summary Table: Types of Enzyme Inhibition

Example: Feedback Inhibition in Amino Acid Synthesis

When the end product (e.g., isoleucine) accumulates, it inhibits the first enzyme in its biosynthetic pathway, preventing unnecessary synthesis and conserving resources.

Additional info:

• Enzyme regulation is essential for maintaining homeostasis and efficient cellular function.

• ATP is regenerated from ADP and phosphate during cellular respiration, primarily in mitochondria.