Principles of Biochemistry

1. Cells Rely on Weak Interactions and Water's Unique Properties

The interplay among the chemical components of a living organism is dynamic; changes in one component cause coordinating or compensating changes in another, with the whole ensemble displaying a character beyond that of its individual parts.

Water's solvent role. Water, comprising 70% or more of a cell's weight, is crucial due to its unique properties arising from hydrogen bonding. These bonds create cohesion, high surface tension, and solvent capabilities, allowing polar biomolecules to dissolve and interact dynamically within cells.

Weak forces define life. Individually weak, noncovalent interactions such as hydrogen bonds, ionic interactions, hydrophobic interactions, and van der Waals forces collectively dictate the structure and function of biomolecules. These interactions are essential for the dynamic interplay between cellular components.

Dynamic equilibrium. Living organisms exist in a dynamic steady state, constantly exchanging matter and energy with their surroundings. This state, far from equilibrium, is maintained by the constant investment of energy and the interplay of chemical components, showcasing the remarkable properties of living matter.

2. Carbon's Versatility Underpins the Diversity of Biomolecules

The chemical “personality” of a compound is determined by the chemistry of its functional groups and their disposition in three-dimensional space.

Carbon's bonding prowess. Carbon's ability to form stable bonds with itself and other elements, creating diverse molecular architectures, is fundamental to life. These carbon skeletons, adorned with various functional groups, give rise to the vast array of biomolecules with specific chemical properties.

Functional groups define properties. Functional groups such as hydroxyl, amino, carbonyl, and carboxyl groups dictate the chemical behavior of biomolecules. The arrangement of these groups in three-dimensional space further refines their properties, influencing their interactions and biological roles.

From hydrocarbons to life. Most biomolecules can be viewed as derivatives of hydrocarbons, with hydrogen atoms replaced by functional groups. This chemical versatility allows for the creation of molecules with widely different sizes, shapes, and chemical characteristics, essential for the molecular machinery of cells.

3. Life's Building Blocks Assemble into Complex Hierarchies

A single bacterial cell placed in a sterile nutrient medium can give rise to a billion identical “daughter” cells in 24 hours.

Monomers to macromolecules. Small organic molecules, including amino acids, nucleotides, and sugars, polymerize to form macromolecules like proteins, nucleic acids, and polysaccharides. These macromolecules, in turn, assemble into supramolecular complexes, creating a structural hierarchy within cells.

Noncovalent assembly. While monomers are linked by covalent bonds, supramolecular complexes are held together by noncovalent interactions. These weak interactions, including hydrogen bonds, ionic interactions, hydrophobic interactions, and van der Waals forces, collectively stabilize the assemblies.

In vitro vs. in vivo. Studying purified molecules in vitro provides valuable insights, but it's crucial to remember that the cellular environment is far more complex. Interactions with other molecules and the organization of the cytoplasm can significantly influence a molecule's function in vivo.

4. Thermodynamics Dictates Energy Flow in Living Systems

We can classify organisms according to how they obtain the energy and carbon they need for synthesizing cellular material.

Open systems. Living organisms are open systems, exchanging both matter and energy with their surroundings. They derive energy from sunlight (phototrophs) or chemical compounds (chemotrophs), using it to build and maintain their intricate structures.

Laws of thermodynamics. The first law dictates that energy is conserved, while the second law states that the universe tends towards increasing disorder (entropy). Living organisms maintain order by extracting energy from their surroundings and releasing heat and simpler compounds, increasing entropy in the universe.

Free energy and spontaneity. The free-energy change (ΔG) determines the spontaneity of a process. Exergonic reactions (negative ΔG) release energy, while endergonic reactions (positive ΔG) require energy input. Cells couple exergonic reactions, such as ATP hydrolysis, to drive endergonic processes.

5. Enzymes Catalyze Reactions by Lowering Activation Energy

Virtually every chemical reaction in a cell occurs at a significant rate only because of the presence of enzymes—biocatalysts that, like all other catalysts, greatly enhance the rate of specific chemical reactions without being consumed in the process.

Enzymes as catalysts. Enzymes are biological catalysts that accelerate specific chemical reactions without being consumed in the process. They achieve this by lowering the activation energy (ΔG‡), the energy barrier between reactants and products.

Transition state stabilization. Enzymes catalyze reactions by providing a more comfortable fit for the transition state, the highest-energy intermediate in the reaction. This complementary fit, based on stereochemistry, polarity, and charge, reduces the activation energy and increases the reaction rate.

Metabolic pathways. Enzymes are organized into pathways, sequences of consecutive reactions in which the product of one reaction becomes the reactant in the next. These pathways are either catabolic (degradative, energy-yielding) or anabolic (synthetic, energy-requiring), and their activity is tightly regulated to maintain balance and economy.

6. DNA's Structure Enables Accurate Replication and Information Storage

The capacity of living cells to preserve their genetic material and to duplicate it for the next generation results from the structural complementarity between the two halves of the DNA molecule.

DNA as the blueprint. DNA, a linear polymer of nucleotides, stores and transmits the genetic information necessary for building and maintaining an organism. The sequence of nucleotides encodes the instructions for forming all other cellular components.

Double helix complementarity. The double-helical structure of DNA, with its complementary base pairing (A with T, G with C), allows for accurate replication and repair. Each strand serves as a template for the synthesis of a new complementary strand.

From DNA to protein. The information in DNA is expressed through a two-step process: transcription, where DNA is copied into RNA, and translation, where RNA is used to direct the synthesis of proteins. Proteins, with their unique three-dimensional structures, carry out most of the functions in a cell.

7. Evolution Explains the Unity and Diversity of Life at the Molecular Level

The remarkable similarity of metabolic pathways and gene sequences in organisms across the phyla argues strongly that all modern organisms share a common evolutionary progenitor and were derived from it by a series of small changes (mutations), each of which conferred a selective advantage to some organism in some ecological niche.

Mutations drive evolution. Infrequent errors in DNA replication lead to mutations, changes in the nucleotide sequence. While most mutations are harmful, some can provide a selective advantage, allowing the organism to better survive and reproduce in its environment.

Chemical evolution. Before the first cells, biomolecules likely arose through chemical evolution, with simple organic compounds forming spontaneously under the conditions of early Earth. RNA, with its ability to both store information and catalyze reactions, may have played a crucial role in this prebiotic evolution.

Common ancestry. The universality of metabolic pathways and gene sequences across diverse organisms points to a shared evolutionary origin. Adaptive selection, combined with genetic variation, has resulted in the vast diversity of life forms we see today, each adapted to its specific ecological niche.

Last updated: April 18, 2025