Chemistry in Biological Systems

The Role of Chemistry in Living Systems

Living organisms are complex chemical systems. What distinguishes them from non-living matter is not the presence of unique elements, but the way common elements (especially C, H, O, N, P, S and various metals) are organized into specific molecules and reaction networks.

This chapter introduces how organic chemistry “comes alive” in cells: how biomolecules are arranged in space and time, how reactions are coupled and regulated, and how this leads to emergent properties such as metabolism, growth, and information storage. Detailed mechanisms of metabolism, photosynthesis, respiration, and fermentation are addressed in later chapters of this section; here, we outline the overarching chemical logic of biological systems.

Key Characteristics of Chemical Processes in Cells

Aqueous, Mild, and Highly Organized Conditions

All known life operates in water, at relatively mild temperatures and near-neutral pH:

• Solvent: water as the universal medium.
• Temperature: often between about $0{-}50^\circ\mathrm{C}$.
• pH: commonly near neutral, with controlled variations in specialized compartments (e.g. stomach acid, lysosomes).
• Concentrations: many solutes in the $10^{-3}$ to $10^{-9}\,\mathrm{mol\,L^{-1}}$ range.

Despite these mild conditions, cells manage reactions that would be sluggish or impossible in a simple beaker of water. This is possible because:

• Reactants are compartmentalized (organelles, membranes).
• Reactions are catalyzed mainly by enzymes.
• There is precise regulation of when and where reactions occur.

Compartmentalization and Microenvironments

Biological chemistry is spatially structured:

• Membranes create separated spaces (e.g. cytosol vs. mitochondria).
• Organelles provide specialized reaction conditions.
• Protein scaffolds and multi-enzyme complexes channel intermediates from one active site to another (“substrate channeling”).

As a result, the same type of molecule can participate in different processes depending on where it is located and with which partners it interacts.

Selectivity and Specificity

Biological chemistry is extremely selective:

• Substrate specificity: most enzymes catalyze only one reaction type for a narrow range of substrates.
• Stereospecificity: enzymes distinguish between stereoisomers (e.g. D- vs. L-sugars, R- vs. S-centers).
• Regiospecificity: bonds are formed or broken at defined positions of a molecule.

This selectivity stems from the precise 3D arrangement of atoms in enzymes, receptors, and other biomolecular structures.

Biomolecules as Building Blocks and Functional Units

Other chapters cover the structures and reactions of carbohydrates, fats (lipids), amino acids, and nucleic acids in detail. Here, we focus on how these classes of organic compounds combine to create functional systems in cells.

Structural Roles

Many biomolecules act primarily as structural materials:

• Proteins: cytoskeleton filaments, extracellular matrix, connective tissue (e.g. collagen, keratin).
• Polysaccharides: cellulose in plant cell walls, chitin in exoskeletons, peptidoglycan in bacterial walls.
• Lipids: phospholipid bilayers in biological membranes; cholesterol and related lipids modulating membrane fluidity.

The underlying chemistry includes:

• Polymerization via condensation reactions (e.g. peptide bond formation, glycosidic bonds).
• Noncovalent interactions (hydrogen bonds, van der Waals forces, ionic interactions, hydrophobic effect) organizing higher-order structures (e.g. membranes, protein folding).

Functional and Regulatory Roles

Beyond structure, biomolecules serve dynamic roles:

• Enzymes: proteins (and some RNAs) that catalyze biological reactions.
• Transporters: proteins transporting ions, metabolites, and macromolecules across membranes or within cells.
• Signaling molecules: hormones, neurotransmitters, second messengers (e.g. cAMP), which are often small organic molecules or modified lipids/peptides.
• Information carriers: nucleic acids (DNA, RNA) encoding and transmitting genetic information.

Here the key is how small changes in structure (e.g. a phosphate group attached to a protein, a double bond configuration, or a minor side-chain modification) can drastically change function.

Energetics and Coupling of Reactions in Biology

Many reactions essential for life are thermodynamically unfavorable under cellular conditions; they will not proceed spontaneously in the desired direction. Cells solve this by coupling reactions.

Reaction Coupling

A coupled reaction combines a thermodynamically unfavorable process with a favorable one so that the overall change in Gibbs free energy is negative:

$$
\Delta G_\text{total} = \Delta G_1 + \Delta G_2 < 0
$$

Common examples include:

• Coupling biosynthetic (anabolic) reactions to the hydrolysis of $ \mathrm{ATP} $.
• Driving ion transport against a gradient using energy from redox reactions.
• Using light energy to generate high-energy intermediates (in photosynthesis).

The details of Gibbs free energy and thermodynamics are handled elsewhere; what matters here is that biological systems organize reactions into networks where energy-releasing processes continuously fuel energy-requiring ones.

Energy Carriers

Cells use specific molecules as “energy currencies” or carriers:

• ATP and other nucleoside triphosphates: their hydrolysis is highly exergonic and can be directly coupled to many chemical transformations (phosphorylations, conformational changes of proteins, etc.).
• Reduced coenzymes (e.g. NADH, NADPH, FADH$_2$): carry pairs of electrons and often protons; central to redox reactions.
• Ion gradients (e.g. $\mathrm{H^+}$, $\mathrm{Na^+}$): represent stored potential energy across membranes, convertible into ATP or work (e.g. rotation of molecular motors).

These carriers link different parts of metabolism: energy from catabolism (oxidation of nutrients) is packaged in forms that can be used by anabolism and by cellular work (movement, transport, synthesis).

Catalysis by Enzymes and Coenzymes

Enzymes as Biological Catalysts

Most biochemical transformations would be far too slow under cellular conditions without catalysis. Enzymes:

• Increase reaction rates by many orders of magnitude.
• Do not change the overall $\Delta G$ of the reaction.
• Operate under mild conditions and exhibit high specificity.

Common features:

• An active site where substrates bind and transition states are stabilized.
• Use of acid–base catalysis, nucleophilic/electrophilic catalysis, and metal ion catalysis, analogous in principle to reactions from general organic chemistry.
• Conformational dynamics, where binding of substrate induces shape changes that facilitate reaction and product release.

Coenzymes and Metal Ions

Many enzymes require small organic or inorganic helpers:

• Coenzymes/cofactors: small organic molecules (often vitamin-derived) that participate directly in the chemical transformation (e.g. NAD$^+$/NADH in hydride transfer, CoA in acyl group transfer).
• Prosthetic groups: tightly bound non-protein components (e.g. heme in cytochromes).
• Metal ions: $\mathrm{Mg^{2+}}$, $\mathrm{Zn^{2+}}$, $\mathrm{Fe^{2+}/Fe^{3+}}$, etc., stabilizing charges or participating in redox processes.

From an organic-chemistry viewpoint, these cofactors often provide specialized reactive centers (e.g. conjugated systems, thioesters, imines, phosphoanhydrides) that enable transformations otherwise difficult for amino acid side chains alone.

Chemical Networks: Metabolism as an Integrated System

Metabolism is the sum of all chemical reactions in a living system, organized into pathways and networks.

Catabolism and Anabolism

• Catabolism: degradation of energy-rich molecules (e.g. carbohydrates, fats) into smaller units, often yielding $\mathrm{CO_2}$, $\mathrm{H_2O}$, and energy carriers (ATP, NADH).
• Anabolism: synthesis of complex biomolecules (proteins, nucleic acids, lipids, polysaccharides) from small precursors, consuming ATP and reducing equivalents (e.g. NADPH).

Chemically, catabolic pathways often involve sequential oxidations, cleavages, and isomerizations; anabolic pathways frequently feature reductions, condensations, and group transfers.

Pathways, Cycles, and Branch Points

Reactions are not isolated; they form patterns:

• Linear pathways: product of one enzyme is substrate for the next (e.g. many degradation sequences).
• Cycles: sets of reactions regenerating a starting compound (e.g. metabolic cycles).
• Branched networks: intermediates diverted into multiple fates (e.g. central metabolites feeding both energy production and biosynthesis).

From a chemical perspective, this organization:

• Minimizes the need for many unrelated starting materials.
• Reuses a limited set of key intermediates (e.g. certain 2-, 3-, 4-, 5-, and 6-carbon compounds).
• Allows coherent control over large numbers of reactions via a few regulatory molecules.

Regulation of Metabolic Flux

The rates at which pathways operate (metabolic fluxes) are tightly regulated:

• Allosteric regulation: small molecules bind enzymes at regulatory sites, modulating activity (activation or inhibition).
• Covalent modification: reversible changes such as phosphorylation/dephosphorylation alter enzyme activity or localization.
• Feedback inhibition: end products of a pathway inhibit enzymes early in that pathway, preventing overproduction.
• Gene expression control: synthesis and degradation of enzymes adjust the long-term capacity of pathways.

These regulatory mechanisms apply concepts from chemical kinetics and equilibria in a coordinated way, using molecular recognition and binding equilibria to fine-tune reaction velocities.

Information Storage and Transfer: A Chemical Perspective

Biological information is encoded chemically:

• DNA: a polymer of nucleotides; sequence of bases encodes genetic information.
• RNA: transcribes and helps translate this information into proteins.
• Proteins: their amino acid sequences determine 3D structures and functions.

From the standpoint of organic chemistry:

• Information is stored in the sequence of monomer units (nucleotides, amino acids).
• Base pairing is a specific pattern of hydrogen bonding and stacking in nucleic acids.
• Replication, transcription, and translation are highly orchestrated sequences of condensation and hydrolysis reactions, guided by complementary binding and enzyme catalysis.

The key principle is that specific noncovalent interactions (especially hydrogen bonds and shape complementarity) allow molecules to “recognize” each other and assemble in defined ways, enabling faithful information transfer.

Chemical Communication and Signaling

Cells communicate using chemical signals on various scales:

• Intracellular signaling: small molecules or modified proteins transmit information within a cell (e.g. phosphorylation cascades).
• Intercellular signaling: hormones, neurotransmitters, and growth factors diffuse or are transported to target cells.
• Environmental sensing: receptors detect external molecules (nutrients, toxins, signals from other organisms).

Chemically, signaling involves:

• Ligand–receptor interactions: highly specific binding events governed by noncovalent forces and equilibrium constants.
• Signal amplification: one binding event triggers many downstream reactions (e.g. enzyme cascades), often via controlled changes in reaction rates or equilibria.
• Reversible modifications: transient covalent changes (phosphorylation, acetylation, etc.) serve as “switches” that turn processes on and off.

This shows how simple principles of binding equilibria and kinetics, applied to complex networks, give rise to coordinated behavior at the cellular and organismal levels.

Emergent Properties of Biological Chemical Systems

When many reactions, molecules, and regulatory mechanisms interact, new properties emerge that are not obvious from individual reactions alone:

• Homeostasis: stabilization of internal conditions (pH, ion levels, metabolite concentrations) despite external changes, via feedback-controlled reaction networks.
• Self-replication: coordinated synthesis of all components necessary to produce a new cell, driven by templated polymerization of DNA and other macromolecules.
• Adaptation and evolution: small chemical changes (mutations, modifications) can alter metabolic or signaling pathways; selection of advantageous variants shapes biochemical networks over time.

From an educational standpoint, chemistry in biological systems illustrates how the same fundamental chemical principles—bonding, thermodynamics, kinetics, equilibria, and catalysis—underlie highly complex, ordered, and adaptive behavior when applied in a structured, hierarchical way.

This chapter has outlined the general chemical logic of living systems. The subsequent chapters in this section explore specific examples: how metabolism harnesses and transforms energy, how photosynthesis and respiration are specialized energy conversion strategies, and how different modes of dissimilation operate chemically in cells.