Module 1: Biochemistry and the Unity of Life

Objectives

• Compare and contrast basic differences and similarities between prokaryotes and eukaryotes.

• Appraise the chemical foundations of life and discriminate basic chemical functional groups.

• Identify chiral carbons and explain how stereochemistry relates to biochemistry.

• Receive introduction to the major classes of biomolecules, including description of their unique building blocks and linkages.

• Describe life from a thermodynamic perspective.

• Summarize the genetic basis of living organisms with consideration of evolution.

Biochemistry: The Molecular Logic of Life

Definition and Scope

• Biochemistry is the study of life at the molecular level.

• It applies the principles of chemistry to explain biological processes.

• It seeks to uncover the common sets of reactions and principles underlying all living organisms.

• Biochemistry reveals the molecular logic of life, explaining how simple chemical principles give rise to complex biological phenomena.

Unity of Biochemistry

Molecular Uniformity Across Life

• Despite differences in size, shape, and complexity, all organisms are remarkably uniform at the molecular level.

• All organisms use a common set of building blocks to create major biomolecules: nucleic acids, proteins, polysaccharides, and lipids.

• There is a common core of essential biochemical processes shared by all life forms.

• Quote: “Anything true of E. coli must be true of elephants.” – Jacques Monod, 1954

Foundations of Life

Four Pillars of the Living State

• Chemical: The elements and molecules that make up living things.

• Energy: How living systems obtain and use energy.

• Genetic: The storage, expression, and transmission of genetic information.

• Evolutionary: How changes in genetic information drive evolution.

Chemical Foundations

Elements of Life

• Living things are composed of a small set of common elements.

• The four most abundant elements in living organisms are carbon (C), oxygen (O), hydrogen (H), and nitrogen (N).

• Water accounts for much of the oxygen and hydrogen in living things.

• All known life forms are carbon-based.

Table: Chemical composition as percentage of total number of atoms in human beings and seawater.

Gathering the Building Materials

• Most chemical elements required for life are readily available:

  • Carbon: from air (via plants)

  • Oxygen: from air

  • Hydrogen: from water

  • Nitrogen: abundant in air as N2, but inert; plants extract usable nitrogen from soil

• The availability of nitrogen in soil often limits plant growth and thus food production.

• Without nitrogen-fixing processes, the natural nitrogen in soil would only support about 4 billion people.

What Are You Worth?

• In 1972, the chemicals in a human body were valued at about $1.00 (about $6 today).

• However, the value of a human is far greater due to the organization and function of tissues, organs, and biomolecules (estimated at $45,000,000).

• The way chemical components are assembled in living things is what gives them immense value.

Carbon: The Foundation of Life

• All life as we know it is carbon-based due to carbon's versatility in forming stable covalent bonds.

• Carbon can form four covalent bonds, allowing for a wide variety of complex molecules.

• Carbon-carbon bonds are stronger and more stable than silicon-silicon bonds, making carbon preferable for life.

• Combustion of carbon-based molecules releases more energy, and the products (CO2) are easily recycled in the biosphere.

Functional Groups in Biomolecules

• Biomolecules contain a variety of functional groups (e.g., hydroxyl, carboxyl, amino, phosphate).

• Functional groups determine the structure, reactivity, and properties of biomolecules.

• They can exist in different protonation states (e.g., COO- vs. COOH).

Structure-Function Relationship

• The structure of a biomolecule dictates its function.

• Understanding structure-function relationships allows prediction of molecular function and the development of treatments.

• Conformation: Flexible spatial arrangement of atoms (can change without breaking covalent bonds).

• Configuration: Fixed spatial arrangement (cannot change without breaking covalent bonds), determined by double bonds or chiral centers.

Isomerism in Biomolecules

• Geometric (cis-trans) isomers: Same formula, different arrangement around a double bond.

• Cis: Groups on the same side; Trans: Groups on opposite sides.

• These isomers can have very different biological properties, especially in proteins and lipids.

• Chiral carbons: Carbon atoms with four different substituents, leading to stereoisomers with distinct biological activities.

Stereospecificity in Biochemistry

• Biochemistry is highly stereospecific: biomolecules are usually constructed from one stereoisomer (e.g., proteins from L-amino acids).

• Interactions between biomolecules are also stereospecific.

• Drugs with chiral centers may have different effects depending on the isomer (e.g., thalidomide).

Polymers and Biomolecular Diversity

• Biomolecules are often polymers of simple building blocks.

• Advantages of polymer construction:

  • Simplicity: Conserved reactions for synthesis and degradation.

  • Recycling: Building blocks can be reused.

  • Diversity: Complex molecules can be generated from simple units.

Major Classes of Biomolecules

• Proteins: Linear polymers of 20 different amino acids; perform diverse biological functions.

• Carbohydrates: Monosaccharides linked to form polysaccharides; roles in structure, energy storage, and recognition.

• Nucleic Acids: Polymers of nucleotides; involved in storage and utilization of genetic information.

• Lipids: Aggregates of building blocks; serve in energy storage, membranes, and signaling.

Cellular Foundations

Prokaryotes vs. Eukaryotes

• Prokaryotes: Small, simple, single-celled organisms (e.g., bacteria); rapid growth; single compartment (nucleoid).

• Eukaryotes: Larger, complex cells; make up multicellular organisms; contain organelles (nucleus, mitochondria, etc.); specialized cell types.

• Humans contain both eukaryotic and prokaryotic cells (microbiota), which are essential for health.

In Vitro vs. In Vivo

• In vitro ("in glass"): Studies molecules outside the context of the cell/organism; simplifies experiments but may lack biological relevance.

• In vivo ("in the living"): Studies within the complexity of the cell/organism; more biologically significant.

• Experiments successful in vitro may not always work in vivo.

Energy Foundations

Energy and Life

• Living is energetically expensive; energy must be obtained from the environment.

• Cells extract, channel, and consume energy for work, heat, and synthesis of biomolecules.

• Cellular energy conversion is governed by the laws of thermodynamics.

First Law of Thermodynamics

• Energy cannot be created or destroyed; it can only change forms.

• Cells convert energy from nutrients or sunlight into work, heat, or complex molecules.

Second Law of Thermodynamics

• Natural processes tend toward greater disorder (increasing entropy).

• Living systems maintain high organization despite this tendency.

Gibbs Free Energy

• Free energy (G) determines whether a process is spontaneous.

• Defined as: where H = enthalpy, T = temperature (Kelvin), S = entropy.

• Change in free energy:

• Interpretation:

  • : Non-spontaneous (endergonic), requires energy input.

  • : Spontaneous (exergonic), releases energy.

  • : System at equilibrium.

Energy Coupling and ATP

• Cells couple unfavorable (endergonic) reactions to favorable (exergonic) ones to drive necessary processes.

• The sum of free energy changes must be negative for the overall process to be spontaneous.

• ATP (adenosine triphosphate) is the central energy currency, linking catabolic and anabolic reactions.

Genetic Foundations

Genetic Information and the Central Dogma

• Genetic information must be stored, expressed, and reproduced with high fidelity.

• In most organisms, DNA stores genetic instructions and serves as a template for replication.

• The Central Dogma of biochemistry: DNA → RNA → Protein

• Each DNA strand is a linear polymer of four types of nucleotides; the sequence encodes information.

• The sequence of nucleotides in DNA determines the sequence of amino acids in proteins, which in turn determines protein structure and function.

Evolutionary Foundations

Genetic Variation and Evolution

• Random changes in genetic information (mutations) can result in changes in phenotype (observable characteristics).

• If a change offers an advantage, it is selected for; if disadvantageous, it is selected against.

• Evolution is the process by which populations of organisms change over generations through changes in genetic information.

• Quote: “Nothing in biology makes sense except in the light of evolution.” – Theodosius Dobzhansky, 1973

The Ship of Theseus: Identity and Change

• As molecules within an organism are constantly replaced, questions arise about the persistence of identity over time.

• This philosophical question highlights the dynamic nature of living systems.