Module 1: Biochemistry and the Unity of Life – Foundations, Molecules, and Principles

Module 1: Biochemistry and the Unity of Life

Objectives and Scope

This module introduces the foundational concepts of biochemistry, focusing on the molecular basis of life, the chemical and energetic principles underlying biological systems, and the genetic and evolutionary context of living organisms.

• Compare and contrast prokaryotes and eukaryotes.

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

• Identify chiral carbons and explain the role of stereochemistry in biochemistry.

• Introduce major classes of biomolecules and their unique building blocks and linkages.

• Describe life from a thermodynamic perspective.

• Summarize the genetic basis of living organisms and its relation to evolution.

Biochemistry: Definition and Unity

What is Biochemistry?

Biochemistry is the study of life at the molecular level, applying chemical principles to explain biological phenomena. It seeks to uncover the molecular logic and common reactions that underlie all living organisms.

• Molecular level study: Focuses on molecules and their interactions in living systems.

• Chemical principles: Uses chemistry to explain biological processes.

• Common reactions: Identifies universal biochemical pathways.

• Molecular logic: Explores how molecular structures and functions give rise to life.

Unity of Biochemistry

Despite the diversity in size, shape, and complexity among organisms, there is remarkable molecular uniformity. All organisms use a common set of building blocks and essential biochemical processes.

• Common biomolecules: Nucleic acids, proteins, polysaccharides, and lipids.

• Universal processes: Core metabolic and genetic pathways are conserved.

• Jacques Monod's Principle: "Anything true of E. coli must be true of elephants."

Foundations of Life

Four Pillars of the Living State

Life is considered from four foundational perspectives:

• Chemical

• Energy

• Genetic

• Evolutionary

Chemical Foundations

Elements of Life

Living things are composed of a small set of common elements, primarily carbon, oxygen, hydrogen, and nitrogen, which account for over 96% of most organisms.

• Water: Major source of hydrogen and oxygen in living systems.

• Carbon-based life: All known life forms are built on carbon chemistry.

Element	Human beings (%)	Seawater (%)
Hydrogen	63	66
Oxygen	25.5	33
Carbon	9.5	0.04
Nitrogen	1.4	<0.01
Calcium	0.31	0.06
Phosphorus	0.22	<0.01
Chloride	0.33	1.94
Potassium	0.06	0.04
Sulfur	0.05	0.09
Magnesium	0.01	0.003
Silicon	<0.01	0.01
Aluminum	<0.01	<0.01
Iron	<0.01	<0.01
Titanium	<0.01	<0.01
All others	<0.01	<0.01

Gathering the Building Materials

The essential chemical elements for life are readily available from the environment:

• Carbon: Obtained from air via plants.

• Oxygen: Sourced from air.

• Hydrogen: Derived from water.

• Nitrogen: Abundant in the atmosphere as N2, but biologically available nitrogen comes from plants extracting it from soil.

• Limiting factor: Nitrogen availability in soil limits food production.

Value of Chemical Components

While the raw chemical components of the human body are inexpensive, the organization and complexity of tissues, organs, and biomolecules confer immense value.

• Estimated value: Human body chemicals are worth about $6, but the biological structures are valued at millions.

• Organization: The arrangement of molecules is crucial for life.

Carbon-Based Life

Carbon is the central element in biological molecules due to its versatility in forming stable covalent bonds and complex structures.

• Bonding: Forms four covalent bonds, allowing diverse molecular architectures.

• Stability: Carbon-carbon bonds are stronger and more stable than silicon-silicon bonds.

• Energy: Combustion of carbon-based molecules releases more energy; carbon dioxide is soluble and recyclable in the biosphere.

Functional Groups in Biomolecules

Biomolecules contain various functional groups that determine their chemical properties, reactivity, and interactions.

• Common functional groups: Carboxyl (COOH/COO-), amino (NH2), hydroxyl (OH), phosphate (PO4), etc.

• Properties: Size, charge, reactivity, and hydrogen-bonding capacity vary among groups.

• Protonation states: Functional groups can exist in different protonation states, affecting their behavior.

Structure-Function Relationship

The structure of biomolecules dictates their function. Understanding this relationship is central to biochemistry and enables prediction of molecular function, disease mechanisms, and drug design.

• 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 and chiral centers.

Isomerism and Stereochemistry

Isomers are molecules with the same chemical formula but different arrangements of atoms. Stereochemistry is crucial in biochemistry due to its impact on molecular interactions.

• Geometric (cis-trans) isomers: Differ in arrangement around double bonds.

• Chiral carbons: Carbon atoms with four different substituents, leading to stereoisomers (enantiomers).

• Stereospecificity: Biological systems often use only one stereoisomer (e.g., L-amino acids in proteins).

Biological Importance of Stereochemistry

Stereoisomers can have dramatically different biological activities. For example, the drug thalidomide has two enantiomers, one of which causes birth defects.

• Construction: Biomolecules are built from specific stereoisomers.

• Interactions: Molecular recognition is stereospecific.

Complex Molecules from Simple Precursors

Biomolecules are often polymers of simple building blocks, allowing for simplicity in synthesis and degradation, recycling, and diversity in structure and function.

• Polymers: Proteins, nucleic acids, and polysaccharides are polymers.

• Advantages: Simplicity, recycling, and diversity.

Major Classes of Biomolecules

There are four major classes of biomolecules, each with unique building blocks, linkages, and biological functions.

• Proteins: Linear polymers of amino acids; perform structural, catalytic, and regulatory roles.

• Carbohydrates: Polymers of monosaccharides; serve in energy storage, structure, and recognition.

• Nucleic Acids: Polymers of nucleotides; store and transmit genetic information.

• Lipids: Aggregates of hydrophobic molecules; function in energy storage, membranes, and signaling.

Cellular Foundations

Prokaryotes vs. Eukaryotes

Living organisms are classified as prokaryotes or eukaryotes based on cellular organization.

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

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

Blurred Lines: Human Microbiota

Humans host trillions of prokaryotic cells (microbiota) alongside eukaryotic cells. These bacteria are essential for digestion, immunity, and even mental health.

• Influence: Diet, probiotics, and fecal transplants can affect microbiota composition.

In vitro vs. In vivo Studies

Biochemical studies can be performed in vitro (outside living organisms) or in vivo (within living organisms). In vitro studies simplify experiments but may lack biological relevance.

• In vitro: "In glass"; isolated molecules.

• In vivo: "In the living"; within the complexity of cells and organisms.

Energy Foundations

Energetics of Life

Living requires energy, which is extracted, channeled, and consumed by cells. Biochemistry studies how energy changes drive molecular processes.

• ATP: The universal energy currency of cells.

• Thermodynamics: Cellular energy conversion follows the laws of thermodynamics.

First Law of Thermodynamics

The total energy in the universe remains constant; energy can change forms but is neither created nor destroyed.

• Cells: Convert energy from nutrients or sunlight into work, heat, and biomolecules.

Second Law of Thermodynamics

Natural processes tend toward greater disorder (entropy). Living systems maintain high organization despite this tendency.

• Entropy: Disorder increases in the universe, but cells use energy to maintain order.

Gibbs Free Energy

Gibbs free energy ($G$) determines the spontaneity of chemical reactions. It is defined as:

• $G = H - TS$

• $\Delta G = \Delta H - T\Delta S$

Where $H$ is enthalpy, $S$ is entropy, and $T$ is temperature (Kelvin).

• $\Delta G > 0$: Non-spontaneous (endergonic), requires energy input.

• $\Delta G < 0$: Spontaneous (exergonic), releases energy.

• $\Delta G = 0$: System at equilibrium.

Energy Coupling in Biology

Cells drive unfavorable reactions by coupling them to favorable ones. If the sum of $\Delta G$ for coupled reactions is negative, the overall process is spontaneous.

ATP: The Central Energy Currency

ATP (adenosine triphosphate) links energy-releasing (catabolic) and energy-requiring (anabolic) reactions, serving as the universal energy currency.

Genetic Foundations

Genetic Information and Its Role

Life perpetuates through the stable storage, accurate expression, and faithful reproduction of genetic information, primarily in the form of DNA.

• DNA: Encodes instructions for cellular components and serves as a template for replication.

• Central Dogma: DNA → RNA → Protein (Replication, Transcription, Translation).

Structure of DNA

DNA is a duplex of complementary strands, each a linear polymer of four types of nucleotides. The sequence of bases encodes genetic information.

• Replication: DNA structure allows for accurate copying.

• Information: Sequence of bases is irregular and unrestricted, allowing diversity.

DNA Sequence and Protein Structure

The nucleotide sequence of genes determines the amino acid sequence of proteins, which in turn dictates protein structure and biological activity.

• Genotype to phenotype: DNA → RNA → Protein → Function.

Evolutionary Foundations

Genetic Variation and Evolution

Random changes in genetic information can lead to changes in phenotype. Beneficial changes are selected for, while detrimental ones are selected against.

• Natural selection: Drives evolution by favoring advantageous traits.

• Dobzhansky's Principle: "Nothing in biology makes sense except in the light of evolution."

The Ship of Theseus Analogy

As molecules within an organism are constantly replaced, questions arise about identity and continuity over time.

• Philosophical perspective: Are you the same person as your molecules change?

Additional info: Some explanations and context have been expanded for clarity and completeness, including definitions, examples, and equations.