Module 1: Biochemistry and the Unity of Life – Foundations for Anatomy & Physiology

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 the unique building blocks and linkages within each class.

• Describe life from a thermodynamic perspective.

• Summarize the genetic basis of living organisms with consideration of how this relates to evolution.

Introduction to Biochemistry

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 understand the common sets of reactions and principles that underlie all living organisms.

• Biochemistry explores the molecular logic of life.

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 repertoire of building blocks to create major biomolecules: nucleic acids, proteins, polysaccharides, and lipids.

• There is a common core of essential biochemical processes across 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 things obtain and use energy.

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

• Evolutionary: How genetic changes drive evolution and diversity.

Chemical Foundations

Elements of Life

Living things are composed of a small set of common elements. The most abundant elements in living organisms are hydrogen, oxygen, carbon, and nitrogen, which together account for over 99% of most organisms' mass.

Element	Human Beings (%)	Seawater (%)
Hydrogen	63	66
Oxygen	25.5	33
Carbon	9.5	0.04
Nitrogen	1.4	<0.01
Calcium	0.31	0.006
Phosphorus	0.22	<0.01
Chloride	0.33	1.92
Potassium	0.06	0.07
Sulfur	0.05	0.01
Magnesium	0.01	0.003
Silicon	<0.1	0.01
Aluminum	<0.1	<0.1
Iron	<0.1	<0.1
Titanium	<0.1	<0.1
All others	<0.1	<0.1

Additional info: Table compares the elemental composition of humans and seawater, highlighting the prevalence of hydrogen and oxygen in both, but a much higher carbon content in humans.

Gathering the Building Materials

• Most elements required for life are readily available: carbon (from air via plants), oxygen (from air), and hydrogen (from water).

• Nitrogen is abundant in the atmosphere as N2, but is inert and must be fixed by plants or bacteria to be usable by living organisms.

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

• Without nitrogen fixation, the natural amount of nitrogen in soil would only support about 4 billion people.

Value of Biological Materials

• The chemical elements in a human body are worth only a few dollars, but the value of tissues, organs, and biomolecules is estimated at millions.

• The way these components are organized and interact is what gives life its true value.

Carbon: The Basis of Life

• All known life forms are carbon-based due to carbon's ability to form four covalent bonds, allowing for a vast diversity of stable, complex molecules.

• Carbon-carbon bonds are stronger and more stable than silicon-silicon bonds, making carbon preferable as the backbone of biomolecules.

• Combustion of carbon-based molecules releases more energy, and the product (CO2) is soluble and recyclable in the biosphere.

Functional Groups in Biomolecules

• Biomolecules contain a variety of functional groups (e.g., hydroxyl, carboxyl, amino, phosphate, etc.), each with unique size, charge, reactivity, and hydrogen-bonding capacity.

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

• The properties of functional groups determine the structure, function, and properties of biomolecules.

Structure-Function Relationship

• The structure of a biomolecule dictates its function.

• Understanding structure-function relationships allows prediction of molecular function, understanding of pathology, and rational drug design.

Conformation vs. Configuration

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

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

Isomerism in Biomolecules

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

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

• Geometric 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.

Stereochemistry and Biological Specificity

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

• Interactions between biomolecules are also stereospecific.

• Synthesis of drugs with chiral centers can result in mixtures with different biological effects (e.g., thalidomide enantiomers).

Polymers and Biomolecular Diversity

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

Major Classes of Biomolecules

• Proteins: Linear polymers of 20 different amino acids; function in catalysis, structure, signaling, and more.

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

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

• Lipids: Aggregates of building blocks (not true polymers); serve in energy storage, membrane structure, 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 with organelles (nucleus, mitochondria, etc.); make up multicellular organisms; specialized cell types.

Blurred Lines: Human Microbiota

• The human body contains both eukaryotic and prokaryotic cells (microbiota).

• Prokaryotic cells in the gut are essential for digestion, immune function, and may influence obesity, intelligence, and mental health.

• Microbiota can be influenced by diet, probiotics, and fecal transplants.

In Vitro vs. In Vivo Studies

• 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 but complex.

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

Energy Foundations

Energy and Life

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

• Cells extract, channel, and consume energy, primarily in the form of ATP.

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

First Law of Thermodynamics

• Energy cannot be created or destroyed, only transformed.

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

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) of a system is defined as:

$G = H - TS$

• Where H = enthalpy, T = temperature (Kelvin), S = entropy.

• The change in free energy is:

$\Delta G = \Delta H - T\Delta S$

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

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

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

Energy Coupling and ATP

• Cells couple endergonic (energy-requiring) and exergonic (energy-releasing) reactions to drive unfavorable processes.

• ATP (adenosine triphosphate) serves as the universal energy currency, linking catabolic and anabolic reactions.

Genetic Foundations

Genetic Information and Its Role

• Genetic information must be stored stably, expressed accurately, and reproduced with minimal errors.

• DNA provides instructions for forming cellular components and serves as a template for replication.

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

Structure and Replication of DNA

• DNA is a duplex of complementary strands; each strand is a linear polymer of four types of nucleotides.

• The sequence of bases encodes genetic information and is not restricted in its order.

From Genes to Proteins

• The nucleotide sequence of genes determines the amino acid sequence of proteins.

• The amino acid sequence dictates protein structure, which in turn determines biological activity.

Evolutionary Foundations

Genetic Variation and Evolution

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

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

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

Ship of Theseus: Identity and Change

• Over time, all molecules in an organism are replaced; raises philosophical questions about identity and continuity.