Introduction to Biochemistry (Lecture Notes)

What is biochemistry? Core questions and scope

• Biochemistry answers three overarching questions about living systems:
  • Of what are living organisms made?
  • How do organisms acquire and use energy?
  • How does an organism maintain its identity across generations?
• From these questions we study biomolecules (biopolymers) and how they fit together, how energy flow is managed, and how genetic information is stored, transmitted, and used to build functional molecules.
• The course emphasizes both covalent chemistry and noncovalent interactions (intermolecular forces) as essential to understanding biomolecular behavior.
• Biochemistry sits at the intersection of biology and chemistry: it uses general and organic chemistry principles to explain biological phenomena.

Three fundamental questions in biochemistry

• What are living organisms made of?
  • Leads to discussion of biomolecule classes: proteins, nucleic acids, carbohydrates, lipids.
  • Emphasis on polymers (except some lipid categories) and how monomeric units assemble into larger structures.
• How do organisms acquire and use energy?
  • Covers energy transformation, not just intake, but conversion into usable forms for work.
  • Introduces thermodynamics concepts needed to analyze energy flow in cells.
• How do organisms maintain identity across generations?
  • Focus on nucleic acids (DNA and RNA) and the molecular basis of inheritance.
  • Sets up the central dogma: how information flows from DNA to RNA to protein.

Biomolecules, polymers, and residues

• Polymers in biology (biopolymers): proteins, nucleic acids, and carbohydrates are polymers made from monomeric units connected by covalent bonds.
• Lipids are a broader category that includes fats, oils, cholesterol, and related molecules; many lipids are not polymers and rely heavily on noncovalent interactions for organization.
• In biochemistry, the term residue is the biopolymer monomeric unit (the monomer within a polymer).
• Biopolymers are versatile: they serve catalytic, energetic, informational, and structural roles.
• Representative examples:
  • Proteins: workhorses of biology (enzymes, structural roles, sometimes energy storage).
  • Nucleic acids: DNA encodes genetic information; RNA participates in gene expression and sometimes catalysis.
  • Carbohydrates: sugars; glycogen as an energy storage polymer.
  • Lipids: membrane structure (lipid bilayers) and energy storage; often noncovalently organized.
• For visual simplicity, biomolecules are often drawn schematically rather than showing every atom; functional group context explains properties and reactivity.

Elements in biology and the periodic table in biochemistry

• Although the periodic table contains many elements, biology predominantly uses a small subset:
  • Organic elements (most abundant in biomolecules): Hydrogen (H), Oxygen (O), Carbon (C), Nitrogen (N).
  • Abundances in the human body (approximate by atom count):
  • Carbon: ≈ 10%
  • Oxygen: ≈ 25%
  • Hydrogen: > 60%
  • Nitrogen: ≈ 1.5%
  • Trace elements: silicon (Si), aluminum (Al), iron (Fe), titanium (Ti), cobalt (Co), nickel (Ni) — required in only very small amounts but essential.
  • Other essential elements: calcium (Ca), phosphorus (P), potassium (K), etc.
• Practical note: Review acids/bases, kinetics, molecular shapes, polarity from general chemistry; review functional groups and mechanisms from organic chemistry.
• In biomolecules, functional groups are key to identification and understanding behavior; many functional groups recur in different biomolecules with context-specific roles.

Functional groups: what you should recognize

• Amine groups: can be primary, secondary, or tertiary depending on the number of carbon substituents on nitrogen.
• Alcohols (hydroxyl groups): –OH attached to a carbon.
• Thiols: –SH groups (sulfur analog of alcohols).
• Ethers: C–O–C linkages.
• Aldehydes: carbonyl at the end of a carbon chain (–CHO).
• Ketones: carbonyl in the middle of a chain (–CO–).
• Carboxylic acids: –COOH, with a proton that can be donated or retained; protonated vs deprotonated forms:
  • Protonated: –COOH
  • Deprotonated (carboxylate): –COO⁻ (negative charge on the oxygen).
• Esters: carbonyl with an adjacent alkoxy group (R–O–C(=O)–R').
• Amides: carbonyl with a nitrogen; can be primary, secondary, or tertiary depending on N-substituents.
• Imines: C=N functional group.
• Phosphoesters (phosphoric acid esters): a phosphorus–oxygen double bond with adjacent hydroxyl groups; key in nucleotide backbones.
• Diphosphoric acid esters (phosphodiesters): two phosphoester units linked by an bridging oxygen; analogous in function to anhydrides in organic chemistry.
• Why this matters: knowing these groups by sight helps predict reactivity, polarity, hydrogen bonding, and interactions in biomolecules.
• Practical tip: maintain flashcards or diagrams to quickly identify functional groups in complex biomolecules.

Biopolymers and their monomeric units

• Biopolymers are built from repeating units (monomers) linked covalently to form long chains.
• The term residue refers to the monomeric unit within a biopolymer.
• Major biopolymer classes and representative monomer types:
  • Proteins: made of amino acid residues; enzymes serve as catalysts and can store energy in some contexts.
  • Nucleic acids: DNA and RNA; nucleotides form polymers that store and convey genetic information; RNA also participates in catalysis and regulation.
  • Carbohydrates: monosaccharides linked to form polysaccharides like glycogen (energy storage) and structural polysaccharides.
  • Lipids: diverse molecules (fats, phospholipids, sterols); not classical polymers but form organized structures (e.g., membranes) via noncovalent interactions.
• A key contrast: proteins, nucleic acids, and carbohydrates form polymers with covalent backbones; lipids rely more on noncovalent interactions and hydrophobic effects for organization.
• Common visual motif: cartoon representations emphasize overall shape and connectivity rather than every atom.

The central dogma and flow of information

• Central dogma: DNA -> RNA -> Protein; three core steps:
  • Replication: copying DNA so genetic information is preserved and transmitted.
  • Transcription: copying a DNA segment into RNA; not all of DNA is transcribed.
  • Translation: RNA is used as a template to synthesize proteins; protein products perform cellular functions (phenotype).
• Important nuance: lipids are not part of the central dogma flow but are essential for cell structure and function (membranes, signaling, energy storage).
• Relationship recap: DNA stores information, RNA serves as a working template and sometimes a catalyst, protein executes function; collectively, these processes translate genetic information into cellular phenotype.
• Glycogen as carbohydrate example: a storage polymer for sugars within the body.

Lipids, membranes, and the hydrophobic effect

• Lipids form a barrier that defines the cell interior from the external environment: membranes are critical for cellular life.
• Lipid bilayer: amphiphilic molecules with polar head groups (hydrophilic) and nonpolar tails (hydrophobic).
• In bilayers:
  • Hydrophobic tails seek to avoid water and cluster inside the bilayer.
  • Polar head groups face outward toward the aqueous environments.
  • This arrangement creates a nonpolar core that water and many solutes cannot easily cross.
• Result: two distinct aqueous environments inside and outside the cell are maintained by the membrane, enabling controlled chemistry and compartmentalization.
• Practical implication: lipid bilayers create selective permeability and are central to cell integrity and signaling.

Energy, thermodynamics, and free energy in biology

• Fundamental conservation: energy cannot be created or destroyed; it can be transformed.
• Free energy concept: the usable energy available to perform work in a system.
• Enthalpy (ΔH) is a measure of heat content; at constant pressure (as in biological systems), ΔH corresponds to heat exchange.
• Entropy (ΔS) is a measure of energy dispersion or disorder; higher dispersion means less usable energy for doing work.
• Gibbs free energy: $\boxed{ riangle G = riangle H - T riangle S }$
  • ΔG < 0: spontaneous process
  • ΔG > 0: nonspontaneous process (requires input of energy or coupling to other reactions)
• Reaction coordinate vs potential energy diagram:
  • A->B: requires energy input (ΔG > 0) and may not proceed spontaneously as a single step.
  • B->C: releases energy (ΔG < 0) and can proceed spontaneously.
  • Overall A->C can be spontaneous if ΔG ext{overall} = ΔG1 + ΔG2 < 0.
• Example of coupled reactions (-driving nonspontaneous by spontaneous):
  • Suppose ΔG1 = +15 kJ and ΔG2 = -20 kJ; overall ΔG = $+15 + (-20) = -5 ext{ kJ}.$
• Key concept: many biological processes rely on coupling a nonspontaneous step to a spontaneous step to achieve a favorable overall ΔG.
• Entropy and order: living systems maintain order (low entropy locally) by continuously exchanging energy with their environment; this is not violation of the second law, since the total entropy of the universe still increases.
• The idea of organized systems emerging from disordered states is allowed when energy input maintains order and permits, paradoxically, highly organized structures to exist.
• Equilibria in chemistry vs biology:
  • Chemical systems often proceed toward passive equilibrium (no ongoing energy input).
  • Biological systems maintain active equilibria by continuously consuming energy to sustain order and function.
• Dynamos of equilibrium exemplified:
  • Passive equilibrium: a pond (close to equilibrium, bulk water remains in a relatively static state).
  • Active equilibrium: an air conditioner maintains a stable temperature by ongoing energy input; a vending machine stocked with sandwiches that are not replenished is an example of passive stability in economic terms, but an actively run establishment (like Subway) maintains order through ongoing energy input and service.
• Consequences for biology: living systems must remain in an active steady state, constantly using energy to maintain order against natural dispersion; death leads to passive equilibrium and decay.

Connecting thermodynamics to biology: hydrophobic effect and noncovalent interactions (preview)

• The hydrophobic effect and noncovalent interactions (hydrogen bonding, van der Waals forces, ionic interactions) are central to biomolecular structure and function.
• Expect upcoming topics to tie entropy, enthalpy, and free energy to how biomolecules fold, assemble, and interact in aqueous environments.

Practical takeaways and study tips

• Rehearse general chemistry fundamentals, especially acids/bases, kinetics, molecular shapes, and polarity.
• Review organic chemistry functional groups and mechanisms; be able to recognize functional groups by sight and relate structure to behavior in biomolecules.
• Learn and memorize key biomolecule classes and their monomer units, typical polymers, and their general roles in metabolism, information storage, energy, and structure.
• Understand the concept of residues and why the overall polymer structure matters more than every single atom in large biomolecules.
• Practice the central dogma steps and their implications for how information flows from DNA to functional proteins.
• Develop fluency with thermodynamics language: ΔG, ΔH, ΔS, and when coupled reactions lead to spontaneity.
• Be able to explain why lipids form membranes and how amphiphilicity drives bilayer organization.
• Use analogies to grasp active vs passive equilibria and why living systems require constant energy input to maintain order.
• Look ahead to hydrophobic effects and noncovalent interactions for deeper understanding of protein folding and membrane dynamics.

Quick reference equations and terms

• Gibbs free energy: $riangle G = riangle H - T riangle S$
• Spontaneous condition: riangle G < 0
• Nonspontaneous condition: riangle G > 0
• Central dogma steps: Replication, Transcription, Translation
• Lipid bilayer architecture: amphiphilic molecules with hydrophilic heads and hydrophobic tails; bilayer core is nonpolar
• Key biomolecule classes: proteins, nucleic acids, carbohydrates, lipids
• Polymer vs. monomer: polymers formed from monomeric units; residues are monomer units in biopolymers
• Functional groups to recognize: amine, alcohol (hydroxyl), thiol, ether, aldehyde, ketone, carboxylic acid, carboxylate, ester, amide, imine, phosphoester, diphosphate ester