1.1 The Cellular Foundation · 2027 Biochemistry

The cell is the structural and functional unit of life

Biochemistry — explains, at the molecular level, how biomolecules obeying ordinary chemical and physical laws interact to produce the properties of life
Six properties of living organisms — chemical complexity and organisation, energy extraction and conversion, precise regulation, sensing and response, self-replication and self-assembly, gradual evolution
Plasma membrane — a selectively permeable fluid mosaic of phospholipid bilayer with transport, receptor and signalling proteins; maintains membrane potential
Cytoplasm ⊃ cytosol — cytoplasm is everything inside the membrane; cytosol is the gel-like, crowded aqueous phase excluding the nucleus or nucleoid, where glycolysis, the pentose phosphate pathway, fatty acid synthesis and protein synthesis occur
Genome — every cell carries DNA for at least part of its cycle: a membrane-free nucleoid in prokaryotes, a double-membrane nucleus with linear chromosomes in eukaryotes

Figure 1-1-1Universal architecture shared by every cell: membrane, cytoplasm and genome

Table 1.1-1Universal components of a cell and their biochemical roles

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The cell is the structural and functional unit of life

Biochemistry — explains, at the molecular level, how biomolecules obeying ordinary chemical and physical laws interact to produce the properties of life
Six properties of living organisms — chemical complexity and organisation, energy extraction and conversion, precise regulation, sensing and response, self-replication and self-assembly, gradual evolution
Plasma membrane — a selectively permeable fluid mosaic of phospholipid bilayer with transport, receptor and signalling proteins; maintains membrane potential
Cytoplasm ⊃ cytosol — cytoplasm is everything inside the membrane; cytosol is the gel-like, crowded aqueous phase excluding the nucleus or nucleoid, where glycolysis, the pentose phosphate pathway, fatty acid synthesis and protein synthesis occur
Genome — every cell carries DNA for at least part of its cycle: a membrane-free nucleoid in prokaryotes, a double-membrane nucleus with linear chromosomes in eukaryotes

Figure 1-1-1Universal architecture shared by every cell: membrane, cytoplasm and genome

Cell size is constrained by diffusion

Lower bound — independent metabolism and reproduction need space for a genome, hundreds of enzymes, ribosomes, tRNA and membrane components; Mycoplasma at 0.1–0.2 μm is close to the theoretical minimum
Upper bound — metabolic demand scales with volume while exchange scales with surface area; most animal and plant cells are 5–100 μm across
Scaling — S = 4πr², V = (4/3)πr³, so S/V = 3/r; a 10× larger radius gives 100× the surface but 1,000× the volume
Diffusion time — t = x²/(6D): a 10× longer path costs 100× the time
Consequence — beyond a certain size the cell core cannot be supplied fast enough and reaches metabolic suffocation
Four strategies — maximise surface (microvilli), change shape (neurons, muscle fibres), re-partition space (central vacuole), and active transport (cytoplasmic streaming, vesicle traffic)

S/V = 3/r · t = x²/(6D)

Figure 1-1-2Surface-to-volume ratio and diffusion time as cell size increases

Table 1.1-2Surface area, volume and A/V ratio of spherical cells

Table 1.1-5Major components of a typical animal cell

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Cell size is constrained by diffusion

Lower bound — independent metabolism and reproduction need space for a genome, hundreds of enzymes, ribosomes, tRNA and membrane components; Mycoplasma at 0.1–0.2 μm is close to the theoretical minimum
Upper bound — metabolic demand scales with volume while exchange scales with surface area; most animal and plant cells are 5–100 μm across
Scaling — S = 4πr², V = (4/3)πr³, so S/V = 3/r; a 10× larger radius gives 100× the surface but 1,000× the volume
Diffusion time — t = x²/(6D): a 10× longer path costs 100× the time
Consequence — beyond a certain size the cell core cannot be supplied fast enough and reaches metabolic suffocation
Four strategies — maximise surface (microvilli), change shape (neurons, muscle fibres), re-partition space (central vacuole), and active transport (cytoplasmic streaming, vesicle traffic)

S/V = 3/r · t = x²/(6D)

Figure 1-1-2Surface-to-volume ratio and diffusion time as cell size increases

Life is divided into three domains

Old view — prokaryotes versus eukaryotes, judged by the nuclear envelope
Turning point — Woese and colleagues compared 16S and 18S rRNA sequences in the late 1970s
Molecular clock — rRNA genes occur in every organism and are highly conserved, making them a reliable measure of evolutionary distance
Three domains — Bacteria, Archaea, Eukarya; the former "prokaryotes" are two lineages that diverged at the base of the tree
LUCA — all three domains descend from a last universal common ancestor roughly 3.5–3.8 billion years ago; Archaea are closer to Eukarya than to Bacteria
Dual genetic origin — information-processing genes come from the archaeal line, operational metabolism from the bacterial line

Figure 1-1-3The three domains and the position of eukaryotes

Table 1.1-3The three domains of life

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Life is divided into three domains

Old view — prokaryotes versus eukaryotes, judged by the nuclear envelope
Turning point — Woese and colleagues compared 16S and 18S rRNA sequences in the late 1970s
Molecular clock — rRNA genes occur in every organism and are highly conserved, making them a reliable measure of evolutionary distance
Three domains — Bacteria, Archaea, Eukarya; the former "prokaryotes" are two lineages that diverged at the base of the tree
LUCA — all three domains descend from a last universal common ancestor roughly 3.5–3.8 billion years ago; Archaea are closer to Eukarya than to Bacteria
Dual genetic origin — information-processing genes come from the archaeal line, operational metabolism from the bacterial line

Figure 1-1-3The three domains and the position of eukaryotes

Organisms obtain energy and biosynthetic precursors from different sources

Energy axis — phototrophs use light; chemotrophs use chemical energy from oxidation–reduction reactions
Carbon axis — autotrophs reduce CO₂; heterotrophs use preformed organic compounds
Photoautotrophs — plants, algae, cyanobacteria; oxygenic when water is the electron donor, anoxygenic with H₂S, S⁰ or H₂
Photoheterotrophs — purple and green nonsulfur bacteria, some halophilic archaea using bacteriorhodopsin
Chemoautotrophs — sulfur-oxidising, nitrifying and hydrogen bacteria; methanogenic archaea at deep-sea vents
Chemoheterotrophs — all animals, all fungi, most protists and many bacteria

Figure 1-1-4The four trophic groups arranged by energy and carbon source

Table 1.1-7Experimental groups for testing enzyme activity

Bacteria and archaea share a plan but differ crucially

Shared — no nuclear envelope, 0.5–5 μm, a single circular chromosome, 70S ribosomes, plasmids, flagella and pili
Bacterial wall — peptidoglycan of alternating NAG and NAM cross-linked by peptides; thick in Gram-positive, thin with an outer membrane in Gram-negative
Difference 1 — no peptidoglycan in archaea: pseudopeptidoglycan or a crystalline S-layer, so penicillin and lysozyme do not act
Difference 2 — ether lipids: D-glycerol, branched isoprenoids and ether linkages instead of ester bonds; GDGT monolayers survive boiling water and strong acid
Difference 3 — information machinery closer to eukaryotes: RNA polymerase, transcription factors and translation initiation proteins

Figure 1-1-5Biochemical comparison of Bacteria, Archaea and Eukarya

Table 1.1-4Membrane lipids and cell walls: bacteria versus archaea

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Bacteria and archaea share a plan but differ crucially

Shared — no nuclear envelope, 0.5–5 μm, a single circular chromosome, 70S ribosomes, plasmids, flagella and pili
Bacterial wall — peptidoglycan of alternating NAG and NAM cross-linked by peptides; thick in Gram-positive, thin with an outer membrane in Gram-negative
Difference 1 — no peptidoglycan in archaea: pseudopeptidoglycan or a crystalline S-layer, so penicillin and lysozyme do not act
Difference 2 — ether lipids: D-glycerol, branched isoprenoids and ether linkages instead of ester bonds; GDGT monolayers survive boiling water and strong acid
Difference 3 — information machinery closer to eukaryotes: RNA polymerase, transcription factors and translation initiation proteins

Figure 1-1-5Biochemical comparison of Bacteria, Archaea and Eukarya

Membranous organelles separate reactions in space

Scale — eukaryotic cells are 10–100 μm, roughly 10× the linear dimension and 1,000–10,000× the volume of a prokaryote
Three benefits — isolate opposing pathways, concentrate enzymes and substrates, and confine hazardous chemistry away from the cytosol
Nucleus and nucleolus — double membrane with pores; replication and transcription, plus rRNA synthesis and ribosome assembly
Mitochondria and chloroplasts — double-membrane energy converters; their own circular DNA, 70S ribosomes and division by fission support the endosymbiotic origin
ER and Golgi — folding, disulfide bonding and N-glycosylation in the rough ER; lipid and steroid synthesis, detoxification and Ca²⁺ storage in the smooth ER; glycan maturation and sorting in the Golgi
Lysosomes, peroxisomes, vacuoles — acid hydrolases at pH 4.5–5.0; catalase destroying H₂O₂; turgor and storage

Figure 1-1-6Organelles of a eukaryotic cell and their functions

The cytoskeleton makes structure and transport dynamic

Functions — mechanical strength, organelle anchoring, chromosome and cytoplasm partitioning, cell movement
Actin microfilaments — 6–7 nm, ATP-binding G-actin, polar; cortex, microvilli, muscle contraction, contractile ring; motor: myosin
Microtubules — 25 nm hollow tubes of α/β-tubulin, GTP-binding, dynamic instability; transport tracks, spindle, axoneme; motors: kinesin and dynein
Intermediate filaments — 8–12 nm, coiled-coil tetramers, no polarity, most stable; resist tension, support the lamina, anchor desmosomes
Dynamics — treadmilling and dynamic instability reorganise the whole skeleton within seconds to minutes

Figure 1-1-7The three cytoskeletal fibres compared

Table 1.1-6The three cytoskeletal elements

The cell functions as a supramolecular organisation

Level 1 — monomeric subunits: nucleotides, amino acids, monosaccharides, fatty acids, 100–300 Da
Level 2 — macromolecules joined by covalent bonds: DNA, RNA, polypeptides, polysaccharides, 10⁴–10⁹ Da
Level 3 — supramolecular complexes: ribosomes, chromatin, proteasomes, pyruvate dehydrogenase complex, membranes, cytoskeletal fibres
Level 4 — organelles and the cell, 1–100 μm
Bonding switch — covalent at 1→2, noncovalent at 2→3: hydrogen bonds, ionic interactions, hydrophobic effect, van der Waals contacts
Core principle — individually weak bonds acting cooperatively hold complexes together while allowing rapid, low-energy assembly and disassembly

NOTEC–C ≈ 350 kJ/mol · noncovalent 0.4–30 kJ/mol

Figure 1-1-8Levels of supramolecular organisation in the cell

In vitro experiments test interactions between biomolecules

In vitro — lyse cells, purify the molecule of interest, measure catalysis and binding under controlled temperature, pH and ionic strength
Limitation — protein at 0.1–1 mg/mL occupies well under 0.1 % of the volume: an extremely dilute world
In vivo — protein and RNA at 200–300 mg/mL occupy 20–30 % of the cytosolic volume
Excluded volume — crowding raises effective concentration several-fold above the actual molarity
Folding and assembly — the drive to minimise excluded volume favours compact folds and multienzyme complexes
Slower diffusion — large proteins diffuse 5–10× more slowly, favouring substrate channelling along adjacent enzymes

NOTEDilute in vitro solution compared with the crowded in vivo cytosol

Figure 1-1-9Dilute in vitro solution compared with the crowded in vivo cytosol

Key concepts

Universality — membrane, cytoplasm and genome define a cell
Size limit — S/V ratio and diffusion time bound cell dimensions; four strategies extend them
Three domains — Bacteria, Archaea, Eukarya, with eukaryotes closest to the archaeal line
Four trophic groups — the two axes of energy and carbon source
Prokaryotic divide — peptidoglycan, ether lipids and information machinery separate bacteria from archaea
Compartmentation — membranous organelles buy isolation, concentration and protection
Supramolecular order — weak cooperative bonds give both stability and reversibility

Figure 1-1-10Summary diagram of the cellular foundations

References

**Table 1.1-1**Universal components of a cell and their biochemical roles
Component	Main chemical composition	Biochemical significance
Cell membrane	Mainly lipids and membrane proteins	Defines inside and outside; regulates transport and signalling
Cytoplasm	Water, ions, metabolites, proteins	The space for metabolism and complex molecular interaction
Genetic material	DNA, the cell's hereditary information	Stores the information needed to synthesise enzymes and structural proteins
Ribosome	rRNA–protein complex	Reads mRNA and synthesises protein

**Table 1.1-2**Surface area, volume and A/V ratio of spherical cells
Radius r (μm)	Surface area A (μm²)	Volume V (μm³)	A/V (μm⁻¹)
1	≈12.57	≈4.19	3.00
2	≈50.27	≈33.51	1.50
4	≈201.06	≈268.08	0.75

**Table 1.1-3**The three domains of life
Domain	Nuclear envelope	Representative organisms	Biochemically important features
Bacteria	Absent	E. coli, cyanobacteria	Cell wall often contains peptidoglycan
Archaea	Absent	Methanogenic archaea and others	Membrane lipid chemistry and information machinery differ from bacteria
Eukarya	Present	Animals, plants, fungi, protists	Nucleus and membranous organelles divide the labour

**Table 1.1-4**Membrane lipids and cell walls: bacteria versus archaea
Feature	Bacteria	Archaea
Shared cellular features	No nuclear envelope; DNA, ribosomes and a plasma membrane	No nuclear envelope; DNA, ribosomes and a plasma membrane
Typical membrane lipid linkage	Fatty acid–glycerol ester bond	Isoprenoid–glycerol ether bond
Cell wall	Many species have peptidoglycan	No peptidoglycan; protein layers and other types
Transcription machinery	Relatively simple RNA polymerase system	Several components resemble those of eukaryotes
Habitat	Very broad	Very broad, including extreme environments

**Table 1.1-5**Major components of a typical animal cell
Structure	Main function	Biochemical link
Nucleus	DNA storage and replication, RNA transcription	Genetic information is passed to mRNA
Rough ER	Synthesis and early processing of secretory and membrane proteins	Ribosome translation is coupled to protein folding
Smooth ER	Lipid synthesis, Ca²⁺ storage, some detoxification	Contributes membrane components and signal control
Golgi apparatus	Modification, sorting and transport of protein and lipid	Glycan modification and vesicle traffic
Mitochondrion	Aerobic energy metabolism, many intermediates	Inner-membrane electron transport and ATP synthase
Lysosome	Breakdown and recycling of macromolecules	Acid hydrolases act at low pH
Peroxisome	Oxidation of certain fatty acids, H₂O₂ metabolism	Catalase and related enzymes
Chloroplast (plants)	Photosynthesis and carbon fixation	Photochemistry on the thylakoid membrane

**Table 1.1-6**The three cytoskeletal elements
Element	Main protein and features	Representative functions
Microfilament	Actin; about 7 nm	Cell movement, cytokinesis, muscle contraction
Intermediate filament	Keratin and others; about 10 nm	Mechanical stability; maintenance of nuclear and cell shape
Microtubule	α/β-tubulin; outer diameter about 25 nm	Vesicle and organelle transport, cilia and flagella, mitotic spindle

**Table 1.1-7**Experimental groups for testing enzyme activity
Group	Enzyme	Substrate	Purpose
A	Active catalase	Present	Baseline for the normal reaction
B	None	Present	No-enzyme control
C	Heat-treated catalase	Present	Tests the link between structure and activity
D	Active catalase	Absent	Tests whether substrate is required

**Figure 1-1-1**Universal architecture shared by every cell: membrane, cytoplasm and genome

**Figure 1-1-2**Surface-to-volume ratio and diffusion time as cell size increases

**Figure 1-1-3**The three domains and the position of eukaryotes

**Figure 1-1-4**The four trophic groups arranged by energy and carbon source

**Figure 1-1-5**Biochemical comparison of Bacteria, Archaea and Eukarya

**Figure 1-1-6**Organelles of a eukaryotic cell and their functions

**Figure 1-1-7**The three cytoskeletal fibres compared

**Figure 1-1-8**Levels of supramolecular organisation in the cell

**Figure 1-1-9**Dilute in vitro solution compared with the crowded in vivo cytosol

**Figure 1-1-10**Summary diagram of the cellular foundations