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

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

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

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

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

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Reference tables

Data tables for this section, shown on click and printed in the appendix.