1.2 The Chemical Foundations · 2027 Biochemistry

Biomolecules are carbon compounds carrying functional groups

Four covalent bonds — carbon forms chain, branched and ring skeletons; single and double bonds create further variety
Rotation — C–C single bonds rotate; double bonds are restricted by the π bond, shaping flexibility, planarity and accessibility
Functional groups — hydroxyl, carbonyl, carboxyl, amino, sulfhydryl, phosphate, methyl and amide groups set polarity, charge and reactivity
Several groups at once — glycine carries amino and carboxyl; glucose carries hydroxyls and a carbonyl and is mainly cyclic in solution
Zwitterions — in biological solutions amino acids usually carry both NH₃⁺ and COO⁻
pH dependence — above its pKa a carboxyl group is deprotonated; an amino group loses its proton as pH rises

pH = pKa + log([A⁻]/[HA])

Figure 1-2-1Common functional groups and their properties

Table 1.2-1Common functional groups and their properties

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Biomolecules are carbon compounds carrying functional groups

Four covalent bonds — carbon forms chain, branched and ring skeletons; single and double bonds create further variety
Rotation — C–C single bonds rotate; double bonds are restricted by the π bond, shaping flexibility, planarity and accessibility
Functional groups — hydroxyl, carbonyl, carboxyl, amino, sulfhydryl, phosphate, methyl and amide groups set polarity, charge and reactivity
Several groups at once — glycine carries amino and carboxyl; glucose carries hydroxyls and a carbonyl and is mainly cyclic in solution
Zwitterions — in biological solutions amino acids usually carry both NH₃⁺ and COO⁻
pH dependence — above its pKa a carboxyl group is deprotonated; an amino group loses its proton as pH rises

pH = pKa + log([A⁻]/[HA])

Figure 1-2-1Common functional groups and their properties

Cells contain a common set of small molecules

Monosaccharides and sugar phosphates — carbon and energy supply, nucleic acid precursors
Amino acids — protein synthesis and nitrogen metabolism
Nucleotides — nucleic acid synthesis, phosphate transfer, signalling
Organic acids and intermediates — linking carbon skeletons between pathways
Fatty acids and lipid precursors — membrane and storage lipids
Cofactors and coenzymes — NAD⁺/NADH, FAD, coenzyme A carrying electrons and groups
Inorganic ions — Mg²⁺, K⁺, Ca²⁺, Fe²⁺/Fe³⁺ for charge balance, catalysis, signalling and electron transfer

Figure 1-2-2Small molecules and inorganic components cells share

Table 1.2-2Small molecules and inorganic components that cells share

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Cells contain a common set of small molecules

Monosaccharides and sugar phosphates — carbon and energy supply, nucleic acid precursors
Amino acids — protein synthesis and nitrogen metabolism
Nucleotides — nucleic acid synthesis, phosphate transfer, signalling
Organic acids and intermediates — linking carbon skeletons between pathways
Fatty acids and lipid precursors — membrane and storage lipids
Cofactors and coenzymes — NAD⁺/NADH, FAD, coenzyme A carrying electrons and groups
Inorganic ions — Mg²⁺, K⁺, Ca²⁺, Fe²⁺/Fe³⁺ for charge balance, catalysis, signalling and electron transfer

Figure 1-2-2Small molecules and inorganic components cells share

[Separate note] Molecular mass and its units

Molecular mass — the mass of one molecule, in kg or Da
Relative molecular mass (Mr) — the ratio to the atomic mass unit; dimensionless
Molar mass — mass divided by amount of substance, g/mol
Dalton — 1 Da = 1 u = 1/12 the mass of a ¹²C atom
Example A — glucose C₆H₁₂O₆ gives Mr = 180.156, so one molecule ≈ 180.156 Da and one mole ≈ 180.156 g
Example B — a 50 kDa protein has a molar mass of 50,000 g/mol; 0.10 μmol weighs 5.0 mg
Example C — Gly-Gly: 2 × 75.07 − 18.015 = 132.125 g/mol; n residues form n−1 bonds

Mr(C₆H₁₂O₆) = 6(12.01) + 12(1.008) + 6(16.00) = 180.156

Figure 1-2-3Representative masses of molecules and complexes

Table 1.2-4Biomolecule classes: building units, linkages and structural features

Table 1.2-3Molecular mass, relative molecular mass and molar mass

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[Separate note] Molecular mass and its units

Molecular mass — the mass of one molecule, in kg or Da
Relative molecular mass (Mr) — the ratio to the atomic mass unit; dimensionless
Molar mass — mass divided by amount of substance, g/mol
Dalton — 1 Da = 1 u = 1/12 the mass of a ¹²C atom
Example A — glucose C₆H₁₂O₆ gives Mr = 180.156, so one molecule ≈ 180.156 Da and one mole ≈ 180.156 g
Example B — a 50 kDa protein has a molar mass of 50,000 g/mol; 0.10 μmol weighs 5.0 mg
Example C — Gly-Gly: 2 × 75.07 − 18.015 = 132.125 g/mol; n residues form n−1 bonds

Mr(C₆H₁₂O₆) = 6(12.01) + 12(1.008) + 6(16.00) = 180.156

Figure 1-2-3Representative masses of molecules and complexes

Macromolecules are the main components of cells

Proteins — amino acids joined by peptide (amide) bonds; N-terminal to C-terminal sequence
Polysaccharides — monosaccharides joined by glycosidic bonds; α/β linkage and branching change the material
Nucleic acids — nucleotides joined by 3′–5′ phosphodiester bonds with 5′→3′ directionality
Lipids — phospholipids, triglycerides and steroids differ too much for one repeating monomer
Condensation and hydrolysis — the overall stoichiometry; real synthesis needs activated precursors, tRNA and ribosomes
Beyond the sum of parts — sequence constrains folding, base complementarity stores information, branching separates starch, glycogen and cellulose
Levels of protein structure — primary, secondary, tertiary and quaternary; flexible and disordered regions exist

Figure 1-2-4Biomolecule classes: units, linkages, features

Three-dimensional structure: configuration and conformation

Configuration — spatial difference not removed by rotation about a single bond: enantiomers, E/Z isomers
Conformation — arrangement changed by rotation about single bonds or by folding
Chirality — not superimposable on its mirror image; a carbon with four different substituents is a chiral centre, but not every chiral molecule has one
Enantiomers — identical in achiral environments, opposite in optical rotation and different in chiral recognition
D/L, R/S, (+)/(−) — relative configuration, absolute configuration by CIP priority, and observed rotation are three different systems
Conformational energy — eclipsed and staggered arrangements differ; rotation is possible but not free of energy cost

ΔG for rotation: staggered is favoured over eclipsed

Figure 1-2-5Connectivity, configuration and conformation

Figure 1-2-6Fischer projections of D- and L-glyceraldehyde

[Separate note] Pasteur and optical activity

Observation — tartrate crystals of identical composition differed in optical activity
Classification — two mirror-image crystal forms were identified in paratartrate samples
Separation and measurement — individual crystals were picked apart and each solution rotated polarised light in the opposite direction
Interpretation — equal amounts of both enantiomers cancel, leaving no apparent activity
Measurement — α = [α]_λ,T · l · c; sucrose [α]_D,20 ≈ +66.5°·mL·g⁻¹·dm⁻¹, so 10 % (w/v) in a 10 cm cell gives about +6.65°
Legacy — the basis of enzyme stereospecificity, biomolecular chirality and enantiomeric drugs
Caution — zero rotation does not prove achirality: a racemic mixture also reads zero

α = [α]_λ,T · l · c

Figure 1-2-7Pasteur’s separation of mirror-image crystals

Figure 1-2-8Polarimetry: principle of the measurement

Reactions between biomolecules can be stereospecific

Chiral active site — proteins built from L-amino acids create a chiral pocket, so enantiomers make different contacts
Stereospecific — a difference in substrate configuration leads to a different outcome or pathway
Stereoselective — one of several possible stereoisomeric products predominates
Beyond lock and key — induced fit and selection among pre-existing conformations; substrate orientation changes the activation barrier
Chiral choices of life — proteins use L-α-amino acids, nucleic acids use D-sugars, yet D-amino acids occur in some bacterial cell walls

Figure 1-2-9A simple model of stereospecific substrate recognition

Key concepts

Carbon and functional groups — the skeleton sets shape; the groups set reactivity, charge and solubility
Groups and pH — protonation follows pKa and the surrounding environment
Small molecules — sugars, amino acids, nucleotides and cofactors feed connected reactions
Mass units — Da, g/mol and a dimensionless Mr are not interchangeable
Macromolecule classes — proteins, polysaccharides and nucleic acids are polymers; lipids are not uniformly so
Configuration and conformation — two different descriptions of spatial structure
Chirality — recognition differs in chiral environments

Figure 1-2-10Key relationships between the chemical foundations

References

**Table 1.2-1**Common functional groups and their properties
Functional group	Typical molecules and positions	Biochemical significance
Hydroxyl (–OH)	Sugars, glycerol, serine	Increases polarity and hydrogen bonding
Carbonyl (>C=O)	Aldehyde and ketone forms of sugars	Can be a target of nucleophilic attack
Carboxyl (–COOH / –COO⁻)	Fatty acids, amino acids	Involved in acid–base reactions, charge and ionic bonding
Amino (–NH₂ / –NH₃⁺)	Amino acids, many metabolites	Proton acceptance and electrostatic attraction
Sulfhydryl (–SH)	Cysteine, coenzyme A	Important in redox reactions and disulfide bonds
Phosphate (phosphate ester etc.)	ATP, nucleic acids, sugar phosphates	Phosphate transfer, negative charge, enzyme recognition
Methyl (–CH₃)	Fatty acids, DNA methylation sites	Hydrophobicity and some recognition and regulation
Amide (–CONH–)	Peptide bonds in proteins	Bond character from resonance and hydrogen bonding

**Table 1.2-2**Small molecules and inorganic components that cells share
Class	Examples	Main functions
Monosaccharides and sugar phosphates	Glucose, ribose, glucose 6-phosphate	Carbon supply, energy metabolism, nucleic acid components
Amino acids	Glycine, alanine, glutamate	Protein synthesis and nitrogen metabolism
Nucleotides	ATP, GTP, CTP, UTP, dATP	Nucleic acid synthesis, phosphate transfer, signalling
Organic acids and intermediates	Pyruvate, lactate, citrate	Link carbon skeletons between pathways
Fatty acids and lipid precursors	Palmitate, glycerol 3-phosphate	Formation of membrane and storage lipids
Cofactors and coenzymes	NAD⁺/NADH, FAD, coenzyme A	Electron and group carriers; assistance of enzyme reactions
Inorganic ions	Mg²⁺, K⁺, Ca²⁺, Fe²⁺/Fe³⁺	Charge balance, catalysis, signalling, electron transfer

**Table 1.2-3**Molecular mass, relative molecular mass and molar mass
Term	Definition	Unit and example
Molecular mass	Mass of one molecule	kg or Da; water ≈ 18.015 Da
Relative molecular mass (Mr)	Mass of one molecule divided by the atomic mass unit u	Dimensionless; Mr of water ≈ 18.015
Molar mass (M)	Mass divided by amount of substance	g/mol or kg/mol; water ≈ 18.015 g/mol
Dalton (Da)	1 Da = 1 u = 1/12 the mass of a ¹²C atom	1 Da ≈ 1.66054×10⁻²⁷ kg
Molecular weight	Customary term used for relative molecular mass and others	Meaning varies with context; a precise name is preferred

**Table 1.2-4**Biomolecule classes: building units, linkages and structural features
Class	Building unit	Typical linkage	Structural features
Proteins	Amino acids	Peptide (amide) bond	N-terminal to C-terminal sequence; diverse side chains
Polysaccharides	Monosaccharides	Glycosidic bond	Properties change with α/β linkage and branching
DNA and RNA	Nucleotides	3′–5′ phosphodiester bond	5′→3′ directionality; sequence stores information
Lipids	Fatty acids, glycerol, phosphate (varies)	Ester, amide and others (varies)	Hydrophobic or amphipathic; bilayers or storage

**Figure 1-2-1**Common functional groups and their properties

**Figure 1-2-2**Small molecules and inorganic components cells share

**Figure 1-2-3**Representative masses of molecules and complexes

**Figure 1-2-4**Biomolecule classes: units, linkages, features

**Figure 1-2-5**Connectivity, configuration and conformation

**Figure 1-2-6**Fischer projections of D- and L-glyceraldehyde

**Figure 1-2-7**Pasteur’s separation of mirror-image crystals

**Figure 1-2-8**Polarimetry: principle of the measurement

**Figure 1-2-9**A simple model of stereospecific substrate recognition

**Figure 1-2-10**Key relationships between the chemical foundations