IMAT Biology · Biomolecules and Enzymes

Amino Acids, Protein Structure and Nucleotides

Proteins are chains of amino acids joined by peptide bonds and folded through four levels of structure; nucleic acids are chains of nucleotides joined by phosphodiester bonds.

All Biomolecules and Enzymes notes

Why this matters

This is the most asked part of the chapter. The older papers asked about the parts of an amino acid (2015, 2020), the bond that breaks in a dipeptide (2016), the levels of structure of haemoglobin and of an enzyme (2017, 2018) and which structures contain proteins (2013, 2018). The 2025 ministry paper asked where collagen is found.

Concept 1 of 5: The structure of an amino acid

All amino acids share the same backbone: a central carbon holding an amino group, a carboxyl group and a hydrogen atom. The fourth position holds the R group, and that is the only part that changes. Twenty different R groups give twenty amino acids, and their different sizes, charges and polarities are what make each protein fold its own way.

Definition

An amino acid has a central carbon (the α-carbon) bonded to an amino group $\mathrm{-NH_2}$ , a carboxyl group $\mathrm{-COOH}$ , a hydrogen atom and a variable R group (side chain).
The part common to every amino acid is the α-carbon with its amino group, carboxyl group and H. Only the R group differs.
The carboxyl group is the acidic group (it can lose $\mathrm{H^+}$ ); the amino group is basic (it can gain $\mathrm{H^+}$ ). At the pH of the body an amino acid carries both charges at once (a zwitterion).
There are 20 amino acids in human proteins. Essential amino acids (nine in adults) cannot be made by the body and must come from food.
Glycine has the simplest R group, a single H atom. Cysteine and methionine contain sulfur.

Part	Formula	Property
Amino group	$\mathrm{-NH_2}$	Basic; same in all amino acids
Carboxyl group	$\mathrm{-COOH}$	Acidic; same in all amino acids
Hydrogen on the α-carbon	$\mathrm{-H}$	Same in all amino acids
R group (side chain)	Varies (H in glycine, $\mathrm{CH_3}$ in alanine)	Decides polarity, charge and size; the only part that differs

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The R group can contain N, O or even its own COOH

Some R groups carry extra amino, amide or carboxyl groups. When asked for the part common to all amino acids, choose the α-carbon with one amino group, one carboxyl group and one H, and treat everything else on that carbon as the R group.

Concept 2 of 5: The peptide bond and the mass of a polypeptide

The carboxyl group of one amino acid reacts with the amino group of the next. An OH and an H leave as water, and the carbon of the first is joined directly to the nitrogen of the second. Repeat this and you get a chain with a free amino group at one end and a free carboxyl group at the other.

Definition

A peptide bond is the C-N bond between the carbon of one amino acid's carboxyl group and the nitrogen of the next amino acid's amino group: $\mathrm{-CO-NH-}$ .
It forms by condensation (one water released) on the ribosome, and is broken by hydrolysis, which splits exactly this C-N bond.
Two amino acids make a dipeptide, many make a polypeptide. A chain has an N-terminus (free amino group) and a C-terminus (free carboxyl group).
One chain of $n$ amino acids has $n-1$ peptide bonds. A protein of $k$ separate chains with $n$ amino acids in total has $n-k$ .
Proteases (peptidases) are the enzymes that hydrolyse peptide bonds.

Mass of a single polypeptide chain

M = n\,\bar{m} - 18\,(n-1)

$n$ number of amino acids in the chain
$\bar{m}$ average relative mass of the free amino acids
$18$ relative mass of one water molecule lost per peptide bond

Worked example

Glycine

(\mathrm{C_2H_5NO_2}

, relative mass 75) joins alanine

(\mathrm{C_3H_7NO_2}

, relative mass 89) by a peptide bond. Give the formula and relative mass of the dipeptide.

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Hydrolysis breaks the C-N peptide bond, not a bond inside an R group

To split a dipeptide back into its two amino acids, the bond between the carbonyl carbon and the nitrogen of the next unit is broken by adding water. The C=O and N-H bonds next to it, and bonds in the R groups, stay as they are.

Concept 3 of 5: The four levels of protein structure

The amino acid sequence is like a string of beads. Hydrogen bonds along the backbone twist parts of the string into coils and pleats. Attractions between the R groups then fold the whole chain into one particular 3D shape. Some proteins also need several folded chains fitted together before they work.

Definition

Primary structure: the sequence of amino acids, held by peptide bonds. It is coded by the gene and decides every higher level.
Secondary structure: the α-helix and the β-pleated sheet, held by hydrogen bonds between the C=O and N-H groups of the backbone.
Tertiary structure: the overall 3D folding of one chain, held by interactions between R groups: hydrogen bonds, ionic bonds, disulfide bridges (covalent S-S bonds between two cysteines) and hydrophobic interactions.
Quaternary structure: two or more polypeptide chains held together, sometimes with a non-protein prosthetic group. Only proteins with more than one chain have it.
The shape of an enzyme's active site depends on every level the protein has. If the active site is built from two chains, the quaternary level shapes it too.

Level	What it is	Held by	Example
Primary	Sequence of amino acids	Peptide bonds	Any protein; one change can alter the whole fold (sickle cell haemoglobin)
Secondary	α-helix or β-pleated sheet	Hydrogen bonds in the backbone	α-helices of keratin; β-sheets of silk
Tertiary	3D fold of a single chain	R-group bonds: hydrogen, ionic, disulfide, hydrophobic	Myoglobin (one chain); many enzymes
Quaternary	Several chains together	The same R-group bonds, between chains	Haemoglobin (four chains, each with a haem group); collagen (three chains)

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A protein with a quaternary level still has all the lower levels

Levels build on each other. A protein made of several chains has primary, secondary, tertiary and quaternary structure, never a quaternary structure with a level missing. A single-chain protein stops at tertiary.

Concept 4 of 5: Fibrous and globular proteins, where they act, and denaturation

Long fibrous proteins are built to be strong and insoluble, like ropes and cables. Globular proteins are compact and soluble, built to carry, signal and catalyse. Both depend on their shape, and that shape is held mostly by weak bonds. Heat or the wrong pH breaks those weak bonds and the protein unfolds.

Definition

Fibrous proteins (collagen, keratin, elastin) are long, insoluble and structural.
Globular proteins (enzymes, haemoglobin, antibodies, insulin) are compact, soluble and do metabolic jobs.
Collagen is the most abundant protein in mammals. It is secreted by cells and works outside them, in the extracellular matrix of skin, tendons, bone and cartilage.
Proteins are part of membranes (channels and carriers), ribosomes (rRNA plus protein), cilia (microtubules of tubulin), viruses (the capsid), antibodies and enzymes. Amylose, triglycerides and cholesterol contain no protein.
Denaturation: heat, extreme pH, heavy-metal ions or some solvents break the hydrogen bonds, ionic bonds and hydrophobic interactions that hold the 3D shape. The protein unfolds and loses its function. The peptide bonds stay intact, so the primary structure is unchanged. It is usually irreversible.
The biuret test (turns purple) detects peptide bonds.

Protein	Type	Where it acts	Function
Collagen	Fibrous	Outside cells (extracellular matrix)	Tensile strength of skin, tendon, bone
Keratin	Fibrous	Inside cells of skin, hair and nails	Toughness, waterproofing
Haemoglobin	Globular	Inside red blood cells	Carries oxygen
Antibodies	Globular	Blood plasma and body fluids	Bind antigens
Myosin and actin	Fibrous filaments	Inside muscle cells	Contraction (myosin thick filaments, actin thin filaments)

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Denaturation does not break peptide bonds

A denatured protein has lost its shape, not its sequence. Breaking peptide bonds is hydrolysis, done by proteases or by boiling in strong acid for a long time, not by ordinary heating.

Collagen is not a muscle filament

Collagen is a fibrous protein outside cells, in connective tissue. The thick filaments in muscle are myosin and the thin ones actin.

Concept 5 of 5: Nucleotides and nucleic acids in outline

A nucleotide has three parts: a phosphate, a five-carbon sugar and a nitrogen-containing base. Condensation links the phosphate of one nucleotide to the sugar of the next, making a sugar-phosphate backbone with the bases sticking out. The order of the bases is the genetic information. The details of DNA and RNA belong to Molecular Biology.

Definition

A nucleotide = phosphate group + pentose sugar + nitrogenous base.
DNA uses deoxyribose and the bases A, T, G, C. RNA uses ribose and A, U, G, C.
Nucleotides join by condensation into a strand held by phosphodiester bonds between the phosphate of one nucleotide and the sugar of the next.
The two strands of DNA are held together by hydrogen bonds between paired bases (A with T, G with C).
ATP is a nucleotide: adenine, ribose and three phosphate groups.
Enzymes that copy nucleic acids (DNA polymerase, RNA polymerase, reverse transcriptase) all make phosphodiester bonds.

Feature	DNA	RNA
Sugar	Deoxyribose	Ribose
Bases	A, T, G, C	A, U, G, C
Strands	Two, in a double helix	Usually one
Bond within a strand	Phosphodiester	Phosphodiester
Main location in a eukaryotic cell	Nucleus (also mitochondria and chloroplasts)	Nucleus, cytoplasm and ribosomes

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Hydrogen bonds join the strands; phosphodiester bonds join the nucleotides

The covalent phosphodiester bonds make the backbone of each strand. The weak hydrogen bonds between bases hold the two strands of DNA together and let them separate for copying.

Summary — formulas & gotchas at a glance

A revision cheat-sheet for the formulas and gotchas above. Click any concept name to jump back to its full explanation.

Formulas (1)

The peptide bond and the mass of a polypeptide
Mass of a single polypeptide chain
$M = n\,\bar{m} - 18\,(n-1)$

Reference tables (4)

The structure of an amino acid4 rows

Part	Formula	Property
Amino group	$\mathrm{-NH_2}$	Basic; same in all amino acids
Carboxyl group	$\mathrm{-COOH}$	Acidic; same in all amino acids
Hydrogen on the α-carbon	$\mathrm{-H}$	Same in all amino acids
R group (side chain)	Varies (H in glycine, $\mathrm{CH_3}$ in alanine)	Decides polarity, charge and size; the only part that differs

The four levels of protein structure4 rows

Level	What it is	Held by	Example
Primary	Sequence of amino acids	Peptide bonds	Any protein; one change can alter the whole fold (sickle cell haemoglobin)
Secondary	α-helix or β-pleated sheet	Hydrogen bonds in the backbone	α-helices of keratin; β-sheets of silk
Tertiary	3D fold of a single chain	R-group bonds: hydrogen, ionic, disulfide, hydrophobic	Myoglobin (one chain); many enzymes
Quaternary	Several chains together	The same R-group bonds, between chains	Haemoglobin (four chains, each with a haem group); collagen (three chains)

Fibrous and globular proteins, where they act, and denaturation5 rows

Protein	Type	Where it acts	Function
Collagen	Fibrous	Outside cells (extracellular matrix)	Tensile strength of skin, tendon, bone
Keratin	Fibrous	Inside cells of skin, hair and nails	Toughness, waterproofing
Haemoglobin	Globular	Inside red blood cells	Carries oxygen
Antibodies	Globular	Blood plasma and body fluids	Bind antigens
Myosin and actin	Fibrous filaments	Inside muscle cells	Contraction (myosin thick filaments, actin thin filaments)

Nucleotides and nucleic acids in outline5 rows

Feature	DNA	RNA
Sugar	Deoxyribose	Ribose
Bases	A, T, G, C	A, U, G, C
Strands	Two, in a double helix	Usually one
Bond within a strand	Phosphodiester	Phosphodiester
Main location in a eukaryotic cell	Nucleus (also mitochondria and chloroplasts)	Nucleus, cytoplasm and ribosomes

Watch out for (6)

The R group can contain N, O or even its own COOH
→ The structure of an amino acid
Hydrolysis breaks the C-N peptide bond, not a bond inside an R group
→ The peptide bond and the mass of a polypeptide
A protein with a quaternary level still has all the lower levels
→ The four levels of protein structure
Denaturation does not break peptide bonds
→ Fibrous and globular proteins, where they act, and denaturation
Collagen is not a muscle filament
→ Fibrous and globular proteins, where they act, and denaturation
Hydrogen bonds join the strands; phosphodiester bonds join the nucleotides
→ Nucleotides and nucleic acids in outline

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