Amino Acids, Proteins, Enzymes, and Lipids: Core Concepts in Biochemistry

Amino Acids

Structure of Amino Acids

Amino acids are the building blocks of proteins, each consisting of a central carbon atom (the α-carbon) bonded to four distinct groups:

• Basic amino group (NH2)

• Acidic carboxyl group (COOH)

• Variable side chain (R)

• Hydrogen atom

Natural amino acids exhibit L-chirality at the α-carbon, which is crucial for biological function.

Properties of Amino Acids

• Colourless and crystalline

• Soluble in water, acid, and alkali; generally insoluble in organic solvents

• Zwitterionic nature: Can act as both acid and base, existing as cation, zwitterion, or anion depending on pH

Example: At physiological pH, amino acids exist predominantly as zwitterions, with the amino group protonated and the carboxyl group deprotonated.

Classification of Amino Acids

There are 20 naturally occurring amino acids, each identified by a name, three-letter code, and single-letter code.

Name	TLC	SLC	Name	TLC	SLC
Alanine	Ala	A	Leucine	Leu	L
Arginine	Arg	R	Lysine	Lys	K
Asparagine	Asn	N	Methionine	Met	M
Aspartic acid	Asp	D	Phenylalanine	Phe	F
Cysteine	Cys	C	Proline	Pro	P
Glutamic acid	Glu	E	Serine	Ser	S
Glutamine	Gln	Q	Threonine	Thr	T
Glycine	Gly	G	Tryptophan	Trp	W
Histidine	His	H	Tyrosine	Tyr	Y
Isoleucine	Ile	I	Valine	Val	V

Types of Amino Acids by Side Chain

• Non-polar side chains: Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Proline (reduced solubility in water)

• Aromatic side chains: Phenylalanine, Tyrosine, Tryptophan

• Polar uncharged side chains: Serine, Threonine, Cysteine, Asparagine, Glutamine (contain hydroxyl, sulfhydryl, or amide groups)

• Positively charged side chains: Lysine, Arginine, Histidine (second amino group, basic)

• Negatively charged side chains: Aspartic acid, Glutamic acid (second acidic group)

Proteins

Functions of Proteins

Proteins are essential macromolecules with diverse biological roles:

• Structural: Collagen (bone, cartilage, tendon), keratin (hair), actin (muscle)

• Enzymatic: Amylase, pepsin, catalase

• Transport: Haemoglobin (oxygen), transferrin (iron)

• Pumps: Na+, K+ pump in cell membranes

• Motors: Myosin (muscle), kinesin (cilia)

• Hormones: Insulin

• Receptors: Rhodopsin (light receptor in retina)

• Antibodies: Immunoglobulins

• Storage: Albumins in eggs and blood, casein in milk

• Blood clotting: Thrombin, fibrin

• Lubrication: Glycoproteins in synovial fluid

• Toxins: Diphtheria toxin

• Antifreeze: Glycoproteins in arctic flea

Levels of Protein Structure

Primary Structure

The primary structure is the linear sequence of amino acids in a polypeptide chain, determined by genetic information and written from the N-terminus to the C-terminus.

• Defines the 3D structure and biological function of the protein.

Secondary Structure

The secondary structure refers to regular, repeating structures formed by hydrogen bonding between the backbone amide and carbonyl groups.

• α-Helix: Each carbonyl oxygen H-bonded to an amide hydrogen 4 residues ahead; forms a spiral structure.

• β-Pleated Sheet: Protein folds into strands; strands alternate between donating and receiving H-bonds; can be parallel or antiparallel.

Tertiary Structure

The tertiary structure is the overall three-dimensional shape of a single polypeptide chain, stabilized by interactions between R groups:

• Van der Waals bonds (weak, multiple)

• Hydrogen bonds (weak, multiple)

• Ionic bonds (between positive and negative side chains)

• Disulfide bridges (strong covalent S-S bonds between cysteines)

Quaternary Structure

The quaternary structure arises when multiple polypeptide chains (subunits) associate to form a functional protein.

• Example: Haemoglobin (4 globular peptides)

Example: Haemoglobin

• Composed of two copies of two different polypeptides

• Each chain binds a heme group containing Fe2+

• Binding of oxygen to one heme promotes binding to others (cooperativity)

• Heterotetrameric structure enables rapid oxygen binding and release

Protein Classification by Shape

• Globular proteins: Ball-like, soluble, e.g., haemoglobin, myoglobin, pepsin, trypsin, lysozyme

• Fibrous proteins: Long, thin, structural, insoluble, e.g., silk, collagen, myosin, actin

Enzymes

Nature and Function

Enzymes are proteins that act as biological catalysts, accelerating chemical reactions without being consumed.

• ~40,000 different enzymes in human cells

• Highly specific for substrates and reactions

• Increase reaction rates by factors of 106 to 1012

Kinetics of Enzymes

Enzymes lower the activation energy ($riangle G^{ ext{‡}}$) required for a reaction to proceed.

• Active site shape and charge are complementary to the substrate

• Substrate binding facilitates bond breaking or formation

Lipids

General Properties

• Chemically heterogeneous group; no general formula

• Hydrophobic (insoluble in water), soluble in organic solvents

• Do not form large polymers

• Function as energy stores, signaling molecules, and major membrane components

• Store more energy than carbohydrates (37 kJ/g)

Classification of Lipids

• Fatty acids (saturated and unsaturated)

• Glycerides (glycerol-containing lipids)

• Non-glycerides (steroids, waxes)

• Complex lipids (lipoproteins)

Saturated Fatty Acids

• No double bonds in the hydrocarbon chain

• Fit together tightly; higher melting points; usually solid at room temperature

Unsaturated Fatty Acids

• One or more double bonds in the hydrocarbon chain

• Monounsaturated: One double bond

• Polyunsaturated: Multiple double bonds

• Double bonds cause kinks, preventing close packing; lower melting points

• Cis (same side, bent, common) vs. Trans (opposite sides, straight, rare)

Sources of Fats

• Unsaturated: Double bonds, bulky, low melting point, liquid oils (e.g., fish, avocado, nuts)

• Saturated: No double bonds, pack well, high melting point, solid fats (e.g., butter, cheese, chips)

Triglycerides

• Composed of glycerol (propan-1,2,3-triol) and three fatty acids

• Formed by esterification: condensation reaction, loss of water per ester bond

• $ext{Glycerol} + 3 ext{Fatty Acids} ightarrow ext{Triglyceride} + 3 ext{H}_2 ext{O}$

Saponification

• Hydrolysis of triglycerides in basic conditions to produce soap molecules

• $ext{Triglyceride} + 3 ext{NaOH} ightarrow ext{Glycerol} + 3 ext{Soap molecules}$

Phospholipids

• Structurally similar to triglycerides, but with two fatty acids and a phosphate group on the third hydroxyl of glycerol

• Head group is polar (phosphate and N(CH3)3), tail is hydrophobic

• Common head groups: choline, inositol, serine

Properties of Phospholipids

• Amphipathic: possess both hydrophilic and hydrophobic regions

• Spontaneously arrange into bilayers in aqueous solution

Effects on Membrane Properties

• Saturated hydrocarbon tails: viscous membrane

• Unsaturated tails (with kinks): fluid membrane

Steroids

• Core structure: four fused hydrocarbon rings

• Vital components of biological membranes

• Many possible modifications; often function as intercellular signals

Cholesterol

• Essential for cell membrane structure

• Makes lipid bilayer less deformable, decreases permeability to small molecules

• Prevents crystallization and phase shifts in the membrane

High and Low Density Lipoproteins (HDL & LDL)

HDL Function	LDL Effects
Builds and maintains cell membranes Production of bile Important for nervous system function Absorption of lipid-soluble vitamins Precursor for steroid hormone production	Can clog arteries Can lead to coronary heart disease Can lead to heart attack Can lead to stroke

Additional info: HDL is often referred to as "good cholesterol" due to its protective effects, while LDL is "bad cholesterol" due to its association with cardiovascular disease.