Amines, Amides, Amino Acids, Proteins, and Enzymes: Structured Study Notes

Amines and Amides

Heterocyclic Amines

Heterocyclic amines are cyclic organic compounds containing nitrogen atoms within the ring structure. These rings may consist of five or six atoms, with one or two nitrogen atoms present.

• Pyrrolidine: Five-membered ring with four carbon atoms and one nitrogen atom, all single bonds.

• Pyrrole: Five-membered ring with one nitrogen atom and two double bonds.

• Imidazole: Five-membered ring with two nitrogen atoms.

• Piperidine: Six-membered ring with one nitrogen atom; found in black pepper.

• Purine and Pyrimidine: Found in DNA and RNA; purine combines a six-membered pyrimidine and a five-membered imidazole ring.

Alkaloids

Alkaloids are physiologically active compounds produced by plants that contain heterocyclic amines. They are used in anesthetics, antidepressants, and stimulants, and many are habit-forming.

Neurotransmitters

A neurotransmitter is a chemical compound that transmits impulses from a nerve cell to a target cell (another nerve cell, muscle cell, or gland cell). Neurotransmitters contain nitrogen atoms as amines and alkylammonium ions, and are synthesized from amino acids obtained from the diet.

• Important neurotransmitters: acetylcholine, dopamine, norepinephrine, epinephrine, serotonin, histamine, glutamate, GABA.

• Histamine causes allergic reactions and stimulates acid production in the stomach.

• Antihistamines block histamine receptors to stop allergic reactions.

Amides

Amides are derivatives of carboxylic acids where a nitrogen group (—NH2) replaces the hydroxyl (—OH) group. Amides do not exhibit the basic properties of amines and are generally water soluble if they have fewer than six carbons.

Amino Acids and Proteins

Proteins: Structure and Function

Proteins are polymers made from 20 different amino acids. Their characteristics and functions depend on the sequence of amino acids. Proteins serve as structural components, enzymes, and transporters, and are involved in oxygen transport (hemoglobin, myoglobin).

• Structural: Collagen, keratin

• Contractile: Myosin, actin

• Transport: Hemoglobin, lipoproteins

• Storage: Casein, ferritin

• Hormone: Insulin, growth hormone

• Enzyme: Sucrase, trypsin

• Protection: Immunoglobulins

Amino Acid Structure

Amino acids are the building blocks of proteins. Each amino acid has a central α carbon bonded to:

• An ammonium group (—NH3+)

• A carboxylate group (—COO−)

• A hydrogen atom

• An R group (side chain)

Zwitterion

At physiological pH, amino acids exist as zwitterions, with both positive (ammonium) and negative (carboxylate) charges, resulting in an overall neutral molecule. The pH at which this occurs is called the isoelectric point (pI).

Classification of Amino Acids

Amino acids are classified based on their R groups:

• Nonpolar (hydrophobic): Hydrogen, alkyl, or aromatic R groups

• Polar (hydrophilic): R groups interact with water

• Polar neutral: Hydroxyl (—OH), thiol (—SH), or amide (—CONH2) R group

• Polar acidic: Carboxylic acid (—COOH) R group

• Polar basic: Amine (—NH2) R group

Essential Amino Acids

Of the 20 amino acids, 11 can be synthesized by the body, while 9 are essential amino acids that must be obtained from the diet.

Peptide Bonds and Protein Structure

A peptide bond is an amide bond formed between the —COO− group of one amino acid and the —NH3+ group of another. Peptides are chains of amino acids:

• Dipeptide: 2 amino acids

• Tripeptide: 3 amino acids

• Tetrapeptide: 4 amino acids

• Pentapeptide: 5 amino acids

• Polypeptide: More than 5 amino acids

• Protein: Polypeptide with 50+ amino acids and biological activity

Primary Structure

The primary structure of a protein is the sequence of amino acids held together by peptide bonds from the N-terminus to the C-terminus.

Secondary Structure

The secondary structure describes the arrangement of the polypeptide backbone stabilized by hydrogen bonds.

• Alpha (α) helix: Hydrogen bonds form between C=O and N-H groups, creating a helical shape.

• Beta (β) pleated sheet: Hydrogen bonds form between C=O and N-H groups in adjacent sections, resulting in a zig-zag sheet.

Tertiary Structure

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

• Hydrophilic interactions: Polar residues interact with water, pulling them to the protein's surface.

• Hydrophobic interactions: Nonpolar residues cluster in the protein's interior.

• Salt bridges: Ionic attractions between acidic and basic residues.

• Hydrogen bonds: Between polar residues.

• Disulfide bonds: Covalent bonds between cysteine residues.

Quaternary Structure

Proteins with two or more polypeptide chains have a quaternary structure. Hemoglobin, for example, consists of four subunits (two orange, two red chains).

Protein Hydrolysis and Denaturation

Denaturation occurs when the interactions stabilizing secondary, tertiary, or quaternary structures are disrupted, destroying the protein's shape and biological activity. Causes include heat, acid, base, heavy metal salts, and agitation.

Enzymes and Vitamins

Enzyme Structure and Function

Enzymes are globular proteins that increase the rate of chemical reactions by lowering the activation energy. They have a unique three-dimensional shape with an active site where substrates bind.

• Enzyme-substrate (ES) complex forms, providing an alternative pathway with lower activation energy.

• Amino acid R groups in the active site catalyze the reaction, forming an enzyme-product (EP) complex.

Models of Enzyme Action

• Lock-and-key model: Rigid substrate binds to rigid enzyme, like a key fitting a lock.

• Induced-fit model: Active site adapts to the substrate's shape, lowering activation energy.

Classification of Enzymes

Enzymes are classified into six types based on the reactions they catalyze:

• Oxidoreductases: Catalyze oxidation-reduction reactions

• Transferases: Transfer functional groups between compounds

• Hydrolases: Catalyze hydrolysis (add H2O) to split molecules

• Lyases: Add or remove groups without hydrolysis

• Isomerases: Rearrangement (isomerization) of atoms within a substrate

• Ligases: Join two substrates using ATP energy

Factors Affecting Enzyme Activity

• Optimum temperature: Most active at 37°C in humans

• Low temperature: Little activity

• High temperature (>50°C): Denaturation occurs, activity lost

• Optimum pH: Usually 7.4, but varies by organ

Enzyme and Substrate Concentration

• Increasing enzyme concentration (constant substrate): Increases reaction rate

• Increasing substrate concentration (constant enzyme): Increases reaction rate until enzyme is saturated, then activity plateaus

Summary Table: Protein Functions

Class of Protein	Function	Examples
Structural	Provide structural components	Collagen (tendons, cartilage), Keratin (hair, skin, wool, nails)
Contractile	Make muscles move	Myosin, Actin
Transport	Carry substances throughout body	Hemoglobin, Lipoproteins
Storage	Store nutrients	Casein (milk), Ferritin (spleen, liver)
Hormone	Regulate metabolism and nervous system	Insulin, Growth hormone
Enzyme	Catalyze biochemical reactions	Sucrase, Trypsin
Protection	Recognize and destroy foreign substances	Immunoglobulins

Key Equations

• Peptide bond formation: $\mathrm{R_1{-}COO^- + R_2{-}NH_3^+ \rightarrow R_1{-}CO{-}NH{-}R_2 + H_2O}$

• Enzyme-catalyzed reaction: $\mathrm{E + S \rightarrow ES \rightarrow E + P}$

Additional info:

• Protein denaturation is irreversible in most cases, especially when caused by heat or strong chemicals.

• Enzyme activity is crucial for metabolic pathways and is regulated by inhibitors, activators, and environmental conditions.