Amino Acids and Proteins - Vocabulary Flashcards (Chapter 18)
18.1 An Introduction to Biochemistry
Biochemistry/biological chemistry is the study of molecules and reactions in living organisms; includes both inorganic and organic chemical principles from earlier chapters.
Applications across health professions: dieticians/nutritionists, physicians, dentists, physical therapists, trainers, dental hygienists need biochemistry knowledge to provide patient care.
Overall goal of biological chemistry: understand the structure of biomolecules and their direct relationship to function (structure → function).
Biological chemistry vs chemical biology:
Biological chemistry seeks to understand biomolecule structure and function in biology.
Chemical biology aims to synthesize/design organic molecules that mimic or alter action of biomolecules.
Biochemistry is the common ground for life sciences; principal biomolecules: proteins, carbohydrates, lipids, nucleic acids.
Biochemical reactions require three broad activities:
catabolism: continuously degrade food molecules
anabolism: generate biomolecules and store food energy
waste elimination: remove waste products
Despite complexity, functional groups and core reactions are consistent with organic chemistry.
Concept introduced: genotype (genetic makeup) vs phenotype (expressed traits) and their relevance to health and disease.
Important context example: osteogenesis imperfecta (used to illustrate genotype–phenotype link and genetic/metabolic basis of disease).
Functional information from Chapter 18 integrates structure with function across biomolecules.
18.2 Proteins and Their Functions: An Overview
Proteins constitute approximately 50% of body dry weight.
Learning objective: describe the different functions of proteins and give an example for each function.
Etymology: the word protein derives from the Greek proteios meaning “primary,” reflecting their central importance in biology.
Roles of proteins in living systems:
Structural: provide support in tissues (e.g., keratin) and internal framework (actin filaments).
Metabolic control: enzymes catalyze biochemical reactions (e.g., catalase).
Hormonal signaling: hormones regulate body functions (e.g., oxytocin).
Catalysis and metabolism: the enzyme’s overall structure/shape is crucial for function.
Immune function: antibodies rely on protein structure for recognizing pathogens.
Structure–function relationship:
The overall shape and topology of proteins are essential for enzyme catalysis and antibody binding.
Genotype–phenotype connection: changes in sequence alter structure, altering function.
Table 18.2 (Classification of Proteins by Function) (examples):
Enzymes: catalyze biochemical reactions (e.g., Amylase).
Hormones: regulate body functions by signaling to receptors (e.g., Insulin).
Storage proteins: provide essential substances when needed (e.g., Myoglobin stores oxygen).
Transport proteins: move substances through membranes and fluids (e.g., Serum albumin).
Structural proteins: provide mechanical shape/support (e.g., Collagen).
Protective proteins: defend against foreign matter (e.g., Immunoglobulins).
Contractile proteins: perform mechanical work (e.g., Myosin and actin).
18.3 Amino Acids
Proteins are polymers of amino acids; 20 standard α-amino acids.
Learning objectives:
Recognize and describe the 20 α-amino acid structures.
Categorize amino acids by polarity (hydrophilicity) and by the neutral/hydrophobic properties of their side chains.
Explain chirality and identify which amino acids are chiral.
Core structure of an amino acid:
Each amino acid contains an amine (-NH2), a carboxylic acid group (-COOH), a hydrogen, and an R-group (side chain) attached to a central α-carbon.
The four groups are covalently bonded to the α-carbon (the α-carbon is the second carbon in the backbone; the carboxyl carbon is C1).
α-Amino acids and orientation:
They are called α-amino acids because the amino group is on the left and the carboxyl group on the right in Fischer projections.
The side chain (R) varies among the 20 amino acids and determines function.
R-groups determine properties:
Nonpolar (hydrophobic) vs polar (hydrophilic) side chains.
Functional groups: amino, amide, carboxyl, hydroxyl, sulfide, etc.
20 standard amino acids use one-letter and three-letter abbreviations; glycine is special:
Glycine is achiral (R = H).
All other standard amino acids are chiral; 19 are L-forms in biology; D-forms are rare in proteins.
Ionization and pKa context (prelude to 18.4):
At physiological pH (~7.4), amino acids largely exist as zwitterions with
ext{H}_3 ext{N}^+- ext{CH(R)}- ext{COO}^-The R-group identity determines ionization behavior and overall charge at different pH.
Isolated note on abundance and coding:
All proteins in all organisms use the same 20 amino acids.
Each amino acid is defined by a one-letter code, a three-letter code, and a zwitterionic form at physiological pH (7.4).
Chirality details:
Of the 20 amino acids, 19 are chiral; glycine is achiral.
Living systems use L-amino acids for proteins.
18.4 Acid-Base Properties
Zwitterion definition: a neutral, dipolar ion with one positive and one negative charge.
At physiological pH, amino acids exist as zwitterions with + charge on the amino group and - charge on the carboxylate group:
ext{H}_3 ext{N}^+- ext{CH(R)}- ext{COO}^-Ionizable groups in amino acids:
Carboxyl group (-COOH) and amino group (-NH2), whose protonation states vary with pH.
pH-dependent forms:
At very acidic pH (pH ≈ 2–3): carboxylate is protonated to COOH; amino group remains as NH3+, giving an overall positive charge.
At neutral to mildly basic pH (~7.0): the zwitterion form dominates; net charge is zero at the isoelectric point (pI).
At strongly basic pH (pH ≥ 8–9): amino group loses a proton to become -NH2; carboxylate remains -COO−; net negative charge.
Isoelectric point (pI): pH at which amino acid has equal positive and negative charges; net charge is zero.
pI is specific to each amino acid due to its R-group; it influences solubility and participation in enzyme mechanisms.
Special cases for acidic/basic side chains:
Aspartic acid (acidic) → Aspartate in basic solution.
Glutamic acid (acidic) → Glutamate in basic solution.
Side chain ionization and physiological relevance:
Side chain interactions influence protein stability and enzyme active sites.
pI affects protein solubility and participation in catalysis.
Worked Example 18.2 (valine):
At low pH, valine gains protons on acidic groups to become a cationic form; at high pH, carboxyl and amino groups shift to their deprotonated/protonated forms leading to different charge states; valine side chain remains nonpolar.
Conceptual takeaway: nonpolar aliphatic side chains (valine) stay largely uncharged, while terminal groups shift with pH.
18.5 Peptides
Peptide bond: an amide bond joining two amino acids; formation releases water.
Definition and scope:
Dipeptide: two amino acids joined by one peptide bond.
Tripeptide: three amino acids joined by two peptide bonds.
Polypeptide: tens to hundreds of amino acids in a linear chain.
Oligopeptide: several hundred to thousands of amino acids (often used loosely for short polymers).
Directionality and naming:
Peptides/proteins are written with the amino terminus (N-terminal) on the left and carboxyl terminus (C-terminal) on the right.
Residues are the individual amino acids in a peptide chain.
A peptide is named by listing residues from N-terminus to C-terminus.
Peptide bond formation (illustrative):
ext{A{-}COOH} + ext{H}2 ext{N{-}B} ightarrow ext{A{-}CO{-}NH{-}B} + ext{H}2 ext{O}Sequence significance and genetics:
The sequence of amino acids dictates protein structure and function; DNA encodes the sequence; minor DNA/protein sequence variations enable adaptation.
Worked Example 18.3 (Ala-Gly dipeptide):
Ala is the N-terminal amino acid; Gly is the C-terminal.
A peptide bond forms between the carboxylate of alanine and the amino group of glycine.
Structures show the dipeptide where the bond is formed with loss of water.
18.6 Protein Structure: An Overview and Primary Protein Structure (1°)
Primary structure (1°): the linear sequence of amino acids in a protein, linked by peptide bonds.
Representation of the backbone:
Backbone is a chain of alternating α-carbons (-Cα-) and peptide bond atoms (-C–N-).
Side chains (R-groups) project from the α-carbons.
Planar peptide bond and backbone geometry:
Peptide bond carbons and nitrogens are planar; α-carbons have tetrahedral geometry.
Determinants of function:
Primary structure dictates the higher-order structures and ultimately function.
Genetic variations (missense/nonsense mutations) can be deleterious/inherited disease risk; reference DNA sequence defines encoded amino acid sequence.
Examples illustrating sequence–function relationship:
Hormones differing by only two amino acids can have different receptor binding and effects (distinct functions).
Conceptual note:
Primary structure is crucial to function and may underlie debilitating or fatal inherited metabolic diseases.
18.7 Secondary Protein Structure (2°)
Definition: spatial arrangement of the polypeptide chain in local motifs.
Main secondary structures:
α-helix (a-helix): right-handed coil stabilized by hydrogen bonds between the amide hydrogen (N–H) and carbonyl oxygen (C=O) of nearby peptide bonds.
β-sheet (b-sheet): adjacent polypeptide chains held together by hydrogen bonds along the backbones; can be parallel or antiparallel.
Hydrogen bonding pattern:
Hydrogen bonds form between backbone amide N–H (donor) and carbonyl C=O (acceptor).
Structural classification:
Fibrous proteins: form insoluble fibers/sheets (e.g., keratins, collagen, elastin, myosin).
Globular proteins: folded into compact shapes with mostly hydrophobic interiors and hydrophilic surfaces; most enzymes are globular.
Practical exemplars:
Spider silk (fibrous) vs eggs/milk/cheese (globular).
Additional notes:
Proteins are classified by 2° structure and also by functional categories; structure–function relationship is reinforced by organic chemistry principles.
18.8 Tertiary Protein Structure (3°)
Definition: the overall three-dimensional folding of a single polypeptide chain into its unique shape.
Four key interactions stabilizing 3° structure (noncovalent and some covalent):
Hydrogen bonds between backbone and side chains.
Ionic interactions (salt bridges) between charged side chains.
Hydrophilic interactions with water around the protein surface.
Hydrophobic interactions concentrating nonpolar side chains in the core.
Disulfide bonds: covalent S–S bonds between cysteine residues (thiol groups -SH can oxidize to form -S–S-).
Conjugated proteins: proteins that include non-amino acid components that contribute to function.
Heme in myoglobin as an example.
Simple vs conjugated proteins:
Simple proteins consist only of amino acid residues.
Conjugated proteins have non-amino acid moieties and often perform specialized functions.
Notable examples and details:
Hemoglobin: a conjugated quaternary protein with four polypeptide chains (two α and two β) held together by hydrophobic interactions; each chain contains a heme group with Fe2+. Four heme groups enable binding of up to four O2 molecules in lungs; release in tissues for CO2 transport back to lungs.
Collagen: major connective-tissue protein; basic unit is tropocollagen (three intertwined polypeptides ~1000 amino acids per chain). Chains are left-handed; three chains wrap into a right-handed triple helix; glycine every third residue; prolines hydroxylated in a vitamin C–dependent reaction.
Table 18.5: Examples of conjugated proteins (nonprotein parts and examples):
Glycoproteins (carbohydrates) – e.g., cell membranes
Lipoproteins (lipids) – e.g., lipoproteins transporting cholesterol
Metalloproteins (metal ions) – e.g., cytochrome oxidase
Phosphoproteins (phosphate groups) – e.g., casein in milk
Hemoproteins (heme) – e.g., hemoglobin, myoglobin
Nucleoproteins (RNA) – in ribosomes
Summary concepts for 3° structure:
Tertiary structure arises from interactions between R-groups and sometimes backbone atoms, as well as covalent disulfide bonds for stabilization.
The 3° structure underpins the function of enzymes, receptors, transporters, and many other proteins.
18.9 Quaternary Protein Structure (4°)
Definition: interaction between two or more polypeptide chains to form a functional protein complex.
Key features:
Can be stabilized by noncovalent forces (hydrogen bonds, ionic interactions, van der Waals) and sometimes covalent bonds or non-amino acid components.
Example: Hemoglobin as a quaternary protein composed of four polypeptide chains (two α and two β) with four heme groups; interactions stabilize the complex.
Other examples and distinctions:
Serum albumin: non-cellular protein that carries small molecules (lipids, cholesterol) in extracellular fluids; not responsible for O2 transport.
Collagen: basic unit forms a hierarchical quaternary structure (triple helix) contributing to connective tissue resilience.
Practical takeaway:
Quaternary structure involves multiple chains and their assembly, often enabling cooperative binding and functional regulation.
18.10 Chemical Properties of Proteins
Protein hydrolysis definitions:
Hydrolysis is the reverse of protein formation; peptide bonds are cleaved by water to yield amino acids.
In digestion, dietary proteins are hydrolyzed in stomach and small intestine to amino acids for absorption.
In laboratory settings, proteins can be hydrolyzed by heating in aqueous acid (strong acid).
Endoproteases (specific proteolytic enzymes):
Chymotrypsin: hydrolyzes peptide bonds on the carboxyl-terminal side of aromatic amino acids.
Trypsin: hydrolyzes peptide bonds on the carboxyl side of lysine and arginine.
Carboxypeptidases A and B: hydrolyze terminal amino acids from the C-terminus (exopeptidases).
Denaturation vs hydrolysis:
Denaturation: disruption of secondary, tertiary, and quaternary structure without breaking peptide bonds; primary structure remains intact.
Consequences of denaturation: decreased solubility, loss of enzymatic/receptor/transporter function; most denaturation is irreversible, though renaturation may recover some activity.
Determinants of protein shape:
The primary sequence contains all information needed to determine the three-dimensional structure.
Misfolding can lead to abnormal structures and disease states.
Agents that cause denaturation:
Heat: disrupts weak forces stabilizing globular proteins.
Mechanical agitation: e.g., foaming from whipping egg whites.
Detergents: disrupt hydrophobic interactions by solubilizing nonpolar regions.
Organic solvents: interfere with hydrogen bonding.
pH changes: extreme pH disrupts salt bridges and ionic interactions.
Inorganic salts: high ionic strength disrupts ionic interactions.
Concept map takeaway (integrated view):
1° sequence determines 2° motifs (α-helix, β-sheet) via backbone interactions; 3° folding results from side-chain interactions (hydrogen bonds, ionic interactions, hydrophobic effects, disulfide bonds); 4° quaternary assembly arises when multiple polypeptides associate; all levels contribute to function and properties such as solubility and activity.
Worked examples and applications (highlights):
Worked Example 18.1: hydrophobic vs hydrophilic side chains – phenylalanine is hydrophobic (alkyl + phenyl ring); serine is hydrophilic (hydroxyl group).
Worked Example 18.2: valine zwitterion behavior at different pH values; emphasizes that ionization state depends on pH and side-chain identity.
Worked Example 18.3: dipeptide Ala-Gly – identification of N-terminal vs C-terminal residues and the formed peptide bond structure.
Worked Example 18.4: interaction between glutamine and threonine side chains – hydrogen bonding via amide carbonyl with hydroxyl group; not ionic due to non-ionization of hydroxyl.
Worked Example 18.5: hydrogen bonding differences between secondary vs tertiary structures; secondary structure hydrogen bonds occur along the backbone; tertiary structure hydrogen bonds involve side chains.
Worked Example 18.6: classification of structures (primary–4°) with examples; clarifies which features correspond to each level.
Worked Example 18.7: enzymatic hydrolysis by chymotrypsin – identifies fragments produced from vasopressin and determines N- vs C-terminal residues after cleavage.
Concept map and broader context (page 119):
Connects proteins to structure and function (1°–4°), including globular vs fibrous forms.
Illustrates examples like hemoglobin, immunoglobulins, collagen, myosin, etc.
Shows how R-group chemistry drives properties such as polarity, charge, solubility, and folding.
Notable numerical specifics and examples:
Hemoglobin composition: two α-chains (141 aa) and two β-chains (146 aa).
Hemoglobin contains four heme groups with an Fe2+ ion in each, enabling oxygen binding; in lungs, O2 binding is maximized (four O2 per hemoglobin).
Collagen triple-helix structure involves glycine every three residues; proline hydroxylation depends on vitamin C.
Core takeaways for exams:
Understand how amino acid structure (N-terminus, C-terminus, R-group) governs protein folding and function at all four levels of structure.
Recognize major noncovalent and covalent interactions stabilizing structures: hydrogen bonds, ionic/salt-bridges, van der Waals, hydrophobic effects, disulfide bonds.
Be able to distinguish fibrous vs globular proteins and give functional examples.
Be able to describe how enzymatic hydrolysis occurs and how denaturation affects protein function.
Recall key examples of conjugated proteins and their nonprotein components (heme, lipid, carbohydrate, phosphate, metal ions, RNA).
Key formulas and concepts to remember:
General amino acid structure: ext{H}_2 ext{N}{-} ext{CH}( ext{R} ){-} ext{COOH}
Zwitterion at physiological pH: ext{H}_3 ext{N}^+- ext{CH}( ext{R} ){-} ext{COO}^-
Peptide bond formation (loss of water): ext{A{-}COOH} + ext{H}2 ext{N{-}B} ightarrow ext{A{-}CO{-}NH{-}B} + ext{H}2 ext{O}
Valine example of charge changes with pH (conceptual): low pH vs high pH forms depend on protonation states of carboxyl and amino groups.
Ethico-philosophical/practical implications discussed in intro:
Biochemistry provides molecular-level insights into disease mechanisms, enabling targeted therapies.
Understanding genotype–phenotype relationships informs diagnosis and treatment strategies.
The study of protein structure-function relationships underpins drug design, enzyme engineering, and biomaterials development.
Connections to previous lectures/foundational principles:
Reinforces concepts of acid–base chemistry (18.4) and intermolecular forces (8.2) in a biological context.
Applies polymer/monomer principles (18.3) to biological polymers (proteins as amino-acid polymers).
Bridges organic functional groups with biological macromolecules, illustrating structure–function in real systems.
Real-world relevance and examples:
Hemoglobin’s quaternary structure and heme groups underpin oxygen transport in blood.
Collagen structure explains the mechanical properties of connective tissues and the impact of vitamin C on connective tissue integrity.
Protein misfolding and its link to disease underscores the importance of correct folding and chaperone-assisted folding in biology and medicine.
Illustrative terminology recap:
1° structure: amino acid sequence
2° structure: α-helix and β-sheet motifs stabilized by backbone hydrogen bonds
3° structure: overall 3D shape of a single polypeptide driven by R-group interactions and disulfide bonds
4° structure: assembly of multiple polypeptide chains into a functional protein complex
Conjugated proteins: proteins with non-amino acid components (e.g., heme, sugars, lipids)
Summary takeaway:
Protein science integrates organic chemistry, physics, and biology to explain how sequence and chemistry determine structure, stability, and function, with broad implications for health and disease.