Biomolecules

This comprehensive study material, presented by Assoc. Prof. Burcu Bayoğlu, delves into the fundamental biomolecules essential for life, starting with the chemical bonds that hold them together and progressing through the major classes of organic molecules found in cells: carbohydrates, lipids, nucleic acids, and proteins. It covers their structures, functions, and critical roles in cellular processes.

Chemical Bonds

Chemical bonds are the forces that hold atoms together to form molecules, and they are categorized into several types based on the nature of electron interaction.

Covalent Bonds

Definition and Formation: Covalent bonds are the strongest interactions between atoms, formed when two atoms share a pair of electrons. They are responsible for holding atoms together in molecules.
Electron Sharing and Valence:
- Methane (CH₄) is a classic example, where one carbon atom shares electrons with four hydrogen atoms.
- The number of covalent bonds an atom can form is determined by its valence, which is the number of unpaired electrons in its outer electron shell.
- Carbon has four unpaired electrons, allowing it to form four covalent bonds.
- Oxygen has two unpaired electrons, and nitrogen has three, determining their respective bonding capacities in living organisms.
Single vs. Double Bonds:
- Most covalent bonds are single bonds, involving the sharing of a single pair of electrons.
- Some atoms, like carbon, can share two pairs of electrons, forming a double bond (e.g., C=C).
- Double bonds are stronger than single bonds and significantly impact molecular structure.
- Atoms can rotate freely around a single bond (e.g., Ethane C₂H₆), but rotation is restricted around a double bond (e.g., Ethene C₂H₄), leading to rigidity that affects the structure of macromolecules.
Polarity of Covalent Bonds:
- Covalent bonds vary in polarity, which depends on how strongly electrons are attracted to the nuclei of the atoms forming the bond.
- Nonpolar bonds form between atoms of the same element (e.g., C-C) or between atoms with similar electronegativity (e.g., C-H), where electrons are shared equally.
- Electronegativity refers to the differing strengths with which nuclei of different atoms attract electrons.
- Polar bonds form between atoms with significant differences in electronegativity, leading to an uneven distribution of shared electrons.
- Water (H₂O) is a crucial example of a polar molecule. Oxygen is more electronegative than hydrogen, so electrons are drawn closer to the oxygen nucleus. This results in a slight negative charge (δ⁻) on the oxygen atom and slight positive charges (δ⁺) on the hydrogen atoms.

Ionic Bonds

Formation: Strong differences in electronegativity can lead to the complete transfer of electrons from one atom to another, forming ionic bonds.
Example: Sodium Chloride (NaCl):
- Sodium (Na) atoms donate electrons to highly electronegative chlorine (Cl) atoms.
- This forms positively charged sodium ions (Na⁺, cations) and negatively charged chloride ions (Cl⁻, anions).
- These oppositely charged ions are held together by the strong electrostatic attraction of the ionic bond.
Salts: Molecules held together by ionic bonds are called salts. In solid form (e.g., a crystal of sodium chloride), ionic bonds are comparable in strength to covalent bonds.
Dissociation in Aqueous Solutions:
- In aqueous solutions, salts dissociate into individual ions because water molecules, being polar, can interact with and surround the ions.
- The strength of ionic bonds in aqueous solution is significantly reduced, about twentyfold less than covalent bonds.
Critical Inorganic Ions: Many inorganic ions play vital roles in cells, including Na⁺, K⁺, Mg²⁺, Ca²⁺, HPO₄²⁻, Cl⁻, and HCO₃⁻.

Noncovalent Interactions

Beyond covalent and ionic bonds, several weaker noncovalent interactions are crucial for molecular structure and function in biological systems.

Hydrogen Bonds:
- Formation: These noncovalent bonds form between polar molecules. They occur when a positively charged hydrogen atom (δ⁺) in one molecule is attracted to a negatively charged nitrogen or oxygen atom (δ⁻) in another molecule or within the same molecule.
- Examples: Water molecules form hydrogen bonds with each other and with other polar molecules. Hydrogen bonds also form between different organic molecules or within different parts of a large molecule, such as a protein.
- Strength and Role: Hydrogen bonds are approximately fiftyfold weaker than covalent bonds. Despite their individual weakness, their collective strength is significant. They are critical in determining the structures of macromolecules (e.g., proteins and nucleic acids) and governing molecular interactions within cells.
Hydrophobic Interactions:
- Nature: These interactions arise from the polar nature of water. Ions and polar molecules are readily soluble in water (hydrophilic). In contrast, nonpolar molecules, which cannot interact favorably with water, are poorly soluble in an aqueous environment (hydrophobic).
- Mechanism: Nonpolar molecules tend to minimize their contact with water by associating with other hydrophobic molecules. These interactions are not true "bonds" but rather result from the absence of hydrogen or ionic bond formation with the polar solvent (water).
- Examples and Importance: Covalent bonds between carbon and hydrogen are nonpolar. Molecules composed primarily of carbon and hydrogen are insoluble in water and interact with each other instead. Hydrophobic interactions are crucial for protein folding and the formation of lipid bilayers, which are the basic structure of biological membranes.
Van der Waals Interactions:
- Occurrence: These are the fourth type of noncovalent interaction, occurring when any two atoms are in close proximity.
- Cause: They result from transient, fluctuating electrical charges induced by the nearness of molecules.
- Strength: Van der Waals interactions are very weak, less than half the strength of hydrogen bonds.
- Significance: While they occur in both polar and nonpolar molecules, they are generally less significant in polar molecules due to the stronger effects of ionic and hydrogen bonds. However, the cumulative effect of many van der Waals interactions can significantly enhance the association of large nonpolar molecules.

The Molecules of Cells

Cells are complex systems composed of various molecules that dictate their behavior and functions.

Cellular Composition: Cells are primarily composed of water, inorganic ions, and carbon-containing organic molecules.
Impact on Cell Behavior: The specific structures of these molecules are fundamental in determining all aspects of cell behavior.
Four Major Classes of Organic Molecules: Most organic compounds in cells fall into one of four main categories:
- Carbohydrates
- Lipids
- Proteins
- Nucleic acids
Macromolecules:
- Proteins, nucleic acids, and most carbohydrates (polysaccharides) are large macromolecules.
- They are formed through the joining (polymerization) of hundreds or thousands of smaller, low-molecular-weight precursors: amino acids, nucleotides, and simple sugars, respectively.
- These macromolecules constitute a significant portion (80-90%) of the dry weight of most cells.
- Lipids represent the other major constituent of cells.

Carbohydrates

Carbohydrates are a diverse group of organic molecules that include simple sugars and complex polysaccharides, serving various essential roles in cells.

Components: Carbohydrates encompass simple sugars (monosaccharides) and their polymers, polysaccharides.
Primary Functions:
- Nutrients and Energy: Simple sugars, such as glucose, are the primary nutrients for cells. Their breakdown provides cellular energy and serves as starting material for synthesizing other cell constituents.
- Storage and Structure: Polysaccharides function as storage forms of sugars (e.g., starch, glycogen) and as structural components of the cell (e.g., cellulose).
- Informational Markers: Polysaccharides and shorter sugar polymers (oligosaccharides) act as markers for cell recognition processes, cell adhesion, and the transport of proteins to specific intracellular destinations.
Monosaccharides (Simple Sugars):
- Basic Formula: The general formula for monosaccharides is (CH₂O)n, from which the name "carbohydrate" (carbo = carbon, hydrate = water) is derived.
- Glucose (C₆H₁₂O₆): A six-carbon sugar (n=6) that is particularly important in cells as the principal source of cellular energy.
- Diversity: Other simple sugars typically contain between three and seven carbons, with three- and five-carbon sugars being the most common.
- Ring Structures: Sugars with five or more carbons predominantly exist in cyclized ring structures within cells.
- Isomeric Forms: Cyclized sugars can exist in two alternative forms, designated alpha (α) and beta (β), depending on the configuration of carbon 1.
Oligosaccharides and Polysaccharides:
- Formation: Monosaccharides are joined together by dehydration reactions, where a molecule of water (H₂O) is removed, forming a glycosidic bond between two carbons.
- Oligosaccharides: Polymers formed when only a few sugars are joined together.
- Polysaccharides: Macromolecules formed when hundreds or thousands of sugars are linked.
Common Polysaccharides and Their Structures:
- Glycogen and Starch:
  - Function: These are the primary storage forms of carbohydrates for energy utilization in animal cells (glycogen) and plant cells (starch), respectively.
  - Composition: Both are composed entirely of glucose molecules in the α configuration.
  - Linkages: The main linkage is an α-1,4 glycosidic bond between carbon 1 of one glucose and carbon 4 of the next.
  - Branching: Glycogen and one form of starch (amylopectin) also contain occasional α-1,6 linkages, where carbon 1 of one glucose is joined to carbon 6 of another. These α-1,6 linkages create branches by joining two separate α-1,4 linked chains. Another form of starch, amylose, is unbranched.
  - Similarity: The structures and functions of glycogen and starch are fundamentally similar, both serving to store glucose.
- Cellulose:
  - Function: Cellulose has a distinct function as the principal structural component of plant cell walls.
  - Composition: It is also composed entirely of glucose molecules.
  - Configuration and Linkage: Unlike starch and glycogen, the glucose residues in cellulose are in the β configuration. They are linked by β-1,4 bonds, rather than α-1,4 bonds.
  - Structure: The β-1,4 linkage causes cellulose to form long, extended chains that pack side-by-side, creating fibers of immense mechanical strength. Cellulose is an unbranched polysaccharide.
- Chitin:
  - Animal Parallel: Chitin is the animal equivalent of cellulose.
  - Composition: It is a polysaccharide made of modified glucose residues linked by β bonds.
  - Function: Chitin forms the exoskeletons of crabs and insects, providing structural support.
Informational Roles of Oligosaccharides and Polysaccharides:
- Beyond energy storage and structural roles, these sugar polymers are vital in informational processes.
- Protein Modification: Oligosaccharides are frequently linked to proteins, influencing protein folding and acting as markers for targeting proteins to the cell surface or specific subcellular organelles.
- Cell Recognition: Both oligosaccharides and polysaccharides serve as markers on cell surfaces, playing crucial roles in cell recognition and mediating interactions between cells in multicellular organisms' tissues.

Lipids

Lipids are a diverse group of hydrophobic molecules with three major roles in cells: energy storage, membrane formation, and signaling.

Major Roles in Cells:
- Energy Storage: Lipids provide an important and efficient form of energy storage.
- Cell Membranes: They are the major components of cell membranes, crucial for cellular integrity and function.
- Cell Signaling: Lipids play significant roles in cell signaling, acting as steroid hormones (e.g., estrogen, testosterone) and as messenger molecules that transmit signals from cell surface receptors to intracellular targets.
Fatty Acids:
- Simplest Lipids: Fatty acids are the simplest form of lipids.
- Structure: They consist of long hydrocarbon chains, most commonly containing 16 or 18 carbon atoms, terminating with a carboxyl group (COO⁻) at one end.
- Saturated vs. Unsaturated:
  - Saturated fatty acids (e.g., palmitate C₁₆, stearate C₁₈) have hydrocarbon chains where all carbon atoms are bonded to the maximum number of hydrogen atoms, meaning they contain no double bonds between carbon atoms.
  - Unsaturated fatty acids (e.g., oleate C₁₈) contain one or more double bonds between carbon atoms. A double bond, such as between carbons 9 and 10 in oleate, introduces a kink in the hydrocarbon chain.
- Hydrophobic Nature: The long hydrocarbon chains of fatty acids are composed primarily of nonpolar C-H bonds, making them unable to interact with water. This hydrophobic nature is fundamental to the behavior of complex lipids, especially in the formation of biological membranes.
Triacylglycerols (Triglycerides or Fats):
- Storage Form: Fatty acids are stored in the form of triacylglycerols.
- Structure: These molecules consist of three fatty acids linked to a glycerol molecule. (An example shows three palmitate fatty acids joined to glycerol).
- Solubility and Accumulation: Triacylglycerols are insoluble in water and accumulate as fat droplets within the cytoplasm.
- Energy Yield: When energy is required, triacylglycerols can be broken down. Fats are a highly efficient form of energy storage, yielding more than twice as much energy per weight compared to carbohydrates. This efficiency is particularly important for mobile animals, as it allows for energy storage with less body weight.
Phospholipids:
- Membrane Components: Phospholipids are the principal components of cell membranes.
- General Structure: They consist of two fatty acids joined to a polar head group.
- Glycerol Phospholipids:
  - In these phospholipids, two fatty acids are bound to carbon atoms in glycerol, similar to triacylglycerols.
  - The third carbon of glycerol, however, is bound to a phosphate group. This phosphate group is frequently attached to another small polar molecule, such as ethanolamine, choline, serine, or inositol.
- Sphingomyelin:
  - This is the only nonglycerol phospholipid found in cell membranes.
  - It contains two hydrocarbon chains linked to a polar head group derived from serine, rather than glycerol.
- Amphipathic Nature: All phospholipids are amphipathic molecules, meaning they have both hydrophobic and hydrophilic regions.
  - They possess hydrophobic tails (consisting of the two hydrocarbon chains).
  - They have hydrophilic head groups (comprising the phosphate group and its polar attachments).
  - This amphipathic property is the fundamental basis for the formation of biological membranes.
Other Membrane Lipids: Glycolipids and Cholesterol:
- Glycolipids:
  - Many cell membranes contain glycolipids in addition to phospholipids.
  - Glycolipids consist of two hydrocarbon chains linked to polar head groups that contain carbohydrates (e.g., glucose).
  - Similar to phospholipids, they are amphipathic molecules in their general organization.
- Cholesterol:
  - Cholesterol's structure differs from linear hydrocarbon chains; it consists of four hydrocarbon rings.
  - The hydrocarbon rings are strongly hydrophobic.
  - However, a hydroxyl (OH) group attached to one end of cholesterol is weakly hydrophilic, making cholesterol an amphipathic molecule.
  - Cholesterol is an important component of cell membranes and serves as a precursor for steroid hormones like testosterone and estradiol (a form of estrogen).
Lipids as Signaling Molecules:
- Beyond their roles in membranes, lipids function as signaling molecules both within and between cells.
- Steroid Hormones: Steroid hormones, such as testosterone and estrogens, are derivatives of cholesterol. These hormones are a diverse group of chemical messengers, all characterized by four hydrocarbon rings with distinct functional groups attached.
- Phospholipid Derivatives: Derivatives of phospholipids also act as messenger molecules within cells. They convey signals from cell surface receptors to intracellular targets, regulating a wide array of cellular processes, including cell proliferation, movement, survival, and differentiation.

Nucleic Acids

Nucleic acids, DNA and RNA, are the principal informational molecules of the cell, crucial for genetic information storage, expression, and cellular activities.

Principal Informational Molecules: DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are the core molecules for carrying genetic information.
Roles of DNA:
- DNA has a unique role as the genetic material.
- In eukaryotic cells, DNA is primarily located in the nucleus.
Roles of RNA: Different types of RNA participate in a variety of cellular activities:
- Messenger RNA (mRNA): Carries genetic information from DNA to the ribosomes, where it serves as a template for protein synthesis.
- Ribosomal RNA (rRNA) and Transfer RNA (tRNA): Both are directly involved in the process of protein synthesis.
- Regulation and Processing: Other types of RNAs are involved in regulating gene expression and in the processing and transport of both RNAs and proteins.
- Catalytic Activity: RNA is also capable of catalyzing chemical reactions, including those involved in protein synthesis and RNA processing.
Structure of Nucleic Acids:
- Nucleic acids are polymers of nucleotides.
- Each nucleotide consists of three components: a purine or pyrimidine base, a sugar, and one or more phosphate groups.
- Bases:
  - Purines: Adenine (A) and Guanine (G).
  - Pyrimidines: Cytosine (C) and Thymine (T) in DNA; Cytosine (C) and Uracil (U) in RNA (Uracil replaces Thymine in RNA).
- Sugars:
  - DNA contains 2'-deoxyribose.
  - RNA contains ribose.
- Nucleosides: A nucleic acid base linked to a sugar alone is called a nucleoside.
- Nucleotides: Nucleotides additionally contain one or more phosphate groups linked to the 5' carbon of the nucleoside sugar.
Polymerization of Nucleotides:
- Nucleotides are joined together to form nucleic acids through the formation of phosphodiester bonds.
- A phosphodiester bond forms between the 5' phosphate group of one nucleotide and the 3' hydroxyl group of another nucleotide.
- Oligonucleotides: Small polymers containing only a few nucleotides.
- Polynucleotides: Large polymers that make up cellular RNA and DNA, containing thousands or even millions of nucleotides, respectively.
Directionality of Nucleotide Chains:
- A nucleotide chain has a distinct sense of direction.
- One end terminates in a 5' phosphate group, and the other end terminates in a 3' hydroxyl group.
- Polynucleotides are always synthesized in the 5' to 3' direction, with new nucleotides being added to the 3' OH group of the growing chain.
Information Storage and Replication:
- Information Conveyance: The information in DNA and RNA is conveyed by the specific order of the bases within the polynucleotide chain.
- DNA as a Double Helix: DNA is a double-stranded molecule composed of two polynucleotide chains. These chains run in opposite directions (antiparallel) with respect to their 5' and 3' ends.
- Complementary Base Pairing: The bases are located on the inside of the molecule and are joined by hydrogen bonds between specific complementary base pairs:
  - Guanine (G) pairs with Cytosine (C).
  - Adenine (A) pairs with Thymine (T).
- Template for Synthesis: A crucial consequence of this complementary base pairing is that one strand of DNA (or RNA) can act as a template to direct the synthesis of a complementary strand.
- Self-Replication and Control: Nucleic acids are uniquely capable of directing their own replication, allowing them to function as the fundamental informational molecules of the cell. The information carried by DNA and RNA ultimately directs the synthesis of specific proteins, which control most cellular activities.
Other Critical Roles of Nucleotides:
- Beyond being building blocks of nucleic acids, nucleotides play critical roles in other cellular processes.
- ATP (Adenosine 5'-triphosphate): The most prominent example, ATP is the principal form of chemical energy within cells.
- Energy and Chemical Group Carriers: Other nucleotides function as carriers of energy or reactive chemical groups in a wide variety of metabolic reactions.
- Signaling Molecules: Some nucleotides, such as cyclic AMP (cAMP), are important signaling molecules within cells.

Proteins

Proteins are the most diverse and functionally critical macromolecules in cells, executing tasks directed by genetic information and performing a vast array of functions.

Primary Responsibility: While nucleic acids store genetic information, proteins are primarily responsible for executing the tasks dictated by that information.
Diversity and Functions:
- Proteins are the most diverse of all macromolecules.
- Each cell contains thousands of different proteins, performing a wide variety of functions.
- Roles include:
  - Structural components of cells and tissues.
  - Transport of small molecules (e.g., glucose, nutrients) into cells.
  - Information transmission between cells (e.g., protein hormones).
  - Defense against infection (e.g., antibodies).
  - Enzymes: The most fundamental property of proteins is their ability to act as enzymes, catalyzing nearly all chemical reactions in biological systems.
- Ultimately, proteins direct all activities of the cell.
Amino Acid Structure:
- Proteins are polymers synthesized from 20 different amino acids.
- Each amino acid consists of a central carbon atom, called the α carbon.
- The α carbon is bonded to four groups:
  - A carboxyl group (COO⁻)
  - An amino group (NH₃⁺)
  - A hydrogen atom (H)
  - A distinctive side chain (designated R)
- At physiological pH, both the carboxyl and amino groups are ionized.
Amino Acid Side Chains and Their Properties:
- The specific chemical properties of the R side chains determine the roles of each amino acid in protein structure and function.
- Amino acids are grouped into four broad categories based on their side chain properties:
- Nonpolar Amino Acids:
  - These ten amino acids have side chains that do not interact with water; they are hydrophobic.
  - They tend to be located in the interior of proteins or within membranes, away from water.
  - Glycine: The simplest, with a side chain consisting only of a hydrogen atom.
  - Alanine, Valine, Leucine, Isoleucine: Have hydrocarbon side chains with up to four carbon atoms.
  - Phenylalanine and Tryptophan: Possess very hydrophobic side chains containing aromatic rings.
  - Proline: Unique because its hydrocarbon side chain is bonded to both the nitrogen of the amino group and the α carbon, forming a cyclic structure.
  - Cysteine and Methionine: Contain sulfur atoms. Methionine is quite hydrophobic. Cysteine is less hydrophobic due to its sulfhydryl (SH) group. The sulfhydryl group of cysteine is crucial for protein structure because it can form covalent disulfide bonds between different cysteine residues, stabilizing folded protein structures.
- Polar (Uncharged) Amino Acids:
  - Five amino acids have uncharged but polar side chains.
  - These include Serine, Threonine, and Tyrosine (which have hydroxyl groups on their side chains).
  - Also includes Asparagine and Glutamine (which have polar amide [O=C-NH₂] groups).
  - Because their polar side chains can form hydrogen bonds with water, these amino acids are hydrophilic and are typically found on the outside surface of proteins.
- Basic (Charged) Amino Acids:
  - Lysine, Arginine, and Histidine have side chains with charged basic groups (substances that provide OH⁻ ions in water).
  - Lysine and Arginine are very basic and their side chains are positively charged in the cell, making them very hydrophilic and located on the protein surface.
  - Histidine can be either uncharged or positively charged at physiological pH, allowing it to play an active role in enzymatic reactions involving the exchange of hydrogen ions.
- Acidic (Charged) Amino Acids:
  - Aspartic acid and Glutamic acid have acidic side chains terminating in carboxyl groups (acids provide H⁺ ions in water).
  - These amino acids are negatively charged within the cell and are often referred to as aspartate and glutamate.
  - Like basic amino acids, they are very hydrophilic and are usually located on the surface of proteins.
Polypeptide Formation:
- Peptide Bonds: Amino acids are joined together by peptide bonds, which form between the α carboxyl group of one amino acid and the α amino group of a second amino acid. This is a dehydration reaction.
- Polypeptides: The resulting linear chains of amino acids are called polypeptides, typically hundreds or thousands of amino acids in length.
- Termini: Each polypeptide chain has two distinct ends:
  - The amino (N) terminus, terminating in an amino group.
  - The carboxyl (C) terminus, terminating in a carboxyl group.
- Synthesis Direction: Polypeptides are synthesized from the amino to the carboxy terminus.
Protein Sequence and Conformation:
- Specific Amino Acid Sequences: Proteins are polypeptides with specific amino acid sequences.
- Sanger's Experiment: In 1953, Frederick Sanger first determined the complete amino acid sequence of a protein, the hormone insulin. Insulin consists of two polypeptide chains joined by disulfide bonds between cysteine residues. This experiment revealed that each protein has a unique, specific amino acid sequence.
- Current Knowledge: Protein sequences are now commonly deduced from mRNA sequences, and over 100,000 protein sequences have been established. Each sequence is unique and determined by the order of nucleotides in a gene.
- Three-Dimensional Conformations: The amino acid sequence is only the first element of protein structure. Rather than being extended chains, proteins adopt distinct three-dimensional conformations that are critical for their function. These shapes are determined by interactions between their constituent amino acids.
- Denaturation and Refolding: Christian Anfinsen's experiments demonstrated that disrupting the 3D structures of proteins (denaturation) by treatments like heating (which breaks noncovalent bonds) could be reversed. Denatured proteins often spontaneously refolded to their native conformations, proving that the amino acid sequence directly determines the protein's final 3D structure.
- X-ray Crystallography: This high-resolution technique is frequently used to analyze the 3D structure of proteins. A beam of X-rays directed at protein crystals scatters in characteristic patterns (diffraction patterns), from which the arrangement of individual atoms in the molecule can be deduced. John Kendrew (1958) was the first to determine the 3D structure of myoglobin, a 153-amino acid protein involved in oxygen transport, folded around a heme group.
- Globular vs. Fibrous Proteins: Most proteins, like myoglobin, are globular molecules with polypeptide chains folded into compact structures. Some, such as structural proteins of connective tissues, are long fibrous molecules.
- Complexity of Folding: While analysis of 3D structures has revealed principles of protein folding, predicting the 3D structure directly from an amino acid sequence remains a complex challenge.
Levels of Protein Structure: Protein structure is generally described in four hierarchical levels:
Primary Structure:
- This is the linear sequence of amino acids in the polypeptide chain.
Secondary Structure:
- This refers to the regular arrangement of amino acids within localized regions of the polypeptide.
- These structures are held together by hydrogen bonds between the CO and NH groups of peptide bonds.
- Two common types are:
  - α-helix: A region of the polypeptide chain coils around itself. A hydrogen bond forms between the CO group of one peptide bond and the NH group of a peptide bond located four residues downstream in the linear sequence.
  - β-sheet: Two parts of a polypeptide chain lie side-by-side, connected by hydrogen bonds between them. β-sheets can be formed between several polypeptide strands, which can be oriented in either parallel or antiparallel directions relative to each other.
Tertiary Structure:
- This describes the overall folding of a single polypeptide chain, resulting from interactions between the side chains of amino acids located in different regions of the primary sequence.
- Domains: The basic units of tertiary structure are called domains. These are folded three-dimensional structures typically containing between 50 and 200 amino acids. Small proteins (e.g., ribonuclease, myoglobin) may have a single domain, while larger proteins (e.g., β-glucuronidase) can have multiple domains, often associated with distinct functions.
- Determinants of Tertiary Structure:
  - A critical determinant is the localization of hydrophobic amino acids in the protein's interior and hydrophilic amino acids on its surface, where they interact with water.
  - The interiors of folded proteins primarily consist of hydrophobic amino acids arranged in α-helices and β-sheets. These secondary structures are found in the hydrophobic cores because hydrogen bonding neutralizes the polar character of the CO and NH groups of the polypeptide backbone.
  - Loop regions connecting secondary structure elements are found on the surface, where polar components of peptide bonds form hydrogen bonds with water or with polar side chains of hydrophilic amino acids.
  - Interactions between polar amino acid side chains (hydrogen bonds and ionic bonds) on the protein surface are also important.
  - Covalent disulfide bonds between the sulfhydryl groups of cysteine residues further stabilize the folded structures of many cell surface or secreted proteins.
Quaternary Structure:
- This is the fourth level of protein structure, involving the interactions between different polypeptide chains in proteins composed of more than one polypeptide.
- Example: Hemoglobin: Hemoglobin is composed of four polypeptide chains (two α chains and two β chains, which are identical), each bound to a heme group. These chains are held together by the same types of interactions that maintain tertiary structure.
Overall Complexity and Diversity: The distinct chemical characteristics of the 20 different amino acids lead to considerable variation in the three-dimensional conformations of folded proteins. This inherent complexity and diversity make proteins an extremely versatile group of macromolecules, perfectly suited to perform the wide variety of tasks required in cell biology.

Biomolecules: Chemical Bonds, Cellular Molecules, Carbohydrates, Lipids, Nucleic Acids, and Proteins

Biomolecules: Chemical Bonds, Cellular Molecules, Carbohydrates, Lipids, Nucleic Acids, and Proteins