Fundamentals of Biomolecules and Cellular Energy Dynamics

Introduction to Biomolecules

Living organisms are made up of thousands of biomolecules—molecules produced by living systems with distinct properties and functions favored through evolution. Small, simple molecules called micromolecules (or monomers), such as water, minerals, simple sugars, and nucleotides, serve as building blocks for larger macromolecules (or polymers) like proteins, lipids, carbohydrates, and nucleic acids. Biomolecules are classified into inorganic types (e.g., water, minerals, gases) and organic types (e.g., lipids, carbohydrates, proteins, nucleic acids). While biomolecules alone do not exhibit life, they organize into cells and are continuously synthesized and broken down to maintain and perpetuate life.

Water: The Essential Inorganic Biomolecule

Physical and Chemical Properties of Water

• Cohesive and adhesive: Water molecules stick to each other and other surfaces.
• High specific heat: Requires a lot of energy to change temperature, helping stabilize environments.
• High thermal conductivity: Efficiently transfers heat.
• High boiling and freezing points: Water boils and freezes at relatively high temperatures compared to similar molecules.
• Good evaporative coolant: Evaporation of water cools surfaces.
• Less dense as solid: Ice floats because solid water is less dense than liquid.
• Polarity: Water molecules have partial positive (H) and negative (O) charges, making them interact strongly with charged molecules (hydrophilic) and poorly with non-charged ones (hydrophobic).
• Ionization: Water dissociates into H⁺ and OH⁻ ions, influencing chemical reactions.

Biological Significance of Water

• Origin of life: Life likely began in water.
• Abundance: Makes up over 70% of most living organisms.
• Medium for reactions: Provides an environment for biochemical reactions and transport within cells.
• Buffers pH: Helps maintain stable pH through weak acids, bases, and salts.
• Universal solvent: Dissolves many organic and inorganic substances, facilitating biochemical processes.
• Thermoregulation: Absorbs heat to maintain body temperature.
• Source of hydrogen ions: In plants, water provides H⁺ ions for photosynthesis.
• Waste removal: Helps eliminate metabolic wastes and maintain homeostasis.

Water's Active Role as a Biomolecule

• Water is not just a passive solvent but actively participates in biological reactions (e.g., photosynthesis, respiration, hydrolysis).
• Hydrogen bonding gives water unique properties: dynamic bonds constantly break and reform, resulting in high cohesion and unusual physical behaviors (e.g., high heat capacity, density anomaly).
• Water influences the structure of proteins and DNA through hydrophobic and hydrophilic interactions.
• Biological water forms structured layers around biomolecules, affecting their function and stability.
• Water supports enzyme catalysis and molecular binding by stabilizing biomolecules.

Functions of Water in the Human Body

1. Transport Vehicle: Water dissolves nutrients, gases, and wastes, enabling their movement through blood and bodily fluids.
2. Medium for Chemical Reactions: Provides the environment for enzymatic reactions; participates directly in many biochemical processes.
3. Lubricant and Shock Absorber: Present in fluids that protect organs and tissues (e.g., cerebrospinal fluid, synovial fluid, amniotic fluid).
4. Temperature Regulator: High heat capacity stabilizes body temperature. Skin sensors and the hypothalamus regulate heat loss and retention through blood flow, sweating, shivering, and metabolism. Evaporation of sweat cools the body, helping prevent overheating.

Inorganic Biomolecules: Gases, Ions, and Minerals

Essential Biological Gases

Gases are significant for basic cellular processes.

Ions

Ions are required to maintain the osmotic concentration of cellular as well as extracellular fluids.

Minerals (Micro and Macronutrients)

Minerals are nutrients required, especially for the growth of plants, absorbed from the soil. They are classified as macronutrients (required in larger quantity) or micronutrients (required in trace levels). The role of some minerals in cell metabolism is as follows:

Carbohydrates: Structure, Classification, and Function

Basic Composition and Sugar Types

• Carbohydrates are composed of Carbon (C), Hydrogen (H), and Oxygen (O)—often called hydrates of carbon.

Types of Sugars

• Reducing sugars: Sugars that have a free aldehyde or ketone group capable of reducing other compounds (e.g., glucose).
• Non-reducing sugars: Sugars where the free aldehyde/ketone groups are involved in glycosidic bonds and thus “masked” (e.g., sucrose formed by glucose and fructose).

Classification by Functional Group

• Aldoses: Contain an aldehyde group (Examples: Glucose, Ribose, Deoxyribose, Mannose, Galactose)
• Ketoses: Contain a ketone group (Examples: Fructose, Ribulose, Xylulose)

Classification by Number of Monomers

Monosaccharides (Single Sugar Units)

Monosaccharides are single sugar units and are water soluble.

• Trioses (3 carbons): Dihydroxyacetone, Glyceraldehyde
• Tetroses (4 carbons): Threose, Erythrose
• Pentoses (5 carbons): Ribose, Deoxyribose, Xylose, Ribulose, Arabinose
• Hexoses (6 carbons): Glucose (blood sugar/dextrose), Fructose (fruit sugar), Galactose, Mannose
• Heptoses (7 carbons): Sedoheptulose

Oligosaccharides (2–9 monomers)

• Disaccharides: Maltose, Sucrose, Lactose
• Trisaccharides: Raffinose, Pectin, Inulin

Polysaccharides (Many Monomers)

• Homopolymers: Made up of only one type of monosaccharide (Examples: Starch, Hemicellulose, Cellulose, Glycogen)
• Heteropolymers: Made of two or more types of monosaccharides (Examples: Agar, Chitin)

Key Chemical Feature

Monomers are linked by glycosidic bonds during polymerization to form disaccharides, oligosaccharides, and polysaccharides.

Types and Functions of Polysaccharides

• Storage Polysaccharides: Starch and inulin (stored in roots, tubers of plants); Glycogen (in animals and bacteria).
  • Note: Inulin is the smallest polysaccharide; it is not metabolized in the human body, is filtered through the kidney, and is used in kidney testing.
• Structural Polysaccharides: Cellulose, Hemicellulose, Pectin (in plants), Chitin (plant fibers and animal exoskeleton like insects, spiders, crabs, etc.).
  • Chondroitin sulfate: Found in cartilage, tendons, and ligaments.
  • Hyaluronic acid (glucuronic acid + acetyl glucosamine): A cementing substance between animal cells, found in different body fluids (e.g., vitreous humor of the eye, sinusoidal fluid, CSF).
  • Keratan Sulfate: Found in the cornea, skin, cartilage, bone, hair, and nails.
• Mucopolysaccharides: Slimy substances (e.g., Hyaluronic acid).

Industrial and Therapeutic Polysaccharide Applications

• Agar: Used in culture media, medicine, capsules, and chromatography.
• Algin: Used in ice creams and cosmetics.
• Carrageenin: Used as an emulsifier and clearing agent (e.g., fruit juice).
• Funori: Used as an adhesive in hair curling.
• Heparin: Used in blood banks as an anticoagulant.
• Husk of Plantago ovata: Used as a purgative/laxative.
• Aloegel: Used for inflammation relief, and in hand lotion, shampoo, hair conditioner, and sunscreen lotion.

Carbohydrate Engineering and Applications

Carbohydrates are vital biomolecules involved in structural, functional, and metabolic processes essential to life. They play key roles in cell interactions, genetic material organization, structural support, energy storage, immune signaling, and food texture modification. Carbohydrates often form complex networks and have useful properties like sweetness, solubility, and coating abilities, making them valuable in therapeutic and industrial applications.

Carbohydrate polymers (mainly polysaccharides) are long chains of sugar units linked by oxygen bridges. They include storage polymers (starch, dextrins), structural polymers (cellulose, chitin), and protective polymers (hyaluronic acid, gums). These natural polymers are abundant, renewable, cost-effective, and environmentally friendly alternatives to synthetic polymers.

Recent advances in carbohydrate engineering enable chemical modification of these polymers, leading to new materials, drugs, vaccines, and industrial applications such as drug delivery, corrosion resistance, catalysis, and eco-friendly energy solutions. Carbohydrate polymers are poised to drive sustainable innovation across many fields.

Biomedical Applications of Carbohydrates

Carbohydrates are widely used in biomedical fields such as drug delivery, imaging, tissue engineering, and wound healing due to their biocompatibility, biodegradability, hydrophilicity, and non-toxicity.

• Tissue Engineering: Carbohydrate-based scaffolds (oligosaccharides and polysaccharides), especially those mimicking the extracellular matrix (ECM), support stem cell growth and tissue regeneration by providing a favorable environment for cell therapy.
• Drug Delivery: Carbohydrate polymers like hyaluronic acid, chitosan, dextran, alginates, gellan, chitin, and pullulans serve as carriers for controlled and targeted drug release via hydrogels, nanoparticles, microspheres, and gels. They enhance drug stability, targeting, and sustained release, and some (e.g., gellan) act as adhesives to retain drugs at specific sites.
• Nanomaterials: Carbohydrate-based nanoparticles and nanogels are used in targeted drug delivery and bioimaging. Their ability to target specific cell receptors and combine with inorganic nanoparticles reduces toxicity and improves therapeutic efficacy.
• Wound Healing: Hyaluronic acid is also employed in medical wound dressings for improved healing.

Agricultural Applications

Carbohydrate-based biopolymeric nanoparticles improve crop yields by protecting plants from pathogenic fungi through inhibiting spore germination and stimulating plant immune responses. They also serve as cost-effective carriers for controlled-release agrochemicals, offering an eco-friendly alternative to conventional fungicides, crucial for feeding a growing global population.

Industrial Applications

• Bio-based Packaging: Carbohydrate polymers (starch, cellulose, polylactic acid) blended with polyhydroxyalkanoates (PHA) enhance biodegradable packaging by improving mechanical properties and reducing costs.
• Synthetic Carbohydrate Receptors: Engineered receptors that recognize carbohydrates show promise for medical applications like glucose sensing and antiviral/antibiotic functions.
• Corrosion Resistance: Carbohydrate polymers act as eco-friendly, cost-effective corrosion inhibitors by binding corrosive molecules through their cyclic structures, protecting metals from environmental damage.
• Catalysis: Carbohydrate polymers (starch, cellulose, chitosan) serve as solid supports in heterogeneous catalysis due to their tunable properties, low toxicity, and thermal stability, facilitating efficient chemical reactions.

Fuel Cells Applications

Carbohydrate polymers like chitosan, starch, cellulose, and glycogen are explored as eco-friendly, low-cost alternatives for polymer electrolytes in fuel cells. Chitosan, in particular, is valued for its modifiable properties that suit proton-exchange membranes by reducing methanol permeability and enhancing hydrophobicity. Cellulose also shows potential as a sustainable fuel source in aqueous or liquid form.

Future Outlook for Carbohydrate Polymers

With growing emphasis on renewable and sustainable materials, carbohydrate polymers are expected to see expanded use, especially in fuel cells and drug delivery. Their abundance and biocompatibility promise wider applications in medical and healthcare fields in the near future.

Lipids: Energy Storage and Membrane Structure

Lipids are non-polar organic compounds mainly composed of carbon and hydrogen, with minimal oxygen, making them insoluble in water. They serve as key components of cell membranes and are energy-dense molecules, providing significantly more energy than carbohydrates (the text states six times more energy). Lipids include fatty acids, fats & oils, phospholipids, and steroids.

Types of Lipids

1. Simple Lipids: Neutral fats or waxes, which hydrolyze into fatty acids and glycerol (e.g., tripalmitin).
2. Compound Lipids: Include phospholipids (e.g., cephalin, lecithin), glycolipids (e.g., cerebrosides), lipoproteins, cutin, suberin, and chromolipids (carotenoids).
3. Derived Lipids: Formed by hydrolysis of simple/compound lipids, such as fatty acids, steroids, prostaglandins, and terpenes.

Key Components of Lipids

• Fatty Acids: Long hydrocarbon chains with a hydrophilic carboxyl group.
• Fats & Oils: Energy reserves; saturated fats (solid, no double bonds) are typical in animals, unsaturated fats (liquid, with double bonds) in plants.
• Phospholipids: Major membrane components with phosphate and nitrogen groups.
• Steroids: Include cholesterol, essential for membranes, hormone precursors, vitamin D synthesis, and cell signaling.

Properties of Lipids

• Insoluble in water, soluble in organic solvents.
• Low density (float on water).
• Undergo rancidity via oxidation, producing foul odors.

Functions of Lipids

• Energy Storage: Dense energy reserves in plants (oilseeds) and animals (adipocytes).
• Structural Role: Components of membranes (phospholipids, glycolipids, sterols).
• Biosynthesis: Precursors for steroids, hormones, and vitamin D.
• Insulation & Protection: Thermal/electrical insulation, shock absorption, and waterproofing (waxes).
• Solvents: Carry fat-soluble vitamins (A, D, E, K).

Lipid Engineering and Applications

Lipid Engineering is a field focusing on modifying lipid production and fatty acid composition to improve industrial and medical applications, including healthier fats (e.g., enriched olive oil), biofuels, and pharmaceuticals. This offers sustainable alternatives and advances in personalized medicine.

Q&A on Lipid Engineering

What are the potential benefits of lipid engineering in food production?

Lipid engineering in food production can enhance nutritional profiles by enriching foods with healthy fats, improve the taste and texture of food products, increase the stability and shelf-life of foods, and facilitate the production of functional foods that support health and prevent disease.

How does lipid engineering impact the nutritional value of foods?

Lipid engineering enhances the nutritional value of foods by modifying the fatty acid composition, improving energy density, and introducing beneficial lipids like omega-3 and omega-6 fatty acids. It can also reduce unhealthy trans fats, leading to improved cardiovascular health and better overall nutrient profiles.

What are the potential risks or challenges associated with lipid engineering in the food industry?

Potential risks or challenges of lipid engineering in the food industry include the possibility of unintended health effects, ethical concerns over genetically modified organisms, regulatory hurdles, and public resistance to modified food products due to concerns over safety and ecological implications.

How does lipid engineering affect the sustainability of food systems?

Lipid engineering enhances the sustainability of food systems by improving the nutritional profile of food, increasing crop yields of oil-producing plants, and reducing reliance on environmentally harmful agricultural practices. It enables the production of healthier and more efficient lipid sources, potentially lowering resource use and environmental impact.

What role does lipid engineering play in developing plant-based meat alternatives?

Lipid engineering is crucial in developing plant-based meat alternatives by enhancing the texture, flavor, and nutritional profile. It focuses on creating lipid structures that mimic animal fat, improving mouthfeel and taste. Additionally, engineered lipids can help achieve desired nutritional compositions, such as healthier fat profiles in these products.

Biofuels and Industrial Applications

Biofuels: Lipid engineering can create renewable energy sources by changing lipid pathways in microorganisms.

Industrial Applications: Lipids and plant oils can be used in many industrial applications, such as:

• Coatings and polymers
• Printing inks
• Lubricants
• Cosmetics and pharmaceuticals
• Leather processing
• Surfactants
• Solvents
• Hydraulic fluids
• Pesticide and herbicide adjuvants
• Glycerin

Other areas of lipid engineering include microbial production of functional lipids, metabolic engineering of microorganisms, elucidation of physiological functions of rare lipids, lipid-related enzyme engineering, and lipid analysis techniques.

Proteins: Structure, Classification, and Function

Proteins make up more than 50% of the dry mass of animals and bacteria and perform important functions in living organisms. They contain the elements carbon, oxygen, hydrogen, nitrogen, and usually sulfur, which form the protein monomer: the amino acid (AA). All organisms contain 20 common amino acids as biological molecules.

Amino Acid Classification

• Essential Amino Acids: Cannot be synthesized by animals, so they must be obtained through diet. Humans require 8 essential amino acids; other animals require 7.
• Non-essential Amino Acids: Can be synthesized by animals, so they may not be required in the diet.

Each amino acid (AA) has a carboxyl group (-COOH), an amino group (-NH₂), and a hydrogen atom bonded to a central carbon atom. The sequence of amino acids (linked by peptide bonds) determines the overall shape and properties of proteins. Based on the number of amino acids in a chain, they are classified as:

• Oligopeptides (1–10 AA)
• Polypeptides (11–50 AA)
• Proteins (>50 AA)

Structural Organization of Proteins

Proteins are classified into four levels of structural organization:

Primary Structure

A simple, two-dimensional chain of amino acids linked by peptide (covalent) bonds (e.g., Insulin).

Secondary Structure

Local folding where various functional groups exposed on the outer surface interact via hydrogen bonds.

• Alpha (α)-helix: A coiled spiral stabilized by hydrogen bonds between amino and carboxyl groups four residues apart (e.g., keratin in hair, fur, claws, hooves).
• Beta (β)-pleated sheet: Parallel or anti-parallel strands forming hydrogen bonds laterally (e.g., β-keratin of feathers, silk fibroin).
• Collagen helix: Three α-helices coiled around one another.

Tertiary Structure

The overall 3D shape formed by the twisting of the secondary structure. It involves additional bonds between functional groups, including weak covalent and high-energy disulfide bonds (e.g., Myoglobin).

Quaternary Structure

Formed by the association of two or more polypeptide chains and have specific orientation.

Classification of Proteins

By Structure (Shape)

• Fibrous: Collagen fibers, keratin, elastin, fibrin, fibroin, actin, myosin, involved in blood clotting.
• Globular: Glutelin, protamine, globulin, albumin, glutenin, oryzenin.
• Intermediate: Myosin, fibrinogen.

By Chemical Nature

• Simple Proteins: Contain only amino acids (e.g., Albumin, globulin, protamine, prolamine (corn, wheat), histone (corn, wheat), glutelin (glutenin), keratin).
• Conjugated Proteins: Protein combined with a non-protein component (prosthetic group). Examples include:
  • Nucleoprotein (with nucleic acid)
  • Chromoprotein (e.g., Hemoglobin, cytochrome)
  • Metalloprotein (with metals like Zn, Fe)
  • Lipoprotein, Glycoprotein, etc.

Properties of Proteins

• Number: Thousands of proteins exist, varying according to the length, number, and types of polypeptides.
• Specificity: High specificity within an individual, but shared with related species or groups.
• Molecular Weight: Ranges widely, from ACTH (4,500 daltons) to Pyruvate Dehydrogenase (4,600,000 daltons).
• Solubility: Some are insoluble due to large size; many form colloidal solutions with water.
• Amphoteric Nature: Show both acidic and basic properties.
• Electrical Reaction: Defined by the isoelectric point (the pH at which the protein is neutral). Curdling of milk occurs at the acidic isoelectric point (pH 4.7).
• Denaturation: Permanent or temporary loss of three-dimensional structure caused by UV light, heat, strong acids/alkalis, or high salt concentration. Within limits, renaturation can occur.

Detailed Look at Protein Folding

The following structures detail the folding process:

• Primary Structure: A protein is a chain of amino acids linked by peptide bonds, like beads on a string. Each amino acid has a central carbon bonded to an amino group, carboxyl group, hydrogen atom, and a unique side chain (R-group). Proline is unique with a ring structure. The sequence of amino acids determines the protein's identity.
• Secondary Structure: Involves local folding into two common shapes:
  • Alpha-helix: A coiled spiral stabilized by hydrogen bonds between amino and carboxyl groups four residues apart; found in hemoglobin and intermediate filaments. Amino acids like methionine and lysine favor this.
  • Beta-pleated sheet: Parallel or anti-parallel strands forming hydrogen bonds laterally; found in fatty acid transport proteins and antibodies. Amino acids like valine and tryptophan favor this. Kinks in beta-sheets often indicate proline presence.
• Tertiary Structure: The overall 3D shape formed by folding of secondary structures. Driven mainly by hydrophobic (water-fearing) amino acids folding inward and hydrophilic (water-loving) amino acids folding outward.

The quaternary structure involves two or more polypeptide chains associating into a single, functional protein held together by non-covalent bonds and sometimes disulfide bonds. It is essential for the function of complex proteins like hemoglobin and antibodies.

Secondary structures also relate to functional proteins (e.g., immunoglobulins from bone marrow; albumin from liver) and acute phase reactants (produced during inflammation, e.g., transferrin).

Thermodynamics in Biological Systems

The First Law of Thermodynamics in Biology

• Law Statement: Energy cannot be created or destroyed—only converted from one form to another.
• Biological Relevance:
  • In photosynthesis, light energy is used to convert CO₂ and H₂O into glucose and O₂:

    6 CO₂ + 6 H₂O + light → C₆H₁₂O₆ + 6 O₂

  • Non-photosynthetic organisms oxidize glucose to produce CO₂, H₂O, and energy:

    C₆H₁₂O₆ + 6 O₂ → 6 CO₂ + 6 H₂O + energy

• Macromolecule Synthesis (e.g., DNA, proteins) requires energy to maintain molecular order.
• Mathematical Formulation:

  ΔE = q - w (Change in internal energy = heat absorbed - work done)

The Second Law of Thermodynamics

• Law Statement: In any spontaneous process, the total entropy (disorder) of the universe increases.
• Entropy (S): Measure of system randomness.
  • If ΔS > 0, there is more disorder, indicating a spontaneous process.
• Implications for Biology:
  • Cells require free energy (ΔG) to create order from disorder (e.g., protein synthesis).
  • ΔG = ΔH - TΔS
    • If ΔG < 0, the reaction is exergonic (spontaneous).
    • If ΔG > 0, the reaction is endergonic (non-spontaneous).
    • If ΔG = 0, the system is at equilibrium.

Living Systems and Thermodynamics

Living organisms are:

1. Open systems: They exchange both matter and energy with their surroundings.
2. Isothermal systems: They maintain a constant internal temperature and cannot use heat flow directly for work.
3. In steady state: They maintain constant internal conditions through continuous energy use, operating far from equilibrium.
4. Isothermal chemical engines: They use free energy for biosynthesis, transport, muscle contraction, etc.
5. Non-equilibrium systems: They can regulate and perform work.

Organisms do not violate thermodynamic laws: They increase entropy in the environment (by releasing heat and waste) while maintaining internal order. Thus, they minimize but do not eliminate entropy production.

Free Energy and Equilibrium

• Standard Free Energy Change:

  ΔG° = -RT ln K′eq (Relates free energy to the equilibrium constant.)

  • At equilibrium: ΔG = 0
• Actual ΔG depends on concentrations of reactants/products:

  ΔG = ΔG° + RT ln([C][D]/[A][B])

Application: Mimicking Photosynthesis for Solar Cells

By Park Sae-jin

Researchers are developing efficient solar cell technology by mimicking plants' photosynthesis process. By inducing an ideal electron flow process called vectorial transfer, South Korean researchers were able to develop a solar cell manufacturing technique that can produce cells with up to 60% more electron transfer efficiency than conventional cells. The new technique allows photovoltaic cells to control electron flow in one desired direction to reduce the loss of electrons during power generation.

Conventional photosensitizers used in photovoltaic cells have strong electronic coupling characteristics, which lose a lot of electrons when transferred between molecules because of the rapid recombination of electrons and electron holes. Electron holes are positions that lack an electron in an atom or atomic lattice. Natural photosystems, such as those used by plants for photosynthesis, utilize vectorial transfer to control the direction of electron flow and prevent the recombination of electrons and holes. Plants show about 100% efficiency in the transfer of electrons.

The Ulsan National Institute of Science and Technology (UNIST) said in a statement that a joint team involving researchers from UNIST and Japan's Shinshu University developed a technique to create more efficient solar cells using a specially designed dye that has both strong and weak electronic coupling characteristics to minimize the electron recombination phenomenon.

Solar cells using the dye showed a maximum photovoltaic efficiency of 10.8%, which is about 60% more efficient than conventional cells. The rate of recombination was about 12.5% compared to ordinary photovoltaic cells. "The molecular design strategy developed in this study can be applied not only to solar cells but also to various fields such as artificial photosynthesis and photocatalysts," UNIST researcher Kwon Tae-hyuk was quoted as saying.