Comprehensive Biochemistry Study Notes on Lipids

General Characteristics and Classification of Lipids

• Definition of Lipids:

  • Biomolecules of an organic nature with highly varied chemical composition.
  • Composed predominantly of carbon and hydrogen.

• General Physical and Chemical Properties:

  • Tactile and Optical Qualities: Exhibit a greasy sheen and are distinctly unctuous (oily) to the touch.
  • Solubility: Completely insoluble in water, but soluble in nonpolar organic solvents such as chloroform and acetone.
  • Density: Less dense than water, causing them to float on aqueous surfaces.
  • Thermal Conductivity: Poor conductors of heat, functioning effectively as thermal barriers.
  • Amphipathic Character: Display amphipathic properties, possessing both a hydrophilic region (water-soluble) and a hydrophobic region (water-repelling).

• Primary Classification:

  • Saponifiable Lipids (Lípidos Saponificables):
  • Contain fatty acids within their molecular structure.
  • Undergo hydrolysis to yield free fatty acids and form soaps in alkaline conditions.
  • Simple Saponifiable Lipids: Composed solely of fatty acids and an alcohol. Subdivided into acylglycerols (fats) and waxes.
  • Complex Saponifiable Lipids: Contain fatty acids, an alcohol, and additional chemical moieties (such as phosphoric acid or carbohydrate units). Subdivided into phospholipids and glycolipids.
  • Unsaponifiable Lipids (Lípidos Insaponificables):
  • Lack fatty acids entirely within their structure.
  • Incapable of undergoing saponification to form soaps.
  • Include terpenes (isoprenoids), steroids, and eicosanoids.

Fatty Acid Structure, Properties, and Reactions

• Molecular Structure:

  • Unbranched, linear hydrocarbon chains ending with an acidic carboxylic group ($-\text{COOH}$) at one terminal.
  • Characterized by an even number of carbon atoms.

• Classification of Fatty Acids:

  • Saturated Fatty Acids (Ácidos Grasos Saturados):
  • Devoid of carbon-carbon double bonds along the hydrocarbon chain.
  • Pack closely together and exist as solids at room temperature.
  • Typical of animal fats.
  • Unsaturated Fatty Acids (Ácidos Grasos Insaturados):
  • Contain one or more double bonds along the chain.
  • Liquid at room temperature due to bends in the chain preventing dense packing.
  • Monounsaturated: Contain a single double bond (e.g., oleic acid / ácido oleico).
  • Polyunsaturated: Contain two or more double bonds (e.g., linoleic acid / ácido linoleico).
  • Double bonds introduce conformational rigidity into the hydrocarbon backbone.
  • Exist as cis-trans geometric isomers.

• Geometric Isomerism:

  • Cis Configuration: Hydrogen atoms bonded to the double-bonded carbons are situated on the same side of the chain, inducing a distinct bend or kink in the structure.
  • Trans Configuration: Hydrogen atoms bonded to the double-bonded carbons are situated on opposite sides of the chain, maintaining an extended, linear structure similar to saturated chains.

• Principal Polyunsaturated Fatty Acids:

  • Omega-3 ($\omega-3$) Family:
  • EPA (Eicosapentaenoic Acid / Eicosa Pentanoic Acid): Shorthand notation $20:5\,\Delta 5, 8, 11, 14, 17$, representing a $20$-carbon chain with $5$ double bonds at carbon positions $5$, $8$, $11$, $14$, and $17$.
  • DHA (Docosahexaenoic Acid / Docosa Hexanoic Acid): Shorthand notation $22:6\,\Delta 4, 7, 10, 13, 16, 19$, representing a $22$-carbon chain with $6$ double bonds located at positions $4$, $7$, $10$, $13$, $16$, and $19$; abundantly sourced from fish (peces).
  • Omega-6 ($\omega-6$) Family:
  • Linoleic Acid (Ácido Linoleico): Shorthand notation $18:2\,\Delta 9, 12$, designating an $18$-carbon chain containing $2$ double bonds at positions $9$ and $12$.
  • Arachidonic Acid (Ácido Araquidónico): Shorthand notation $20:4\,\Delta 5, 8, 11, 14$, designating a $20$-carbon chain with $4$ double bonds at positions $5$, $8$, $11$, and $14$; found prominently in animal phospholipids (fosfolípidos animales).

• Physical Properties of Fatty Acids:

  • Melting Point (Punto de Fusión):
  • Governed directly by the magnitude of intermolecular Van der Waals attractions between carbon chains.
  • Increases with chain length: longer hydrocarbon chains possess greater contact surface area, strengthening Van der Waals interactions.
  • Increases with degree of saturation: saturated chains align tightly in parallel, maximizing Van der Waals forces and elevating melting temperatures.
  • Decreases with unsaturation: double bonds (specifically cis) create rigid kinks that hinder close molecular packing, significantly weakening Van der Waals forces and lowering melting points.
  • Solubility and Behavior in Aqueous Media:
  • Fatty acids are amphipathic molecules containing a polar, hydrophilic carboxyl head and an apolar, hydrophobic hydrocarbon tail.
  • In aqueous environments, the polar heads interact with water molecules by establishing hydrogen bonds.
  • The apolar tails flee water molecules, clustering together via hydrophobic interactions and Van der Waals forces.

• Chemical Properties of Fatty Acids:

  • Driven by the reactivity of the terminal carboxyl group ($-\text{COOH}$):
  • Esterification Reaction (Reacción de Esterificación):
  • A condensation reaction between a fatty acid and an alcohol.
  • Results in the formation of a covalent ester bond and the liberation of one molecule of water ($H_2O$):       $\text{Fatty Acid} + \text{Alcohol} \rightarrow \text{Ester} + H_2O$
  • Saponification Reaction (Reacción de Saponificación):
  • A base-catalyzed hydrolysis reaction between a fatty acid (or an esterified fatty acid) and a strong base (e.g., $\text{NaOH}$ or $\text{KOH}$.
  • Yields an alkaline salt of the fatty acid—known as soap (jabón)—along with water or an alcohol:       $\text{Fatty Acid} + \text{Strong Base} \rightarrow \text{Salt (Soap)} + H_2O$

Simple Saponifiable Lipids: Acylglycerols and Waxes

• Definition and Overview:

  • Lipids composed exclusively of fatty acids linked via ester bonds to an alcohol or an amino alcohol.
  • Can be cleaved by hydrolysis to release their constituent free fatty acids.
  • Classified into fats (acylglycerols) and waxes.

• Fats (Acylglycerols / Grasas):

  • Vegetable Origin Fats: Composed primarily of unsaturated fatty acids; remain liquid at ambient room temperature (e.g., olive oil / aceite de oliva).
  • Animal Origin Fats: Composed primarily of saturated fatty acids; remain solid or semisolid at ambient room temperature (e.g., butter / mantequilla, bacon fat / tocino).
  • Energetic Functions of Fats:
  • Constitute the primary long-term energetic reserve in both plant and animal kingdoms.
  • Stored intracellularly in vacuoles within plant tissues and in specialized adipocytes within animal adipose tissue.
  • Yield significantly higher energetic output upon oxidation than carbohydrates (glúcidos).
  • Stored in a dehydrated state, occupying far less volume and carrying substantially less mass per unit of stored energy than hydrated carbohydrates.
  • Physiological Survival Values:
  • Thermal Insulation: Accumulated beneath the skin (subcutaneous fat) in animals inhabiting cold environments, preventing internal heat loss.
  • Mechanical Insulation: Form protective cushions surrounding vital visceral organs (e.g., heart and kidneys), shielding them from physical impacts and trauma.

• Waxes (Ceras):

  • Chemical Nature: Esters formed through the condensation of a long-chain fatty acid with a high-molecular-weight, long-chain monohydric alcohol.
  • Properties and Biological Roles:
  • Strongly hydrophobic and waterproof.
  • Prevent desiccation by forming protective outer coatings on plant aerial surfaces (leaves and fruits).
  • Protect anatomical cavities from water and pathogen infiltration, such as lining the external auditory canal.
  • Notable Examples:
  • Lanolin (lanolina), extracted from sheep wool.
  • Spermaceti oil (aceite de espermaceti), harvested from the cranial cavities of sperm whales (cachalote / cetaceans).

Complex Saponifiable Lipids: Phospholipids and Glycolipids

• Molecular Overview:

  • Esters containing fatty acids attached to an alcohol backbone (glycerol or sphingosine), joined to additional non-lipid moieties such as phosphoric acid or carbohydrate molecules.
  • Markedly amphipathic, forming the structural foundation of biological membrane bilayers.

• Phospholipids (Fosfolípidos):

  • Characterized by the presence of an esterified orthophosphoric acid group.
  • Glycerophospholipids (Glicerofosfolípidos):
  • Triesters formed on a glycerol backbone.
  • Consist of two fatty acids esterified to the first two hydroxyl carbons, while the third hydroxyl group is esterified to a phosphoric acid.
  • The phosphoric acid is further esterified to an amino alcohol (e.g., choline, ethanolamine).
  • Sphingophospholipids (Esfingofosfolípidos):
  • Formed from an amino alcohol with a long hydrocarbon chain (sphingosine).
  • A fatty acid is attached to the backbone via an amide bond through the amino group.
  • The primary hydroxyl group is esterified to a phosphate group, which in turn bonds to a second alcohol (specifically choline or ethanolamine).

• Glycolipids (Glucolípidos):

  • Complex lipids containing carbohydrate residues; completely devoid of phosphate groups.
  • Glyceroglycolipids (Gliceroglucolípidos):
  • Formed by glycerol linked to two fatty acid chains and a monosaccharide carbohydrate unit.
  • Predominantly distributed across the biological membranes of bacteria and plant cells.
  • Sphingoglycolipids (Esfingoglucolípidos / Esfingoglicolípidos):
  • Contain a ceramide core (sphingosine linked via an amide bond to a fatty acid) attached to a carbohydrate head group.
  • Cerebrosides (Cerebrósidos): Formed by a ceramide attached to a single monosaccharide unit.
  • Gangliosides (Gangliósidos): Formed by a ceramide linked to a branched oligosaccharide chain; localized prominently on the extracellular outer leaflet of neuronal membranes.

Unsaponifiable Lipids: Terpenes, Steroids, and Eicosanoids

• Terpenes (Isoprenoids / Terpenos):

  • Polymeric derivatives formed from repeating units of isoprene ($2\text{-methyl-1,3-butadiene}$, $5\text{C}$).
  • Highly hydrophobic compounds completely insoluble in water.
  • Biological Distribution and Examples:
  • Pigments: Carotenoids including carotenes, xanthophylls, and lycopenes.
  • Plant Essential Oils and Essences: Volatile compounds providing fragrance and defense, including menthol and eucalyptus (eucalipto).
  • Lipid-Soluble Vitamins: Vitamins A, E, and K.

• Steroids (Esteroides):

  • Structurally derived from sterane (esterano, cyclopentanoperhydrophenanthrene), a fused four-ring hydrocarbon core that provides structural rigidity and profound hydrophobicity.
  • Cholesterol (Colesterol):
  • Critical structural component intercalated into eukaryotic cellular membranes, modulating fluidity.
  • Acts as the metabolic precursor from which all other steroidal compounds are biosynthesized.
  • Bile Acids (Ácidos Biliares):
  • Synthesized inside the liver via cholesterol transformation.
  • Emulsify dietary fats in the intestinal lumen, dramatically increasing surface area to favor enzymatic digestion.
  • Vitamin D:
  • Regulates systemic calcium metabolism and enhances its intestinal absorption.
  • Steroid Hormones (Hormonas Esteroideas):
  • Sex Hormones: Progesterone and testosterone, regulating gametogenesis and secondary sexual traits.
  • Adrenocortical Hormones: Produced by the adrenal cortex, including cortisol (regulates metabolism and stress response) and hormones governing electrolyte balance and water absorption.

• Eicosanoids (Eicosanoides):

  • Bioactive lipid signaling molecules biosynthesized from arachidonic acid, an omega-6 polyunsaturated fatty acid containing $20$ carbon atoms ($20\text{C}$).
  • Prostaglandins (Prostaglandinas): Mediate vascular tone, inflammatory pathways, pain, and smooth muscle contraction.
  • Thromboxanes (Tromboxanos): Synthesized in blood platelets (plaquetas); promote platelet aggregation and vasoconstriction during clot formation.
  • Leukotrienes (Leucotrienos): Produced by white blood cells (glóbulos blancos); mediate allergic responses, bronchoconstriction, and inflammatory recruitment.

Physiological Functions of Lipids and Lipoprotein Transport

• Unified Biological Functions of Lipids:

  • 1. Energetic Function (Función Energética): Efficient primary long-term cellular fuel storage providing higher ATP yield per gram upon complete combustion compared to sugars.
  • 2. Structural Function (Función Estructural): Assembly of lipid bilayers (phospholipids, glycolipids, cholesterol) defining cell boundaries and intracellular organelle membranes.
  • 3. Covering and Protection (Recubrimiento y Protección): Waterproof wax coatings on epidermal tissues of leaves, fruits, and skin preventing mechanical wear and desiccation.
  • 4. Thermal Insulation (Aislante Térmico): Subcutaneous fat tissue deposits reducing heat conductance to protect homeotherms against cold environments.
  • 5. Biocatalysts and Regulators (Biocatalizadores): Signaling hormones (steroids, eicosanoids) and vitamin cofactors (vitamins A, D, E, K) that control metabolic reactions and physiology.

• Lipoproteins (Lipoproteínas):

  • Spherical macromolecular complexes containing a hydrophobic lipid core and an amphipathic surface monolayer of proteins and phospholipids, rendering insoluble lipids soluble in water and circulating blood.
  • Chylomicrons (Quilomicrones):
  • Lipoproteins possessing the largest diameter and lowest density.
  • Transport exogenous dietary lipids from the intestines to peripheral tissues.
  • Low-Density Lipoproteins (LDL / Lipoproteínas de Baja Densidad):
  • Often termed "bad cholesterol."
  • Responsible for transporting synthesized cholesterol away from the liver toward peripheral peripheral tissues.
  • High-Density Lipoproteins (HDL / Lipoproteínas de Alta Densidad):
  • Responsible for reverse cholesterol transport.
  • Collect excess cholesterol from body tissues and vascular walls, carrying it back to the liver for metabolic processing and destruction.