Lipids and Cell Membranes lect 8

Carbohydrates Apology

• Apology for being disparaging about carbohydrates in the previous lecture.

• Emphasis on the importance of carbohydrates.

• Reference to an old video about converting toilet paper into alcohol.

  • Based on the idea that toilet paper is made of cellulose.

  • Cellulose is found in plants and used to make various products.

  • Homemade alcohol production from spirits is illegal.

  • The video became useful during COVID for making hand sanitizers.

  • The lecturer has only made alcohol from apples.

  • The video is 15-30 minutes long and may be useful for diversion during revision.

Introduction to Lipids

• Lipids are the final biomolecule to be discussed in this section of the course.

• Next week's topic: cellular mechanisms and metabolism, followed by drugs.

• Lipids are defined as everything that isn't protein, peptide, or carbohydrate.

• Lipids include fats, waxes, steroids, many vitamins, diglycerides, glycerides, and phospholipids.

• Examples to be discussed: steroids, fatty acids, and phospholipids.

Simple Lipids: Fatty Acids

• Simplest lipids: long hydrocarbon chains with a carboxylic acid head group.

• Hydrophobic chains with a hydrophilic head group.

• The head group is generally ionized in solution.

• Amphiphilic nature allows for self-assembly.

• The acid group enables attachment to other molecules like amino acids and carbohydrates; acts like a "gluey end".

• Palmitic acid: a large component of human fat.

• Fatty acids exist mostly in the form of esters.

• Chain length typically 18-20 carbons long.

• Key labels: saturated and unsaturated.

  • Saturated: no double bonds.

  • Unsaturated: double bonds.

• Generally, saturated fatty acids are considered bad, and unsaturated (non-trans) are considered good for dietary health.

• Saturated fats are typically found in butter, unsaturated in margarine.

• Solid fats vs liquid or soft fats are determined by the presence of double bonds influencing chain packing.

• Examples of saturated fatty acids: acetic acid, loric acid, stearic acid.

• Unsaturated fatty acids can be cis or trans; can have multiple double bonds.

• Examples of unsaturated fatty acids: oleic acid, arachidonic acid.

• Common names are typically used for acids in biology rather than chemical names.

• Monounsaturated: one double bond.

• Polyunsaturated: multiple double bonds.

Fatty Acids as Acids

• Fatty acids are acidic (Bronsted acids).

• Exist in equilibrium, giving up hydrogen.

• pKa typically around 4-5.

• Body acidity is around 6-7, so fatty acids in the body are mostly ionized (minus form), making them chemically reactive.

• This contributes to their amphiphilic nature.

• pKa of 4 is not super acidic; it's like vinegar (acetic acid).

• Not strong enough to destroy evidence like in "Breaking Bad".

• pKa of 4-5 is acidic enough to be ionized but not dangerously acidic.

Glycerides and Phospholipids

• Most fatty acids exist in the form of esters.

• Glycerides are compound esters of glycerol and fatty acids.

• Industrially important for isolating fatty acids and glycerol.

• Monoglyceride: one ester group.

• Diglyceride: two ester groups.

• Triglyceride: three ester groups.

• Chain lengths in glycerides vary; can be saturated, unsaturated, polyunsaturated.

• Glycerides are reservoirs of fat in the body.

• Phospholipids are more complex; glycerol with two ester groups and a phosphate on the upper position.

• Various molecules can attach to the phosphate: ethanolamine, choline, serine, inositol.

  • Ethanolamine and choline are most common.

  • Ethanolamine is two carbons with a nitrogen.

Sphingolipids

• Sphingosine: no ester group, officially linked.

• Ceramide, sphingomyelin (phosphate group added).

• Key difference: amide bond instead of ester bond.

• Direct carbon bond up to the phosphate.

• Sphingolipids.

Steroids

• Steroids are considered lipids with a cyclic skeleton.

  • Contain cyclohexanes and cyclopentanes.

• Stereochemistry is important; defines shape.

• Limited flexibility due to cyclic structure, leading to defined shapes.

• Shapes help interact with enzymes and receptors.

• Steroids as hormones: regulate physiological activities and homeostasis; act as chemical messengers.

• Cholesterol: important for cellular structure.

• Examples: Testosterone, hydrocortisone, cholesterol.

• Testosterone: Men tend to have more than women.

• Hydrocortisone cream: used for eczema and to reduce inflammation and allergies, insect bites.

• Structure of steroids: 6-6-6-5 ring structure despite different functions.

Membrane Lipids

• Cell membranes are mainly made of lipids.

• Long hydrocarbon tails, glycerol group attached to the phosphate, phosphate attached to various molecules like choline.

• Typically, one chain has a double bond, creating a kink.

• C18 hydrocarbon (octadecane): a solid or wax at room temperature.

• Body temperature is slightly above room temperature.

• Solid fats are undesirable in the body; oily or waxy fats are preferred.

• Double bonds inhibit solidification by preventing chains from co-crystallizing.

• Chains can be unsaturated with mismatched lengths to prevent solidification.

• Ether phosphate linkages and ester-forming phosphate linkages.

• Lipids are amphiphilic: hydrophilic heads, hydrophobic tails.

• In a water environment, phosphate groups (charged) interact with water, leading to self-assembly.

• Two alkyl chains force the formation of a bilayer membrane instead of small cells.

Lipid Bilayer and Drug Delivery

• Hydrophobic chains assemble to avoid water.

• This is the most thermodynamically stable arrangement in water.

• Proteins and carbohydrates help hold the membrane together.

• Lipid bilayer is fluid and relatively impermeable.

• Ions (positive or negative) have difficulty traversing the hydrophobic layer.

• Nonpolar molecules can get through more easily but face issues getting into the water.

• Key problem: getting drugs through the membrane or into water.

• Cell membrane is a focus of drug studies.

• Protein molecules span the lipid bilayer, acting as ion channels, receptors, and transporters.

Membrane Fluidity and Components

• All components within the lipid bilayer are mobile.

• Lateral diffusion, flip-flop, rotation, and bending occur.

• Membrane fluidity is key.

• Membranes can fuse and reproduce.

• Cell's plasma membrane: flexible and fluid.

• Cholesterol: influences membrane fluidity; more cholesterol decreases fluidity.

• Different cells have different membrane fluidity needs.

• Cell membranes differ on the outside from the inside.

• Glycolipids and glycoproteins: carbohydrates attached to lipids or proteins.

• Outside of the cell has phosphorus groups and proteins.

Carbohydrates Apology

• Apology for being disparaging about carbohydrates in the previous lecture.

• Emphasis on the importance of carbohydrates, highlighting their crucial role in energy production and cellular function.

• Reference to an old video about converting toilet paper into alcohol.

  • Based on the idea that toilet paper is made of cellulose.

  • Cellulose is a complex carbohydrate found in the cell walls of plants, making it a source for producing alcohol through fermentation.

  • Homemade alcohol production from spirits is illegal due to safety concerns and regulations.

  • The video became useful during COVID for making hand sanitizers, demonstrating an alternative application of alcohol produced from cellulose.

  • The lecturer has only made alcohol from apples, emphasizing traditional methods.

  • The video is 15-30 minutes long and may be useful for diversion during revision, offering a brief educational break.

Introduction to Lipids

• Lipids are the final biomolecule to be discussed in this section of the course.

• Next week's topic: cellular mechanisms and metabolism, followed by drugs.

• Lipids are defined as everything that isn't protein, peptide, or carbohydrate, encompassing a wide range of molecules with diverse functions.

• Lipids include fats, waxes, steroids, many vitamins, diglycerides, glycerides, and phospholipids, showcasing their structural and functional variety.

• Examples to be discussed: steroids, fatty acids, and phospholipids, providing specific instances of lipid types.

Simple Lipids: Fatty Acids

• Simplest lipids: long hydrocarbon chains with a carboxylic acid head group.

• Hydrophobic chains with a hydrophilic head group, giving them amphipathic properties.

• The head group is generally ionized in solution, contributing to their reactivity and solubility.

• Amphiphilic nature allows for self-assembly into micelles or bilayers in aqueous environments.

• The acid group enables attachment to other molecules like amino acids and carbohydrates; acts like a "gluey end", facilitating the formation of more complex molecules.

• Palmitic acid: a large component of human fat.

• Fatty acids exist mostly in the form of esters, forming triglycerides and phospholipids.

• Chain length typically 18-20 carbons long, influencing their physical properties.

• Key labels: saturated and unsaturated.

  • Saturated: no double bonds, allowing close packing and solid consistency at room temperature.

  • Unsaturated: double bonds, introducing kinks in the chain that prevent close packing and result in liquid or soft consistency.

• Generally, saturated fatty acids are considered bad, and unsaturated (non-trans) are considered good for dietary health due to their effects on cholesterol levels.

• Saturated fats are typically found in butter, unsaturated in margarine.

• Solid fats vs liquid or soft fats are determined by the presence of double bonds influencing chain packing.

• Examples of saturated fatty acids: acetic acid, loric acid, stearic acid, commonly found in animal fats and some plant oils.

• Unsaturated fatty acids can be cis or trans; can have multiple double bonds.

• Examples of unsaturated fatty acids: oleic acid, arachidonic acid, abundant in olive oil and fish oil, respectively.

• Common names are typically used for acids in biology rather than chemical names for simplicity.

• Monounsaturated: one double bond, providing some flexibility and fluidity.

• Polyunsaturated: multiple double bonds, further enhancing fluidity and flexibility.

Fatty Acids as Acids

• Fatty acids are acidic (Bronsted acids), capable of donating protons.

• Exist in equilibrium, giving up hydrogen, influencing the pH of their environment.

• pKa typically around 4-5, indicating weak acidity.

• Body acidity is around 6-7, so fatty acids in the body are mostly ionized (minus form), making them chemically reactive.

• This contributes to their amphiphilic nature, enhancing their ability to interact with both polar and nonpolar environments.

• pKa of 4 is not super acidic; it's like vinegar (acetic acid).

• Not strong enough to destroy evidence like in "Breaking Bad", illustrating a relatable context.

• pKa of 4-5 is acidic enough to be ionized but not dangerously acidic, allowing them to participate in biochemical reactions without causing harm.

Glycerides and Phospholipids

• Most fatty acids exist in the form of esters, linking them to glycerol or other molecules.

• Glycerides are compound esters of glycerol and fatty acids, serving as energy storage molecules.

• Industrially important for isolating fatty acids and glycerol, facilitating the production of soaps, detergents, and other products.

• Monoglyceride: one ester group, used as emulsifiers in food processing.

• Diglyceride: two ester groups, involved in cell signaling.

• Triglyceride: three ester groups, the main component of body fat.

• Chain lengths in glycerides vary; can be saturated, unsaturated, polyunsaturated, affecting their physical properties and health implications.

• Glycerides are reservoirs of fat in the body, providing insulation and energy storage.

• Phospholipids are more complex; glycerol with two ester groups and a phosphate on the upper position, forming the structural basis of cell membranes.

• Various molecules can attach to the phosphate: ethanolamine, choline, serine, inositol, influencing membrane properties and cell signaling.

  • Ethanolamine and choline are most common, contributing to the diversity of phospholipids.

  • Ethanolamine is two carbons with a nitrogen, involved in neurotransmitter synthesis.

Sphingolipids

• Sphingosine: no ester group, officially linked, forming the backbone of sphingolipids.

• Ceramide, sphingomyelin (phosphate group added).

• Key difference: amide bond instead of ester bond, influencing their stability and function.

• Direct carbon bond up to the phosphate, distinguishing them from glycerophospholipids.

• Sphingolipids, involved in cell signaling and membrane structure.

Steroids

• Steroids are considered lipids with a cyclic skeleton, characterized by their fused ring structure.

  • Contain cyclohexanes and cyclopentanes, providing rigidity and shape.

• Stereochemistry is important; defines shape, influencing their interactions with biological molecules.

• Limited flexibility due to cyclic structure, leading to defined shapes.

• Shapes help interact with enzymes and receptors, enabling their hormonal and regulatory functions.

• Steroids as hormones: regulate physiological activities and homeostasis; act as chemical messengers.

• Cholesterol: important for cellular structure, maintaining membrane fluidity and permeability.

• Examples: Testosterone, hydrocortisone, cholesterol, showcasing their diverse roles.

• Testosterone: Men tend to have more than women, influencing sexual development and muscle mass.

• Hydrocortisone cream: used for eczema and to reduce inflammation and allergies, insect bites.

• Structure of steroids: 6-6-6-5 ring structure despite different functions, providing a common framework for their diverse biological activities.

Membrane Lipids

• Cell membranes are mainly made of lipids, forming a selectively permeable barrier.

• Long hydrocarbon tails, glycerol group attached to the phosphate, phosphate attached to various molecules like choline, creating amphiphilic structures.

• Typically, one chain has a double bond, creating a kink, enhancing membrane fluidity.

• C18 hydrocarbon (octadecane): a solid or wax at room temperature, illustrating the effect of chain length on physical properties.

• Body temperature is slightly above room temperature, maintaining membrane fluidity.

• Solid fats are undesirable in the body; oily or waxy fats are preferred, preventing arterial plaque formation.

• Double bonds inhibit solidification by preventing chains from co-crystallizing, ensuring proper membrane function.

• Chains can be unsaturated with mismatched lengths to prevent solidification, adding another layer of control over membrane fluidity.

• Ether phosphate linkages and ester-forming phosphate linkages, influencing the stability and reactivity of membrane lipids.

• Lipids are amphiphilic: hydrophilic heads, hydrophobic tails, allowing them to form bilayers in aqueous environments.

• In a water environment, phosphate groups (charged) interact with water, leading to self-assembly into bilayers.

• Two alkyl chains force the formation of a bilayer membrane instead of small cells, creating a stable and functional barrier.

Lipid Bilayer and Drug Delivery

• Hydrophobic chains assemble to avoid water, driven by the hydrophobic effect.

• This is the most thermodynamically stable arrangement in water, minimizing the interaction between nonpolar chains and water.

• Proteins and carbohydrates help hold the membrane together, providing structural support and functionality.

• Lipid bilayer is fluid and relatively impermeable, controlling the movement of substances in and out of the cell.

• Ions (positive or negative) have difficulty traversing the hydrophobic layer, requiring ion channels for transport.

• Nonpolar molecules can get through more easily but face issues getting into the water, limiting their bioavailability.

• Key problem: getting drugs through the membrane or into water, a major challenge in drug development.

• Cell membrane is a focus of drug studies, aiming to enhance drug delivery and efficacy.

• Protein molecules span the lipid bilayer, acting as ion channels, receptors, and transporters, mediating communication and transport across the membrane.

Membrane Fluidity and Components

• All components within the lipid bilayer are mobile, allowing for dynamic rearrangement.

• Lateral diffusion, flip-flop, rotation, and bending occur, contributing to the fluidity and flexibility of the membrane.

• Membrane fluidity is key, influencing various cellular processes like signaling and transport.

• Membranes can fuse and reproduce, essential for cell growth and division.

• Cell's plasma membrane: flexible and fluid, adapting to changing conditions.

• Cholesterol: influences membrane fluidity; more cholesterol decreases fluidity at high temperatures and increases it at low temperatures.

• Different cells have different membrane fluidity needs, depending on their function and environment.

• Cell membranes differ on the outside from the inside, creating asymmetry in lipid and protein distribution.

• Glycolipids and glycoproteins: carbohydrates attached to lipids or proteins, involved in cell-cell recognition and signaling.

• Outside of the cell has phosphorus groups and proteins, facilitating interactions with the external environment.