RB

Biochemistry of Lipids, Membranes, and Carbohydrates (Chapters 1-8)

Soap, hydrogenation, and soap formation

  • Hydrogenation of fatty acids: breaking the double bond to convert unsaturated fats into saturated fats, giving the fat the same physical properties as saturated fat (solids at room temperature). Derived from oils; the process is called hydrogenation.
  • Base-catalyzed ester hydrolysis (saponification): reacting fats with a base to form a salt (soap) and glycerol. This salt is amphipathic and tends to form micelles in water to emulsify oils/dirt.
  • Micelle formation and cleaning mechanism: the amphipathic salt aggregates such that the hydrophobic tails sequester oil/dirt inside, while hydrophilic heads face water, enabling dirt/oil to be washed away in water.

Membranes, lipids, and self-assembly

  • Lipids can form structures due to amphipathicity: micelles, bilayers, and liposomes.
  • Micelle vs bilayer concept:
    • Micelles: typically form when single-tailed amphipaths aggregate with hydrophilic heads outward, hydrophobic tails inward.
    • Bilayers (lipid bilayers): two layers of lipids arranged tail-to-tail, forming a hydrophobic interior and hydrophilic exterior surfaces; this is the basic structure of cell membranes.
  • Liposomes: a vesicle with a phospholipid bilayer where the hydrophilic heads face the aqueous interior and exterior, and the hydrophobic tails are in the middle; water cannot freely cross the membrane
    • Conceptual tool to illustrate membrane properties; not a literal cell but demonstrates how water-soluble and lipophilic components partition.
  • Proteins and glycolipids: membranes can have proteins attached; glycolipids (sugars attached to lipids) are present and contribute to cell surface identity (cell recognition).
  • Placing sugars on proteins or lipids in membranes provides self-recognition markers (cell-type/tissue identity). This is why matching sugars matters in contexts like blood typing and tissue compatibility.

Phospholipids, membrane structure, and fluidity

  • Phospholipids: amphipathic molecules with a hydrophilic head and hydrophobic tails; form lipid bilayers.
  • Bilayer arrangement: outer surface faces water on both sides; inner membrane interior is hydrophobic, forming a barrier to most polar molecules; this supports selective transport.
  • Cholesterol's role: inserts between phospholipid tails and provides rigidity to the membrane, helping prevent excessive fluidity and collapse; contributes to membrane mechanical stability.
  • Cholesterol as a sterol: cholesterol has a four-ring steroid structure; steroids are built on the steroid nucleus; its presence modulates membrane properties and can be precursors to steroid hormones.
  • Sphingolipids and backbone diversity: some membranes use sphingosine backbones; these lipids intersperse within membranes and contribute to rigidity.
  • Membrane rigidity vs fluidity: unsaturated fatty acids with one or more double bonds increase spacing between tails and enhance fluidity; saturated tails (no double bonds) pack tightly and reduce fluidity; a balance is needed for proper cellular function.
  • Eggs and choline/phosphatidylcholine: in eggs, phosphatidylcholine helps emulsify fats and participates in lipid interactions akin to membrane components.
  • Lipids in health and disease: membrane composition influences permeability and protein function; cholesterol and glycolipids participate in cell signaling and recognition.

Lipids, cholesterol, and disease mechanisms

  • Glycolipids and brain health: glycolipids (sugars attached to lipids) are abundant in the brain and nervous system and contribute to cell recognition and signaling; abnormalities can be involved in diseases.
  • Tay-Sachs and glycolipids: Tay-Sachs disease involves glycolipid accumulation (GM2 ganglioside) due to a deficiency in a lysosomal enzyme, leading to neurodegeneration in infants; related to reduced breakdown of glycolipids.
  • Peroxisomal disorders (e.g., Heme and Pex disorders): related to metabolism of lipids and glycolipids; disruptions can lead to neurodevelopmental issues.
  • Prostaglandins, leukotrienes, and thromboxanes (eicosanoids): derived from arachidonic acid (a fatty acid precursor).
  • Arachidonic acid pathway: release of arachidonic acid and metabolism by cyclooxygenase (COX) and lipoxygenase pathways to produce prostaglandins, thromboxanes, and leukotrienes; these signaling lipids regulate inflammation, pain, and vascular/airway tone.
  • COX enzymes and drug interactions:
    • Aspirin inhibits cyclooxygenase (COX), reducing production of prostaglandins and thromboxanes; this contributes to pain relief and reduced platelet aggregation (blood thinning).
    • Tylenol (acetaminophen) is described as particularly dangerous at high doses due to liver toxicity, and caution is advised when combining with other analgesics.
  • Prostaglandins: diverse roles including pain signaling, smooth muscle relaxation/dilation, and involvement in reproductive processes (e.g., cervical ripening during labor; prostaglandins can promote cervical dilation; oxytocin/pitocin can promote uterine contractions).
  • Thromboxanes: promote platelet aggregation and clot formation; inhibition helps reduce clotting risk.
  • Leukotrienes: mainly involved in inflammatory responses and bronchoconstriction; steroids can mitigate inflammatory responses and airway constriction.

Complex lipids and lipoproteins (transport through blood)

  • Complex lipids include lipoproteins: lipid-protein particles that transport lipids through the bloodstream; structure resembles micelles with a protein-rich exterior and lipid-rich interior that is not water-soluble.
  • Four main lipoprotein classes:
    • Chylomicrons: transport dietary triglycerides from the intestine to adipocytes and tissues after a fatty meal.
    • Very Low Density Lipoprotein (VLDL): transports triglycerides synthesized by the liver to peripheral tissues.
    • Low Density Lipoprotein (LDL): carries cholesterol (primarily cholesterol esters) to membranes and tissues; often used as a biomarker for blood cholesterol levels because cholesterol is carried within lipoproteins rather than freely dissolved.
    • High Density Lipoprotein (HDL): scavenges cholesterol from tissues and carries it back to the liver for disposal (the so-called “good” cholesterol, though lipids are not inherently good or bad—distribution and context matter).
  • Lipoprotein composition and relative abundance:
    • Lipoproteins that carry high triglyceride content (e.g., chylomicrons, VLDL) have lipid cores rich in triglycerides.
    • LDL cores contain cholesterol esters; HDL is protein-rich with less core lipid relative to protein content.
    • The outer shell of lipoproteins contains phospholipids and cholesterol; surface proteins mediate receptor binding and cellular uptake.
  • Cellular uptake and receptors:
    • LDL particles must bind to LDL receptors on the cell surface to be internalized; cells without receptors do not internalize LDL.
    • HDL functions in reverse cholesterol transport by picking up cholesterol from tissues and delivering it to the liver.
  • Clinical context for measurements:
    • In practice, you measure lipoprotein levels to estimate cholesterol burden, since cholesterol itself is carried primarily by lipoproteins when in blood.
    • High circulating LDL relative to HDL can indicate higher risk for cardiovascular disease; HDL is protective by facilitating cholesterol clearance.
  • General lipoprotein structure (simplified): Outer shell of phospholipids and cholesterol with embedded proteins; a hydrophobic core containing triglycerides and cholesterol esters; interior is water-inaccessible, protecting lipids from the aqueous environment.
  • Practical note on exam focus: know the four main lipoproteins and their primary function in lipid transport; know that LDL binds to cell receptors and HDL participates in reverse cholesterol transport.

Carbohydrates: classes, structure, digestion, and identity

  • General properties: carbohydrates are highly hydrophilic due to many hydroxyl groups and are water-soluble; storage and energy roles are central.
  • Classification framework:
    • Aldehyde vs ketone functionality (aldehydes vs ketones) and the carbon count influence classification (e.g., aldoses vs ketoses).
    • Polyhydroxylated carbohydrates are typical (many OH groups).
    • Plant origin: many carbohydrates are synthesized by plants; storage forms in plants include starch.
  • Simple vs complex carbohydrates:
    • Monosaccharides (one sugar): glucose, fructose. Examples are used to identify which are monosaccharides on exams.
    • Disaccharides (two monosaccharides linked): sucrose, lactose, maltose. Each has a specific glycosidic bond and enzyme required for hydrolysis:
    • Sucrose requires sucrase to break its glycosidic bond.
    • Lactose requires lactase to break its glycosidic bond.
    • Maltose requires a specific maltase to break its bond (not always listed, but maltase is the enzyme for maltose).
    • Oligosaccharides: 3–10 sugars linked together; commonly found on glycoproteins and glycolipids on cell surfaces; important for cell recognition and self/non-self identification.
    • Polysaccharides: many sugars (>10, often hundreds or thousands) and can be branched or unbranched
    • Examples: starch, glycogen (energy storage), cellulose (structural in plants; dietary fiber in humans).
  • Glycosidic bonds and enzyme specificity:
    • Glycosidic bonds join monosaccharides; breaking them requires specific enzymes (e.g., sucrase breaks sucrose; lactase breaks lactose).
    • In biology, disaccharides are typically not used directly for energy; they must be hydrolyzed to monosaccharides first (
      e.g., glucose or galactose) before entering glycolysis.
  • Glycoproteins and glycolipids: carbohydrates on proteins and lipids form oligosaccharides that serve as cellular identity markers (e.g., blood group antigens) and mediate cell-cell recognition.
  • Specific sugar examples and roles:
    • Monosaccharides: glucose, fructose.
    • Disaccharides: sucrose (glucose + fructose), lactose (galactose + glucose), maltose (glucose + glucose).
    • Polysaccharides: starch (amylose/amylopectin) for energy storage in plants; glycogen for energy storage in animals; cellulose as plant structural carbohydrate (indigestible fiber in humans).
    • Chitin: structural polysaccharide in exoskeletons (insects, crustaceans) and fungi; another example of a polysaccharide not digestible by humans.
  • Plant- and fiber-related notes:
    • Cellulose fiber contributes to digestive bulk in humans and cannot be broken down by human enzymes.
  • Chirality and stereochemistry in carbohydrates:
    • Carbons with four different substituents are chiral; molecules can have non-superimposable mirror images (enantiomers).
    • Enantiomers are mirror images; diastereomers are stereoisomers that are not mirror images of each other.
    • Stereoisomerism is a family of isomers that differ in spatial arrangement, not in molecular formula.
  • Anomeric configuration and glycosidic linkages (glycosidic bonds):
    • Glycosidic bonds connect monosaccharides to form disaccharides and longer chains; their orientation (alpha vs beta) affects digestibility and enzyme recognition.
  • Practical exam notes:
    • Focus on identifying whether a given carbohydrate is monosaccharide, disaccharide, or polysaccharide.
    • Know key examples: monosaccharides (glucose, fructose); disaccharides (sucrose, lactose, maltose); polysaccharides (starch, glycogen, cellulose); oligosaccharides (3–10 sugars).
  • Blood group and cell-surface sugars:
    • The cell-surface oligosaccharides/glycoproteins/glycolipids contribute to tissue typing and blood group antigens; proper matching reduces immune recognition and rejection risk.

Quick reference: key terms and concepts (cross-topic)

  • Micelle: single-layer aggregate of amphipathic molecules in water, with hydrophobic cores.
  • Liposome: vesicle with a phospholipid bilayer; hydrophilic heads face water on both sides; interior aqueous compartment.
  • Lipoprotein: lipid-protein particle that transports lipids in blood; four classes—chylomicrons, VLDL, LDL, HDL.
  • Chylomicron: dietary triglyceride transport from intestine to tissues.
  • VLDL: transports endogenously synthesized triglycerides from liver to tissues.
  • LDL: carries cholesterol to tissues; receptor-mediated uptake; high levels associated with atherogenesis.
  • HDL: scavenges cholesterol from tissues to liver for disposal; considered protective.
  • Arachidonic acid: essential fatty acid precursor to eicosanoids (prostaglandins, thromboxanes, leukotrienes).
  • Prostaglandins: regulate pain, vasodilation/constriction, smooth muscle tone; involved in labor and cervical ripening.
  • Thromboxanes: promote platelet aggregation and clotting; target of COX inhibitors reduces clotting.
  • Leukotrienes: drive inflammation and bronchoconstriction; steroids can mitigate.
  • Cyclooxygenase (COX): enzyme that converts arachidonic acid to prostaglandins and thromboxanes; inhibited by aspirin.
  • Glycolipids and glycoproteins: sugars on lipids/proteins for cell recognition; important in immune compatibility and tissue typing.
  • Tay-Sachs disease: accumulation of glycolipids (GM2 ganglioside) due to enzyme deficiency; neurodegeneration in infants; carrier screening relevant in high-risk populations.
  • Glycosidic bond: linkage between sugars; requires specific enzymes for hydrolysis (e.g., sucrase for sucrose, lactase for lactose).
  • Monosaccharide vs disaccharide vs oligosaccharide vs polysaccharide: one sugar; two sugars; 3–10 sugars; many sugars, respectively.
  • Chiral center, enantiomer, diastereomer, stereoisomer: concepts describing three-dimensional orientation and mirror-image relationships in molecules.

Exam-oriented notes on carbohydrate topics (recap)

  • Know examples: monosaccharides (glucose, fructose); disaccharides (sucrose, lactose, maltose); polysaccharides (starch, glycogen, cellulose); oligosaccharides (3–10 sugars).
  • Understand glycosidic bonds and enzyme specificity (sucrase breaks sucrose; lactase breaks lactose).
  • Distinguish between digestible vs nondigestible polysaccharides (cellulose as fiber).
  • Recognize the role of oligosaccharides in cell surface recognition and blood typing.
  • Grasp basic stereochemistry concepts as they apply to sugars (enantiomers and diastereomers).

End of notes for this lecture

  • The upcoming class will review carbohydrates further and integrate with proteins and lipids for the exam, which will cover chapters 2 and 3, with carbohydrates as a primary focus. The planned in-class test on Monday will be around 30–35 multiple-choice questions in a 50-minute window, designed to resemble a shorter quiz in difficulty but comprehensive in content. Expect questions about lipid structure, lipoproteins, eicosanoids, and carbohydrate classification and bonds.