Lipids

Lipids are a diverse group of organic molecules that are primarily composed of carbon (C), hydrogen (H), and oxygen (O) atoms, with a much lower proportion of oxygen compared to carbohydrates. They are hydrophobic or amphipathic, meaning they do not dissolve well in water but can interact with both water and non-polar substances. Lipids play crucial roles in energy storage, cell membrane structure, and signaling.

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Lipids: Membranes and Energy

Main functions of lipids in biological systems include:

• biological membranes
• energy storage

Overview

Lipids are largely hydrophobic (non-polar) molecules; many are amphipathic (having both hydrophobic tails and hydrophilic heads). The hydrophobic effect drives their self-assembly in water, enabling membranes, vesicles, and lipid–protein complexes. Compared to Carbohydrates, lipids are more reduced (higher energy density) and are therefore the dominant long-term energy store in animals.

Building Blocks: Fatty Acids and Glycerol

• Fatty acids (FAs) are hydrocarbon chains with a terminal carboxyl group (–COOH).
• Chain length (short/medium/long) and degree of saturation (saturated vs. mono-/polyunsaturated) strongly influence melting temperature and membrane fluidity.
• Double-bond geometry: cis-kinks disrupt packing and increase fluidity; trans behaves more like saturated FAs.
• Triacylglycerols (TAGs) form by esterifying three fatty acids to glycerol (via ester linkages).

Example

Butter (rich in saturated FAs) is solid at room temperature, while olive oil (rich in cis-unsaturated FAs like oleic acid) is liquid due to poorer packing and lower melting point.

Major Classes of Lipids

• Triacylglycerols (TAGs): primary energy storage; stored in adipocytes; mobilized via lipases; yield ~9 kcal/g.
• Phospholipids (glycerophospholipids, sphingomyelin): amphipathic; major membrane components; headgroups include choline, ethanolamine, serine, inositol.
• Sterols (e.g., cholesterol): planar, rigid ring system; modulates membrane fluidity and permeability; precursor for steroid hormones and bile acids.
• Glycolipids: lipids with carbohydrate headgroups (often sphingolipids) important for cell–cell recognition and signaling at the outer leaflet.
• Eicosanoids (from arachidonic acid): local signaling molecules (prostaglandins, thromboxanes, leukotrienes) affecting inflammation, vascular tone, and platelet function.
• Fat-soluble vitamins: A, D, E, K are isoprenoid-derived lipids with roles in vision, calcium homeostasis, antioxidant protection, and coagulation.

Amphipathic Lipids and Self-Assembly

In aqueous environments lipids spontaneously organize to minimize free energy:

• Micelles: cone-shaped amphiphiles (single-tail detergents) form spherical structures that sequester hydrophobic tails inward.
• Bilayers: cylindrical amphiphiles (phospholipids) form planar sheets that can close into vesicles.
• Liposomes/vesicles: closed bilayers enclosing an aqueous lumen; basis for trafficking and drug delivery.

FYI

The hydrophobic effect is largely entropy-driven: water becomes less ordered when nonpolar surfaces cluster. Lipids do not “attract” each other strongly; they reduce the ordering penalty of surrounding water.

Biological Membranes

• Fluid mosaic model: a 2D fluid bilayer of lipids with embedded proteins; components diffuse laterally, while transverse flip-flop is slow and often enzyme-mediated (flippases, floppases, scramblases).
• Asymmetry: inner vs outer leaflet composition differs (e.g., PS, PE enriched cytosolic side; PC, sphingomyelin outer side); glycolipids face the extracellular space.
• Cholesterol buffers fluidity: restrains movement (reduces permeability) at high T; prevents tight packing and preserves fluidity at low T.
• Lipid rafts: ordered microdomains enriched in cholesterol and sphingolipids, proposed to organize signaling complexes.
• Permeability barrier: bilayers are selectively permeable—small nonpolar molecules pass readily, ions and polar solutes require transport proteins.

Factors Affecting Membrane Fluidity

• Temperature: higher T increases fluidity; organisms adjust lipid saturation and chain length with temperature.
• Saturation and chain length: more unsaturation and shorter chains increase fluidity; more saturation and longer chains decrease fluidity.
• Sterols (cholesterol): bidirectional regulation of order and permeability depending on temperature and lipid context.

Energy Storage and Metabolism

• TAGs pack densely and anhydrously, giving high energy density compared with glycogen (which is hydrated and branched for rapid access).
• Mobilization: hormone-sensitive lipases release fatty acids, which undergo β-oxidation to acetyl-CoA for ATP production; liver can convert excess acetyl-CoA to ketone bodies.
• Essential fatty acids (linoleic, α-linolenic) are precursors for longer polyunsaturated fatty acids (e.g., arachidonic acid, DHA) with structural and signaling roles.

Signaling and Recognition

• Steroid hormones (e.g., cortisol, estradiol, testosterone) derive from cholesterol and act via nuclear receptors to regulate gene expression.
• Eicosanoids act locally and rapidly; NSAIDs (e.g., aspirin) target cyclooxygenases involved in prostaglandin synthesis.
• Glycolipids contribute to cell identity and immune recognition (e.g., blood group antigens).

Intermolecular Forces and Water

• Hydrophobic effect drives aggregation in water; van der Waals interactions stabilize packed tails.
• Hydrogen bonding occurs among headgroups and with water; electrostatic interactions among charged headgroups influence packing and protein binding.

Summary

• Lipids are hydrophobic/amphipathic molecules central to membranes, energy storage, and signaling.
• Structure (chain length, saturation, headgroup) determines physical properties and biological roles.
• Amphipathic lipids self-assemble into micelles, bilayers, and vesicles; membranes follow the fluid mosaic model with regulated fluidity and asymmetry.
• Triacylglycerols store energy efficiently; sterols and phospholipids sculpt membrane behavior; specialized lipids enable signaling and recognition.