Lipids: Structure, Types, and Function

• Lipids are hydrophobic, amphipathic molecules with hydrophobic tails and hydrophilic heads.

Major Types of Lipids

• Fatty acids can be saturated, meaning they have no double bonds, or unsaturated, meaning they have one or more double bonds.
• Triglycerides are used for energy storage and are called oils in plants and fats in animals.
• Phospholipids are key components of membrane structure, including glycerophospholipids and sphingolipids.
• Steroids, such as cholesterol, affect membrane fluidity and are used for hormone synthesis.
• Glycolipids are involved in cell signaling and recognition.

Fatty Acids

• Saturated fatty acids pack tightly and have higher melting points.
• Unsaturated fatty acids have kinks due to cis double bonds, resulting in lower melting points.
• Essential fatty acids include Omega-3 (α-linolenic acid) and Omega-6 (linoleic acid).

Membrane Structure and Fluidity

• The fluid mosaic model describes the dynamic movement of lipids and proteins laterally within the membrane.
• Membranes are typically 60-100 Å thick, with a hydrophobic core of about 30 Å.
• Cholesterol increases membrane fluidity at low temperatures and decreases it at high temperatures.

Membrane Asymmetry

• The outer leaflet of the cell membrane mainly contains Phosphatidylcholine (PC) and Sphingomyelin (SM).
• The inner leaflet mainly contains Phosphatidylethanolamine (PE), Phosphatidylserine (PS), and Phosphatidylinositol (PI).

Lipid Functions Beyond Membranes

• White adipose tissue (WAT) stores energy.
• Brown adipose tissue (BAT) produces heat (thermogenesis) using uncoupling protein 1 (UCP1).

Other Roles of Lipids

• Coenzyme Q10 (Ubiquinone) acts as an electron carrier in the mitochondrial electron transport chain.
• Lipid pigments like carotenoids (e.g., canthaxanthin) provide color.
• Eicosanoids (from arachidonic acid) and jasmonate (in plants) function as lipid signaling molecules.

Lipid Metabolism

• Acetyl-CoA serves as a central metabolic intermediate.
• Fatty acid synthesis occurs in the cytosol, converting Acetyl-CoA to Malonyl-CoA and then to fatty acids.
• Cholesterol synthesis also occurs in the cytosol, converting Acetyl-CoA to HMG-CoA, then to Mevalonate, and finally to Cholesterol.
• Ketone bodies are synthesized in the liver mitochondria, converting Acetyl-CoA to Acetoacetate, β-Hydroxybutyrate, and Acetone.

Fatty Acid Oxidation (β-Oxidation)

• Occurs in mitochondria.
• Generates Acetyl-CoA, NADH, and FADH2, which lead to ATP production via the TCA cycle and ETC.

Ketone Bodies

• Produced during fasting or when carbohydrate intake is low.
• The brain uses ketone bodies as fuel when glucose levels are low.

Ion Channels and Membrane Potential

• Ligand-gated ion channels open upon neurotransmitter binding.
• Examples include the Cys-loop family (AchR, GABA, Glycine, 5-HT₃) and ionotropic Glutamate Receptors (iGluRs) like AMPA, NMDA, and Kainate, which have a tetrameric structure.
• The AchR pore diameter is approximately 6.5 Å, allowing Na⁺ and K⁺ to flow through.

Voltage-Gated Ion Channels

• Open in response to changes in membrane potential.
• Examples: Na⁺, K⁺, and Ca²⁺ channels
• Selectivity filters determine ion specificity; for example, the K⁺ channel is 4 Å, and the Na⁺ channel favors Na⁺ based on size.
• The ball-and-chain model describes the mechanism of channel inactivation.
• The resting membrane potential is about -70 mV.
• Action potentials propagate at a speed of around 100 m/s.

Patch-Clamp Technique

• Measures ion channel activity in cells, either in whole-cell or single-channel configurations.

Membrane Transporters

• Passive transport does not require energy and is driven by concentration gradients.
• Active transport requires ATP or ion gradients.
• Primary active transport uses ATP hydrolysis, like the Na+/K+ ATPase.
• Secondary active transport uses ion gradients, like the Na+/Glucose Symporter.

Key Transporters

• The Na+/K+ ATPase (P-Type ATPase) pumps 3 Na⁺ out and 2 K⁺ in while hydrolyzing 1 ATP. This maintains the electrochemical gradient, resting potential, cell volume, and supports secondary transport. It follows the E1-E2 cycle of conformational states during transport and consumes 70-80% of ATP in neurons.
• Calcium ATPase (SERCA) pumps Ca²⁺ into the sarcoplasmic reticulum after muscle contraction.
• The Na+/Ca²⁺ Exchanger (NCX) exchanges 1 Ca²⁺ out for 3 Na⁺ in, and the direction is reversible based on the ion gradients.
• Aquaporins are water channels that facilitate passive osmosis and can transport approximately 3 × 10⁹ water molecules per second per subunit.
• Solute Carrier Transporters (SLCs) include GABA Transporters (GAT), which are Na⁺/Cl⁻ dependent, and Excitatory Amino Acid Transporters (EAATs), which remove glutamate from the synapse to prevent excitotoxicity.