3.3 Lipids

Lipids are a diverse group of biomolecules united by one key trait: they don't dissolve well in water. This hydrophobic character gives them unique biological roles, from storing energy in fats to forming the membranes that surround every cell. They also include steroids like cholesterol, which fine-tune membrane properties and serve as precursors for hormones.

Lipid Categories and Characteristics

Categories of lipids

There are four major categories of lipids, each with a distinct structure and biological role.

• Fats (triglycerides)
  • Composed of a glycerol molecule bonded to three fatty acid chains via ester bonds
  • Serve as the primary long-term energy storage molecules, stored mainly in adipose tissue
  • Nonpolar and hydrophobic because their long hydrocarbon chains dominate the structure
• Phospholipids
  • Built from a glycerol backbone, two fatty acid chains, and a phosphate group bonded to a polar molecule (such as choline, serine, or ethanolamine)
  • Amphipathic: they have a hydrophilic (water-loving) head and hydrophobic (water-fearing) tails
  • Form the structural basis of all biological membranes, including cell membranes and organelle membranes
• Steroids
  • Defined by four fused carbon rings (three six-carbon cyclohexane rings and one five-carbon cyclopentane ring), with various functional groups attached
  • Include cholesterol (a membrane component), steroid hormones (testosterone, estrogen, cortisol), and bile acids (which aid lipid digestion)
  • Involved in cell signaling, reproduction, and digestion
• Waxes
  • Composed of long-chain fatty acids esterified to long-chain alcohols
  • Provide protective, water-repellent coatings, such as the cuticle on plant leaves and the exoskeletons of insects
  • Also serve as energy storage in some organisms, including certain plankton

Fats as energy storage

Fats store more energy per gram than any other macromolecule. This makes them the body's most efficient fuel reserve.

• High energy density: Fats yield about $9 \text{ kcal/g}$, compared to roughly $4 \text{ kcal/g}$ for carbohydrates and proteins. This is because fats contain a higher proportion of energy-rich C-H bonds.
• Compact, anhydrous storage: Unlike glycogen (which binds water), fat is stored in a nearly water-free form, so you can pack a lot of energy into a small space.
• Stored in adipocytes: These specialized cells contain large lipid droplets surrounded by a phospholipid monolayer. The droplets expand or shrink depending on whether the body is storing or burning energy.
• Insulation and cushioning: A subcutaneous fat layer beneath the skin helps regulate body temperature by reducing heat loss. Visceral fat surrounds and cushions internal organs against mechanical damage.

Saturated vs unsaturated fatty acids

The distinction between saturated and unsaturated fatty acids comes down to the bonds between carbon atoms in the hydrocarbon chain, and it has a big effect on physical properties.

• Saturated fatty acids
  • Contain only single bonds between carbons
  • Their straight chains pack tightly together, maximizing van der Waals interactions between neighboring molecules
  • Result: higher melting points, so they tend to be solid at room temperature (think butter, animal fat)
• Unsaturated fatty acids
  • Contain one or more C=C double bonds (monounsaturated = one; polyunsaturated = more than one)
  • Each double bond introduces a kink in the chain, preventing tight packing
  • Result: lower melting points, so they tend to be liquid at room temperature (think olive oil, fish oil)
• Cis vs. trans configurations
  • Cis: the hydrogens on either side of the double bond are on the same side. This is the naturally occurring form and creates the characteristic kink.
  • Trans: the hydrogens are on opposite sides. Trans fats typically result from industrial partial hydrogenation and produce straighter chains that behave more like saturated fats. Trans fats are associated with increased cardiovascular disease risk.

Phospholipids in cell membranes

Phospholipids are the architectural foundation of biological membranes. Their amphipathic nature drives membrane assembly and determines many membrane properties.

• Amphipathic structure
  • The hydrophilic head consists of a phosphate group linked to a polar molecule (choline, serine, or ethanolamine)
  • The hydrophobic tail region consists of two fatty acid chains, often one saturated and one unsaturated
• Spontaneous bilayer formation: When placed in water, phospholipids self-assemble into a bilayer. The hydrophilic heads face outward toward the aqueous environment on both sides, while the hydrophobic tails face inward, creating a nonpolar interior.
• Selective permeability: This bilayer acts as a barrier that controls what enters and exits the cell. Small, nonpolar molecules (like $O_2$ and $CO_2$) cross easily, while large or charged molecules generally cannot pass without help from transport proteins.
• Membrane fluidity depends on fatty acid composition:
  • Unsaturated fatty acid tails increase fluidity because their kinks prevent tight packing
  • Saturated fatty acid tails decrease fluidity by allowing tighter packing
  • Proper fluidity is essential for membrane protein function and processes like endocytosis and exocytosis

Structure and functions of steroids

Steroids look completely different from other lipids. Instead of long fatty acid chains, they're built around a compact ring structure.

• Four fused carbon rings form the steroid nucleus: three cyclohexane rings and one cyclopentane ring. Different functional groups (hydroxyl, ketone, alkene) attached to this skeleton determine which specific steroid it is.
• Cholesterol
  • The most common steroid in animal cells
  • Serves as the precursor for synthesis of all other steroid hormones
  • An essential structural component of animal cell membranes
• Steroid hormones
  • Derived from cholesterol through enzymatic modifications
  • Because they're lipid-soluble, they can cross the plasma membrane and bind to intracellular receptors (unlike water-soluble hormones, which bind receptors on the cell surface)
  • Regulate development, reproduction, metabolism, and immune function (examples: testosterone, estrogen, cortisol)
• Bile acids
  • Synthesized from cholesterol in the liver
  • Act as emulsifiers in the small intestine, breaking large fat globules into smaller droplets so lipases can access them more efficiently
  • Also help excrete excess cholesterol and waste products like bilirubin
• Vitamin D
  • A steroid-derived molecule synthesized from cholesterol in the skin when exposed to UV light
  • Regulates calcium and phosphate levels in the blood, promoting bone mineralization

Cholesterol's impact on membranes

Cholesterol plays a dual role in membrane fluidity, acting as a buffer that keeps fluidity within a functional range.

• At high temperatures, cholesterol intercalates between phospholipids and restricts their movement, reducing fluidity and preventing the membrane from becoming too loose or leaky.
• At low temperatures, cholesterol disrupts the tight packing of phospholipid tails, increasing fluidity and preventing the membrane from becoming rigid or solidifying.

This buffering effect is sometimes called cholesterol's "fluidity buffer" role.

• Membrane stability: Cholesterol interacts with saturated fatty acid tails to reduce permeability to small water-soluble molecules. It also provides mechanical strength, particularly in cholesterol-rich regions called lipid rafts.
• Cholesterol-to-phospholipid ratio varies across membranes to match their function:
  • Higher ratios (like in the plasma membrane) produce decreased fluidity and increased stability
  • Lower ratios (like in the endoplasmic reticulum or Golgi membranes) allow greater fluidity
  • Specialized membranes such as myelin sheaths and synaptic vesicles have ratios tuned to their specific roles

Lipid Metabolism

Lipid metabolism covers how the body builds, breaks down, and transports lipids.

• Hydrolysis of lipids: Enzymes called lipases break ester bonds in triglycerides by adding water, releasing glycerol and free fatty acids. This is the first step in using stored fat for energy.
• Beta-oxidation: Once freed, fatty acids enter the mitochondria and are broken down two carbons at a time into acetyl-CoA. Each round of beta-oxidation also produces $NADH$ and $FADH_2$, which feed into the electron transport chain. The acetyl-CoA enters the citric acid cycle. This is why fats yield so much ATP.
• Lipogenesis: When the body has excess energy (especially from carbohydrates), it synthesizes fatty acids from acetyl-CoA. This occurs mainly in the liver and adipose tissue, with fatty acid synthase as the key enzyme. Hormones like insulin promote lipogenesis.
• Lipid transport: Because lipids are hydrophobic, they can't travel freely in the blood. Instead, they're packaged into lipoproteins, which have a hydrophilic exterior and a lipid-rich core. Two important types:
  • LDL (low-density lipoprotein) delivers cholesterol to tissues; excess LDL is associated with plaque buildup in arteries
  • HDL (high-density lipoprotein) transports cholesterol back to the liver for disposal; often called "good cholesterol"