Lipid

• 1. Introduction

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  Lipids are the reason a migratory bird can fly for days without eating, and the reason you cannot mix oil and water. They are a broad group of organic compounds that includes fats, waxes, sterols, and the fat-soluble vitamins A, D, E and K. The word itself stems from the Greek lipos, meaning fat. Yet that single English word hides a startling range. A lipid can store energy, send a signal between cells, or build the wall of a cell membrane. The same family supplies cosmetics, food products, and nanotechnology. Lipids are defined as hydrophobic or amphiphilic small molecules. That amphiphilic nature lets some of them assemble into vesicles, liposomes, and membranes the moment they meet water. How did chemists come to gather oils, brain matter, cholesterol, and antibiotics under one heading? Why can the human body make many lipids but not all of them? And how does a molecule that refuses to dissolve in water end up forming the boundary of every living cell?

• 2. Naming The Fat

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  In 1815, Henri Braconnot sorted these greasy substances into just two bins: suifs, the solid tallows, and huiles, the fluid oils. Eight years later, in 1823, Michel Eugene Chevreul built a finer scheme that added greases, waxes, resins, balsams, and volatile or essential oils. The categories were multiplying faster than anyone could agree on a name for the whole group.

  In 1827, William Prout placed fat alongside protein and carbohydrate as one of the important nutrients for humans and animals. He described fat as the oily alimentary matter, protein as the albuminous, and carbohydrate as the saccharine. That nutritional trinity gave fats a clear role in the diet.

  Theodore Gobley, in 1847, found something the old categories could not hold. Working with mammalian brain and hen egg, he discovered phospholipids and named them lecithins. Thudichum later pulled more surprises from the human brain: a phospholipid called cephalin, a glycolipid called cerebroside, and a sphingolipid called sphingomyelin. Fats were turning out to be far stranger than tallow and oil.

  The vocabulary stayed in flux for decades. The terms lipoid, lipin, lipide, and lipid drifted in meaning from author to author. In 1912, Rosenbloom and Gies proposed replacing lipoid with lipin. In 1920, Bloor offered yet another classification, splitting lipoids into simple, compound, and derived. The word lipide finally arrived in 1923, coined by the French pharmacologist Gabriel Bertrand. He folded both the traditional glycerides and the complex lipoids into one concept. The international commission of the Societe de Chimie Biologique approved the word unanimously during its plenary session on the 3rd of July 1923.

• 3. Building From Two Blocks

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  Every biological lipid traces back to one of two building-blocks: ketoacyl groups or isoprene groups. This single distinction lets chemists divide the entire family into eight categories. Six come from the condensation of ketoacyl subunits: fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, and polyketides. Two come from isoprene subunits: sterol lipids and prenol lipids. The Lipid MAPS consortium uses exactly these eight headings.

  Fatty acyls are the most fundamental of the categories, built by chain-elongation of an acetyl-CoA primer in a process called fatty acid synthesis. Each is a hydrocarbon chain ending in a carboxylic acid group. That gives one polar, water-loving end and one nonpolar end that water rejects. The carbon chain usually runs between four and 24 carbons. A double bond in the cis configuration bends the chain, and more double bonds bend it further. The three double bonds in 18-carbon linolenic acid keep plant thylakoid membranes highly fluid even in low temperatures.

  Glycerolipids are built on glycerol, the best known being the triglycerides, the fatty acid triesters of glycerol. In these, all three hydroxyl groups of glycerol are esterified, typically by different fatty acids. Glycerophospholipids carry the same glycerol backbone but add a phosphate-linked head group. Subclasses include phosphatidylcholine, also called lecithin, phosphatidylethanolamine, and phosphatidylserine.

  Sphingolipids start not from glycerol but from a sphingoid base, synthesized de novo from the amino acid serine and a long-chain fatty acyl CoA. The major sphingoid base of mammals is sphingosine. Insects favor ceramide phosphoethanolamines, while fungi build phytoceramide phosphoinositols. Saccharolipids swap a sugar in for the glycerol backbone entirely; the most familiar are the Lipid A precursors in the lipopolysaccharides of Gram-negative bacteria.

  Polyketides round out the ketoacyl side and stand apart from the rest. They are assembled by polymerizing acetyl and propionyl subunits, often into cyclic molecules. Many commonly used antimicrobial, antiparasitic, and anticancer agents are polyketides or their derivatives, including erythromycins, tetracyclines, avermectins, and the antitumor epothilones.

• 4. From Isoprene

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  Prenol lipids begin with two five-carbon units: isopentenyl diphosphate and dimethylallyl diphosphate, produced mainly through the mevalonic acid pathway. Adding C5 units one after another builds the simple isoprenoids. Structures past 40 carbons are called polyterpenes. Carotenoids, important simple isoprenoids, work as antioxidants and as precursors of vitamin A. Vitamin E, vitamin K, and the ubiquinones belong to a related class with an isoprenoid tail on a quinonoid core. In bacteria the terminal isoprenoid unit stays unsaturated, forming bactoprenols, while in animal dolichols that terminal unit is reduced.

  Sterols are the other isoprene-derived branch and a key component of membrane lipids. Cholesterol is the predominant example. The plant equivalents are phytosterols such as beta-sitosterol, stigmasterol, and brassicasterol, the last of which doubles as a biomarker for algal growth. In fungal cell membranes the predominant sterol is ergosterol. Bile acids, oxidized derivatives of cholesterol, are synthesized in the liver of mammals.

  A sterol is a steroid with a hydroxyl group at position 3 of the carbon chain. Both share the same fused four-ring core. From that core spring hormones across a series of carbon counts. The C18 steroids include the estrogen family. The C19 steroids are the androgens, such as testosterone and androsterone. The C21 subclass covers the progestogens, glucocorticoids, and mineralocorticoids. The secosteroids, the various forms of vitamin D, are set apart by cleavage of the B ring.

• 5. The Wall Of The Cell

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  Glycerophospholipids are the main structural component of biological membranes. In animal cells, the plasma membrane physically separates the intracellular components from the extracellular environment. Each glycerophospholipid is amphipathic: a glycerol core links to two fatty-acid tails by ester bonds and to one head group by a phosphate ester. Sphingomyelin and sterols, mainly cholesterol in animal membranes, sit alongside them. Plants and algae rely instead on galactosyldiacylglycerols and sulfoquinovosyldiacylglycerol, which lack a phosphate group and crowd the membranes of chloroplasts.

  Plant thylakoid membranes carry the largest lipid component of a non-bilayer forming monogalactosyl diglyceride, and little phospholipid. Despite that unusual recipe, magnetic resonance and electron microscope studies reveal a dynamic lipid-bilayer matrix inside chloroplast thylakoids.

  The hydrophobic effect is what assembles these walls. When glycerophospholipids meet an aqueous environment, forming a lipid bilayer becomes energetically preferred. The polar heads turn toward the water while the nonpolar tails huddle away from it. Water molecules cannot form hydrogen bonds to the lipophilic regions, so they arrange into an ordered clathrate cage around the dissolved molecule. Depending on concentration, the result may be a micelle, a liposome, or a bilayer.

  The formation of lipids into protocell membranes marks a key step in models of abiogenesis, the origin of life.

• 6. Fuel And Messenger

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  The complete oxidation of fatty acids releases about 38 kJ/g, or 9 kcal/g. Carbohydrates and proteins yield only 17 kJ/g, or 4 kcal/g, by comparison. That density is why triglycerides stored in adipose tissue serve as a major energy reserve in both animals and plants. The adipocyte, or fat cell, continuously builds and breaks down triglycerides, with breakdown driven mainly by the hormone-sensitive enzyme lipase. Migratory birds that must fly long distances without eating burn triglycerides to fuel the journey.

  Beta oxidation is the route that breaks fatty acids down, in the mitochondria or peroxisomes, to generate acetyl-CoA. Two-carbon fragments are stripped sequentially from the carboxyl end through dehydrogenation, hydration, and oxidation, then split by thiolysis. The acetyl-CoA feeds the citric acid cycle and the electron transport chain to become ATP, CO2, and H2O. The complete oxidation of the fatty acid palmitate yields 106 ATP.

  Lipid signaling is a vital part of cell signaling, working through G protein-coupled or nuclear receptors. Sphingosine-1-phosphate, derived from ceramide, regulates calcium mobilization, cell growth, and apoptosis. Diacylglycerol and the phosphatidylinositol phosphates drive calcium-mediated activation of protein kinase C. The prostaglandins, fatty-acid derived eicosanoids, take part in inflammation and immunity. Steroid hormones such as estrogen, testosterone, and cortisol modulate reproduction, metabolism, and blood pressure.

  Phosphatidylserine lipids signal for the phagocytosis of apoptotic cells. Normally flippases keep them on the cytosolic side of the membrane. When flippases are inactivated and scramblases activated, the phosphatidylserines appear on the outer face, and other cells recognize the marker and engulf the dying cell.

• 7. What The Body Cannot Make

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  Some essential lipids cannot be synthesized from simple precursors and must come from the diet. The doubly unsaturated linoleic acid and the triply unsaturated alpha-linolenic acid both fall into this group. Both are 18-carbon polyunsaturated fatty acids, differing in the number and position of their double bonds. Linoleic acid is an omega-6 fatty acid; alpha-linolenic acid is an omega-3. Most vegetable oils, including safflower, sunflower, and corn, are rich in linoleic acid. Alpha-linolenic acid lives in green leaves and in seeds, nuts, and legumes such as flax, rapeseed, walnut, and soy. Fish oils carry the longer-chain omega-3 acids eicosapentaenoic acid and docosahexaenoic acid.

  When the body does build fat, it starts from an oversupply of dietary carbohydrate, converting the excess to triglycerides in a process called lipogenesis. Fatty acid synthases polymerize and reduce acetyl-CoA units, extending the acyl chain through cycles that add, reduce, dehydrate, and reduce again. In animals and fungi a single multifunctional protein runs every step, while plant plastids and bacteria use separate enzymes for each. In humans, stearoyl-CoA desaturase-1 turns stearic acid into oleic acid by introducing a double bond.

  Dietary fat is not optional. Some is necessary to absorb the fat-soluble vitamins A, D, E, and K, along with carotenoids. Many studies link omega-3 consumption to benefits for infant development, cancer, cardiovascular disease, and mental illnesses including depression, attention-deficit hyperactivity disorder, and dementia.

  The verdict on fat is not uniformly grim. Consumption of trans fats, such as those in partially hydrogenated vegetable oils, is a well-established risk factor for cardiovascular disease, and improper cooking can turn good fats into trans fats. Yet large studies tell a more measured story. The Women's Health Initiative Dietary Modification Trial followed 49,000 women for eight years and found no link between fat intake and cancer, heart disease, or weight gain. The Nutrition Source, maintained by the department of nutrition at the T. H. Chan School of Public Health at Harvard University, states that the total amount of fat in the diet is not really linked with weight or disease.