Lipid Chemistry: Structure, Types and biomedical importance

Lipid Chemistry Basics

• Lipids are a varied group of organic compounds linked to fatty acids.
• Lipids contain carbon, hydrogen and oxygen.
• Some lipids can contain phosphorus, nitrogen and sulfur.
• Lipids are relatively insoluble in water.
• Lipids are Soluble in nonpolar solvents like ether, chloroform, benzene, and acetone, which are used to extract them from cells.
• Living organisms utilize lipids.
• Lipids contain or are derived from fatty acids.

Biomedical Importance of Lipids

• Lipids have a high caloric energy value of 9.3 KCal/g when fat is oxidized
• Fats as efficient energy sources when stored in adipose tissues
• Lipids are dietary constituents because of fat-soluble vitamins and essential fatty acids
• Lipids serve as protective coatings for many organisms and organs.
• Lipids act as thermal insulators in subcutaneous tissues.
• Lipids serve as electrical insulators in myelinated nerves.
• Lipids serve as important cell surface components.
• Fat and protein combinations (lipoproteins) are important cellular elements in cell membranes and mitochondria in the cytoplasm.
• Lipoproteins transport lipids in blood.
• Lipid biochemistry knowledge helps to understand areas of interest like obesity and atherosclerosis.
• Lipid biochemistry knowledge helps to understand the role of polyunsaturated fatty acids in nutrition and health.

Lipid Classification

• Lipids are classified into simple, complex and derived lipids.

Simple Lipids

• Simple lipids include true fats and waxes.
• True fats are esters of fatty acids with glycerol (acylglycerols).
• Waxes are esters of fatty acids with higher molecular weight alcohol.

Complex Lipids (Compound Lipids)

• Complex lipids are esters of fatty acids with alcohol & contain another group like phosphate, carbohydrate, sulfate, or protein.
• Phospholipids contain fatty acid, alcohol, and phosphoric acid, and often an alcoholic base, and are a type of complex lipid.
• Glycerophospholipids contain glycerol as the alcohol.
• Sphingophospholipids contain sphingosine as the alcohol.
• Glycolipids (Glycosphingolipids) contain carbohydrates, and are a type of complex lipid.
• Lipoproteins contain lipids and proteins, and are a type of complex lipid.

Derived Lipids

• Derived lipids are either from simple and compound lipids or are associated with lipids.
• Derived lipids include fatty acids, glycerol, alcohols (other than glycerol), steroids, carotenoids and fat-soluble vitamins like Vitamins A, D, E, and K.

Simple Lipids: True Fats (Neutral fats)

• True fats are esters of glycerol and various fatty acids.
• If all three hydroxyl groups of glycerol are esterified, they are triacylglycerols (triglycerides).
• The three linked fatty acids linked to glycerol are typically different.

Glycerol

• Glycerol is a trihydric alcohol containing three hydroxyl groups, is colorless, syrupy, sweet, and viscous.

Fatty Acids

• Fatty acids are aliphatic monocarboxylic organic acids.
• Fatty acids are mostly obtained from natural fats and oils hydrolysis.
• Fatty acids in natural fats contain an even number of carbon atoms, range from 2-24 carbons, and have a long hydrocarbon chain & terminal carboxyl group.

Fatty Acid Classification by Chain Length

• Short-chain fatty acids contain from 2-10 carbon atoms with examples like:
  • Acetic acid (2 C): CH3-COOH
  • Butyric acid (4 C): CH3-CH2-CH2-COOH
  • Caproic (6 C): CH3-(CH2)4-COOH
  • Octanic acid (8C): CH3 -(CH2 )6 - COOH
• Long chain fatty acids contain more than 10 carbon atoms, examples like
  • Palmitic (16 C): CH3-(CH2)14-COOH
  • Stearic (18 C): CH3-(CH2)16-COOH
  • Arachidic (20 C): CH3-(CH2)18-COOH
  • Oleic acid (18 C) (unsaturated): CH3-(CH2)7-CH = CH-(CH2)7-COOH

Fatty Acid Classification by Saturation

• Saturated fatty acids contain no double bonds.
  • Examples include Butyric fatty acid, Caproic, Palmitic, and Stearic.
• Unsaturated fatty acids contain one or more double bonds.
  • Monounsaturated fatty acids contain one double bond.
    • Oleic acid is an example: ω 9 18: 1; 9. CH3-(CH2)7-HC = CH-(CH2)7-COOH
  • Polyunsaturated fatty acids contain more than one double bond.
    • Double bonds are usually separated by methylene groups (-CH2-).
    • Linoleic 18: 2; 9, 12: (ω 6) is an example: CH3-(CH2)4-CH = CH-CH2-CH = CH-(CH2)7-COOH
    • α-Linolenic 18: 3; 9 12, 15: ( ω 3) is an example: CH3-CH2-CH=CH-CH2-CH=CH-CH2-CH = CH(CH2)7-COOH
    • Arachidonic: 20: 4; 5, 8, 11, 14: (ω 6) is an example: CH3-(CH2)3-(CH2-CH = CH)4 – (CH2)3-COOH
    • Arachidonic acid, 20:4; 5, 8, 11, 14: (ω 6), is a precursor to prostaglandins.

Fatty Acid Classification by Biological Importance

• Essential fatty acids are polyunsaturated with more than one double bond, are Linoleic(ω6), and Linolenic(ω3).
• Mammals cannot synthesize Linoleic and linolenic, thus these must be obtained from plant sources.
• Non-essential fatty acids are saturated or contain one double bond, and mammals can synthesize them from other precursors.
• Relatively essential is Arachidonic acid (ω6).
• Arachidonic acid found in diet (animal fats and peanut oil) and synthesized in the body from linoleic acid.
• Arachidonic becomes essential if its precursor (linoleic acid) is missing in the diet.

Types of Acylglycerols

• Monoacylglycerol: Esters of one fatty acid with glycerol.
• Diacyl glycerol: Esters of two fatty acids with glycerol.
• Triacylglycerol: Esters of three fatty acids with glycerol.

Biological Importance of Acylglycerols (True fats)

• Acylglycerols form reserve/storage foods in animals and plants.
• In animals, acylglycerols are depot fat in subcutaneous tissues and mobilized during starvation, making it a variable element of fat.
• Acylglycerols are the most compact form in which energy can be stored, where 1 gm of fat gives 9.3 KCal.
• Acylglycerols are also found as supporting material around the kidneys.

Complex lipids: Phospholipids

• Phospholipids are amphipathic with polar and nonpolar groups, making them ionic compounds.
• Two classes of phospholipids:
  • Glycerol-based (Glycerophospholipids)
  • Sphingosine-based (Sphingophospholipids)

Glycerophospholipids (phosphoglyceride)

• The precursor compound of glycerophospholipids is glycerol-3-phosphate.
• This compound has an asymmetric carbon atom, existing in D or L form, where the L-isomer of glycerol phosphate is found in natural phosphoglycerols.
• Phosphoryl bases are polar, hydrophilic heads with hydrocarbon hydrophobic tails and are present in phosphoglycerols.
• Pure phosphoglycerols are white solids that darken on air exposure due to chemical changes in polyunsaturated fatty acids (Peroxidation).
• Phosphoglycerols are soluble in most nonpolar solvents, best extracted by chloroform methanol mixtures, and not very soluble in acetone.
• Phospholipids exhibit hydrotropic properties and transport fatty substances across the intestinal mucosa.
• Amphipathic lipids disperse in water, forming aggregates like micelles when phosphoglycerol is added.
• In micelle structures, hydrocarbon tails are hidden from water, forming an internal hydrophobic phase and hydrophilic heads exposed on the surface.
• Glycerophospholipids are widely distributed, especially in nerves and cell membranes which control cell permeability.
• The amount of glycerophospholipids remains constant even in starvation (constant element of fat).

Derived Lipids Include

• Fatty acids
• Glycerol
• Alcohols (other than glycerol)
• Steroids
• Carotenoids
• Fat Soluble vitamins

Steroids

• Steroids have a similar cyclic nucleus known as the steroid nucleus.
• Steroids include sterols, bile acids and salts, steroid hormones, and Vitamin D.

Cholesterol (Animal Sterol)

• Cholesterol is the main sterol in the human body found in nervous tissue, brain, suprarenal gland, and bile.
• Cholesterol is present in blood at a normal level of 150-200 mg/dl, often as cholesterol ester combined with fatty acids.
• Fatty acids in Cholesterol is attached to the hydroxyl group.
• Cholesterol is a major plasma membrane constituent and in precursor of sex hormones, cortical hormones, vitamin D, and bile acids.
• Cholesterol is formed in the body from acetyl CoA and present in animal fats like egg yolk, meat, liver, and brain, but not in plant fats.
• High blood cholesterol leads to atherosclerosis and gallstones.

Cholesterol Derivatives

• 7-dehydrocholesterol (Provitamin D3) is stored under the skin and transformed into cholecalciferol (vitamin D3) by ultraviolet rays (sunlight).
• Bile acids are obtained in the liver by cholesterol oxidation at C24 with removal of the last three carbon atoms.
• Bile acids are the end products of cholesterol catabolism since the steroid nucleus is not broken down by the body.
• Bile salts are products of primary bile acids conjugated with glycine or taurine in sodium or potassium salts.
• Sodium/potassium glycocholate and sodium/potassium taurocholate are examples of Bile salts.
• Bile salt functions include activating pancreatic lipase, emulsifying and hydrotropic action by decreasing surface tension and increasing surface area for better lipid digestion and absorption.
• Bile salts facilitate the absorption of fat-soluble vitamins and fatty acids.