Lipids Lipids of Physiologic Significance

BIOMEDICAL IMPORTANCE The lipids The common property – insoluble in water – soluble in nonpolar solvents They are important dietary constituents – high energy value – fat-soluble vitamins – essential fatty acids Fat is stored in adipose tissue

BIOMEDICAL IMPORTANCE Thermal insulator electrical insulators cellular constituents – Membranes Transport – Lipoproteins Lipid biochemistry is necessary – obesity, diabetes mellitus, atherosclerosis, polyunsaturated fatty acids in nutrition and health

Classification Simple lipids – Esters of fatty acids with various alcohols Complex lipids – groups in addition to an alcohol and a fatty acid – Phospholipids Glycerophospholipids Sphingophospholipids – Glycolipids – Other complex lipids Sulfolipids and aminolipids Lipoproteins

Classification Precursor and derived lipids Neutral lipids – acylglycerols (glycerides),cholesterol, and cholesteryl esters

Free fatty Free fatty acids – Saturated -anoic – Unsaturated -enoic 1,2,3,… α, β, γ,… ω or n carbons Δ

Saturated fatty acids

Unsaturated Fatty Acids Monounsaturated Polyunsaturated Eicosanoids – eicosa- (20-carbon) polyenoic fatty acids Prostanoids – Prostaglandins(PGs) – Prostacyclins (PGIs) – Thromboxanes (TXs) Leukotrienes (LTs) Lipoxins (LXs)

Prostaglandins The number of double bonds – PG1, PG2, PG3 Different substituent groups (on ring) – A, B,C,etc

The leukotrienes and lipoxins Lipoxygenase pathway three or four conjugated double bonds Leukotrienes cause bronchoconstriction as well as being potent proinflammatory agents and play a part in asthma

Unsaturated Fatty Acids Geometric isomerism – Cis on the same side – Trans if on opposite sides as a by-product of the saturation of fatty acids ingestion of ruminant fat Significance – Molecular packing in membranes

Unsaturated fatty acids of physiologic and nutritional significance

Structure of some unsaturated fatty acids

Physical and Physiologic Properties of Fatty Acids Chain Length and Degree of Unsaturation – even-numbered-carbon fatty acids – The melting points

TRIACYLGLYCEROLS (TRIGLYCERIDES) THE MAIN STORAGE FORMS OF FATTY ACIDS Mono- and diacylglycerols

PHOSPHOLIPIDS MAIN LIPID CONSTITUENTS OF MEMBRANES derivatives of phosphatidic acid Phosphatidylcholines (Lecithins) the most abundant phospholipids of the cell membrane represent a large proportion of the body’s store of choline

PHOSPHOLIPIDS Surfactant – Dipalmitoyl lecithin respiratory distress syndrome Phosphatidylethanolamine (cephalin) Phosphatidylserine Phosphatidylinositol Cardiolipin

Lysophospholipids

Phospholipids Plasmalogens

Sphingomyelins

GLYCOLIPIDS GLYCOSPHINGOLIPIDS – NERVE TISSUES – CELL MEMBRANE Galactosylceramide – Sulfatide Sulfogalactosylceramide Glucosylceramide – Glycosphingolipid of extraneural tissues

Simple glycosphingolipids Complex glycosphingolipids – Gangliosides Sialic acid The simplest ganglioside found in tissues is G M3 Functions – Receptor, …

STEROIDS Cholesterol – Atherosclerosis – As Precursor Sterol – Has one or more hydroxyl groups and no carbonyl or carboxyl groups

Stereoisomers – “Chair” or a “boat”form – The rings can be either cis or trans – β bonds above the plane of the rings – α bonds bonds attaching groups below

an all-trans configuration between adjacent rings

a cis configuration between rings A and B

Cholesterol Cholesteryl ester

Ergosterol Precursor of Vitamin D

Polyprenoids Synthesized from five-carbon isoprene units Include – Ubiquinone – Dolichol – Vitamins A, D, E, and K, and β-carotene (provitamin A)

LIPID PEROXIDATION A SOURCE OF FREE RADICALS – Lipids exposed to oxygen – deterioration of foods (rancidity) – damage to tissues Cancer, inflammatory diseases, atherosclerosis, and aging – Peroxide formation from fatty acids containing methylene-interrupted double bonds – Antioxidants Vitamin E, Beta-carotene Urate and vitamin C

AMPHIPATHIC LIPIDS Form – Membranes, Micelles, Liposomes, & Emulsions Contain polar groups – Fatty acids, phospholipids, sphingolipids, bile salts, and, to a lesser extent, cholesterol Part of the molecule is hydrophobic, and part is hydrophilic

Micelles – When a critical concentration of these lipids is present in an aqueous medium – Facilitating absorption of lipids Liposomes – Formed by sonicating an amphipathic lipid in an aqueous medium – as carriers of drugs

Emulsions – Much larger particles

Waxes Serve as – Energy Stores and Water Repellents Esters of long-chain (C 14 to C 36 ) saturated and unsaturated fatty acids with long-chain (C 16 to C 30 ) alcohols Their melting points (60 to 100 °C) are generally higher than those of triacylglycerols

Triacontanoylpalmitate, the major component of beeswax