GUTS Session on Lipid Structure & Nomenclature Get UP To Speed (GUTS) Session on Lipids A primer on lipid structure, nomenclature, and function See also the GUTS session on Lipids notes (.doc) - self-assessment exam - additional lipid information Dr. Arrel Toews (say Tavz, like “waves”) 420 ME Jones Building atoews@med.unc.edu 843-8727

Lipids Definition: biomolecules that are overall hydrophobic - very non-polar - insoluble in water/aqueous solutions (cellular environment) - soluble in “organic” (non-polar) solvents (CHCl3-MeOH) - operational rather than structural definition (water-fearing) - contrast this with definitions for: proteins nucleic acids carbohydrates

Lipid Functions - energy source (dietary triglycerides) - energy stores (adipose tissue triglycerides) - triglycerides are completely hydrophobic highly reduced (energy-rich) compact, efficient energy storage - membranes – amphipathic lipids (both hydrophobic and hydrophilic portions) - phospholipids - sphingolipids - cholesterol - signaling molecules 2nd messenger systems; eicosanoids; steroid hormones - fat-soluble vitamins: A (vision), D (bones/teeth), E (anti-oxidant; live forever), K (blood clotting) Fatty acids are basic building block of most lipids

Structure and nomenclature of fatty acids Long-chain carboxylic acids; building blocks of most lipids H H H H H H H H H H H H H H H H H O l l l l l l l l l l l l l l l l l ll H―C―C―C―C―C―C―C―C―C―C―C―C―C―C―C―C―C―C-O- l l l l l l l l l l l l l l l l l H H H H H H H H H H H H H H H H H * O ll CH3CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2C-O- * O ll C-O- * Stearic acid CH3(CH2)16COOH Systematic: octadecanoic acid Shorthand: 18:0 (18C, no double bonds) *All fatty acids ionized at physiological pH; pKa <5

Structure and nomenclature of fatty acids Linoleic acid CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH Systematic: cis, cis 9,12-octadecadienoic acid Shorthand: 18:26 This is shorthand for a fatty acid with 18 carbons and 2 double bonds. The 6 indicates the double bond closest to the methyl end is 6 carbons from the  end. If more than one double bond, the configuration is always “methylene-interrupted” (-CH=CH-CH2-CH=CH-) with cis double bonds. Always 3C between C=C bonds So - the term 18:26 completely defines the formula and structure of linoleic acid

Structure and nomenclature of fatty acids   “biochemists” O ll CH3―(CH2)n―CH2―CH―C-O-  no matter how long generic fatty acid 18 or whatever 3 2 1 “systematic” -designation important in nomenclature “-oxidation” of fatty acids CH3(CH2)14COOH CH3(CH2)5CH=CH(CH2)7COOH CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH CH3(CH2)CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)2COOH Try this at home: write shorthand names for the FA below Write the chemical formulas for 18:19 and 20:53

Fatty Acids: long-chain carboxylic acids COOH 3 HC H cis-fatty acid trans - fatty acid saturated fatty acid O ll *really C―O- usually attached to glycerol as PL or TG Virtually all natural C=C double bonds are cis “kinks” – less packing – more fluid GOOD for membranes trans-FA are BAD! – no kinks, pack tightly;  LDL;  HDL (partially hydrogenated vegetable oils, Crisco, margarine)

Physiological functions of lipids – a problem hydrophobicity (long chain length) and fluidity (liquid at body temperature) both vital required biophysical properties - cell membranes - storage depots of energy (adipose tissue) But melting point increases with chain length So FA long enough to be hydrophobic are solids! (mp is above body temp) How does Mother Nature handle this??

Melting points of fatty acids 90 18C fatty acids 80 70 Saturated fatty acids Stearic acid (18:0) 60 50 40 Body temperature Melting temperature (°C) 30 20 Oleic acid (18:1) 10 18:4 -57C Linoleic acid (18:2) -10 — Linolenic acid (18:3) -20 2 4 6 8 10 12 14 16 18 20 22 24 Number of carbon atoms

Physiological functions of lipids The fatty acid composition of membrane lipids and adipose tissue triglycerides - chain length - degree of unsaturation is carefully regulated to maintain the appropriate fluidity

Most of the fatty acid in the body is esterified – much of it as triglyceride (mostly in adipose tissue) – also lots in phospholipids (major components of membranes) Fatty acid composition is regulated to maintain correct fluidity (both TG and PL) - critical to biological function O ll CH2OC fatty acid glycerol O ll CHO C Triglyceride energy source storage form O ll CH2OC

Phospholipids – vital components of membranes glycerol backbone (like TG) - 2 FA in ester linkages - phosphate + X (choline, ethanolamine, serine, inositol) amphipathic (amphi = both) polar head long hydrophobic tail e.g., choline+ F A T T Y A C I D GLYCEROL F A T T Y A C I D Remember kinks in cis-double bonds of unsat’d FA P THE defining components of biological membranes - make lipid bilayers (2 molecules thick)

Phosphatidylcholine (PC) aka lecithin a prominent phospholipid major membrane component involved in cholesterol handling too glycerol 2 long-chain fatty acids Choline (polar “X”) phosphate FA heterogeneity means many molecular species of PC

2nd messenger signaling systems O ll CH 2 - C fatty acid P l 3 HN + ethanolamine Phosphatidylethanolamine (PE) membranes 2nd messenger signaling systems

(more on these in “Complex CH2O” GUTS session) Sphingolipids Structures and properties are generally similar to phospholipids (amphipathic) Phospholipids long hydrophobic tail polar head sugar(s) O Long-chain amino alcohol (sphingosine) Glycosphingolipids (usually) F A T T Y A C I D (more on these in “Complex CH2O” GUTS session)

Hydrophobic tails hide from water Amphipathic nature of PL and sphingolipids is vital to life; makes membranes water Lipid bilayer water Polar head Micelle Hydro- phobic tail Phospholipid or glycolipid Hydrophobic tails hide from water Lots more on this in Dr. Jacobson’s Membranes GUTS lecture

Cholesterol - rigid ring structure - “a little bit” amphipathic polar - “a little bit” amphipathic Cholesterol - rigid ring structure - membrane component (affects fluidity) - lipid transport in blood (atherosclerosis, &c)

Vocabulary – do you know the meaning of the following terms? lipid hydrophobic vs hydrophilic amphipathic fatty acid saturated vs unsaturated FA cis vs trans C=C double bonds shorthand nomenclature for FA triglyceride (and mono- and diglyceride) phospholipid sphingolipid cholesterol