Biochemistry - Lipid Structure and Function

Chapter 5

Lipids class characterized by

- insolubility in water
- solubility in nonpolar organic solvents

lipids

major component of phospholipid bilayer (one of the most important structural parts of cell)

phospholipid bilayer

allows cells to function as they do; separate cell interior from surrounding environment

amphipathic molecule

- each of membrane components have hydrophobic (fatty acid tails) and hydrophilic (polar head) regions

formation of liposomes, micelles, & phospholipid bilayer

in aqueous solution, molecules spontaneously form structures (hydrophobic regions group internally & hydrophilic regions interact with water)

phospholipid

contains phosphate & alcohol (polar head group), hydrophobic fatty acid tail [connected via phosphodiester linkages]
- further classified according to backbone on which molecule is built (example: glycerol)

glycerol

3-carbon alcohol that forms phosphoglycerides & glycerophospholipids

Properties that determine molecule behavior

- length of hydrocarbon chain
- degree of saturation

saturated fatty acids

- only single bonds
- carbon atom is saturated when bonded to 4 other atoms (w/o pi bonds)
- have greater var der Waals forces
- more stable overall structure
- form solids at room temp

unsaturated fatty acids

- includes 1 or more double bonds
= kinks in fatty acid chain
= difficult to stack and solidify
- liquids at room temp

Glycerophospholipids (phosphoglycerides)

- type of phospholipid
- glycerol backbone bonded by ester linkage to two fatty acids & phosphodiester linkage to highly polar head group
[head group: determines membrane surface properties, can be neg/pos/neutral charge]
[membrane surface properties = imporant to cell recognition, signaling, binding]
[w/in each subtype: fatty acid chains vary in length/saturation = variety of functions]

phosphatidylcholine

glycerophospholipid with choline head group

phosphatidylethanolamine

glycerophospholipid with ethanol-amine head group

Sphingolipids

- sphingosine/sphingoid backbone
- long chain, nonpolar fatty acids tails, polar head group
- many sphingolipids are phospholipids (contain phosphodiester linkage); others contain glycosidic linkages to sugars (glycolipid)

sphingolipid subclasses (based on head group)

ceramide
sphingomyelins
glycosphingolipids (glycolipids)
gangliosides

ceramide

- simplest sphingolipid
- single hydrogen head group

sphingomyelin

- major class of sphingolipids that are also sphingophospholipids
- either phosphocholine/phosphoethanolamine head group (no net charge) = phosphodiester bond
- major components in plasma membranes of cells (oligodendrocytes & schwann) producing myelin (insulating sheath for axons)

glycosphingolipids (glycolipids)

- sphingolipids with sugars bonded by glycosidic linkages head group
- not phospholipids; don’t contain phosphodiester linkage
- found on outer surface of plasma membrane; further classify into cerebrosides & globosides
- cerebrosides & globosides (neutral glycolipids ~no net charge at physiological pH)

cerebrosides

have single sugar

globosides

have two or more sugars

gangliosides

- composed of most complex sphingolipids
- glycolipids with polar head groups of oligosaccharide with 1 or more N-acetylneuraminic acid (NANA; sialic acid) molecules at terminus & negative charge
- glycolipid; glycosidic linkage, no phosphate group
- major role in cell interaction, recognition, signal transduction

Waxes

- esters of long-chain fatty acids with long-chain alcohols
- form pliable solids at room temp
- function as protection for plants (secreted as surface coating = prevents evaporation & protects against parasites) & animals (secreted to prevent dehydration, water-repellant to keep skin/feathers dry, lubricant)

wax examples

- carnauba wax: made from leaves of Copernica prunifera palm, used to coat candles and wax cars
- beeswax: secreted by bees to construct shelter

3 categories of signaling lipids

steroids
protaglandins
fat-soluble vitamins
(+ terpene precursors)

Terpenes & Terpenoids

- odiferous chemicals that have varied independent functions
- metabolic precursors to steroids & other lipid signaling molecules

Terpenes

- class of lipids built from isoprene (C₅H₈) moieties
- share common structural pattern with carbons grouped in multiples of 5
- produced by plants & insects (part of their protective mechanism)
- strong scent (primary component of pleasant smells)
- grouped based on number of isoprene units present

Monoterpene (single terpene unit)

2 isoprene units; abundant in both essential oils and turpentine

Sesquiterpene

3 isoprene units; sesqui = one-and-a-half

Diterpene

4 isoprene units; Vitamin A = retinal (visual pigment for sight) is derived

Triterpene

6 isoprene units; can convert to cholesterol & various steroids

Tetraterpenes (carotenoids)

(B-carotene & lutein)
8 isoprene units

Polyterpene

between 1000 and 5000 isoprene unit chain

Terpenoids (isoprenoids)

- derivatives of terpenes that have undergone oxygenation/rearrangement of carbon skeleton
> further modified by addition of extensive variety of functional groups
- share similar characteristics with terpenes (biological precursor function & aromatic properties = contribute to steroid biosynthesis & scents of cinnamon/eucalyptus/camphor/turmeric/etc)
- named in analogous fashion (example: diterpenoids = 4 units)

Steroids

- metabolic derivatives of terpenes
- 4 cycloalkane rings fused: 3 cyclohexane + 1 cyclopentane
- functionality determined by oxidation status of rings & functional groups carried
- large number of carbons & hydrogens = nonpolar steroids

Steroid hormones

• steroids that act as hormones:
  - secreted by endocrine glands into bloodstream
  - travel on protein carriers to distant sites
  - bind to specific high-affinity receptors
  - alter gene expression levels

• potent biological signals that regulate gene expression and metabolism = affect biological systems even at low concentrations

Cholesterol

- steroid of primary importance; major component of phospholipid bilayer & responsible for mediating membrane fluidity
- amphipathic molecule containing hydrophilic & hydrophobic components
- hydrophobic tails & hydrophilic tails allow cholesterol to maintain constant fluidity in cell membranes (low temp: prevents membrane solidifying) (high temp: prevents increased permeability)
- precursor to many molecules (steroid hormones, bile acids, Vit D)

Prostaglandins

- produced by almost all cells in body, act as paracrine/autocrine signaling molecules
- 20-carbon molecules; unsaturated carboxylic acids derived from arachidonic acid, contain one 5-carbon ring
- regulate synthesis of cyclic adenosine monophosphate (cAMP)
= cAMP mediates actions of other hormones
- affects smooth muscle function, influence over sleep-wake cycle, elevation of body temp (fever/pain)

cyclooxygenase (COX)

- aids in production of prostaglandins
- inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin

Fat-soluble Vitamins

- essential nutrient that can’t be adequately synthesized by body
= consumed in diet
- divided into water-soluble and lipid-soluble
- include vitamins A, D, E, K (important/varied functions)

water-soluble vitamins

excreted through urine

lipid-soluble vitamins

accumulate in stored fat

Vitamin A (carotene)

- unsaturated hydrocarbon
- important in vision, growth/development, immune function
- retinal (aldehyde form): most significant metabolite of vit A & component of light-sensing molecular system in human eye
- retinol: storage form of vit A, oxidized to retinoic acid, hormone regulating gene expression during epithelial development

Vitamin D (cholecalciferol)

- consumed/formed in UV light-driven reaction in skin
- converted to calcitrol (active form) in kidneys & liver
= increased calcium & phosphate uptake in intestines
= promotes bone production

Vitamin E

- group of closely related lipids (tocopherols & tocotrienols)
- t & t: hydrophobic substituted aromatic ring with long isoprenoid side chain
- tocopherols: biological antioxidants
- aromatic rings react with and destroys free radicals
= prevents oxidative damage (important contributor to cancer/aging development)

Vitamin K

- group of compounds: phylloquinone (K₁) & menaquinones (K₂)
- vital to posttranslational modifications to form prothrombin (important clotting factor in blood)
- aromatic ring undergoes oxidation & reduction cycle during prothrombin formation
- introduces calcium-binding sites on several calcium-dependent proteins

lack of Vit D

results in rickets; (condition in children) underdeveloped, curved long bones & impeded growth

Triaglycerols

- class of lipids for energy storage & insulation (retains body heat to reduce energy needed for maintaining constant internal temp)

Why lipids are good for storing energy

1- carbon atoms of fatty acids are more reduced (than those of sugars)
= oxidation of triacylglycerols yields x2 amount of energy per gram as carbs
2- triacylglycerols are hydrophobic (don’t draw in water nor require hydration for stability)
= helps decrease weight

Triaglycerol (triglyceride) compound

- 3 fatty acids bonded by ester linkages to glycerol
- physical characteristics determined by saturation/unsaturation of fatty acid chains
- nonpolar & hydrophobic
> contribute to insolubility in water: polar hydroxyl group of glycerol bond to polar carboxylate of fatty acid
= decreased polarity

Triaglycerol deposits

- observed in cells as oily droplets in cytosol
= depots of metabolic feul (recruited when cell needs additional energy to divide/survive when other fuel supplies are low)
- found in seeds as oils
- travel bidirectionally in bloodstream between liver & adipose tissue

Adipocytes

- special cells in animals that store large amounts of fat
- found under skin, around mammary glands, in abdominal cavity

Free fatty acids

- unesterified fatty acids with free carboxylate group
- circulate in blood bonded noncovalently to serum albumin
- make up soap (by saponification)

Saponification

ester hydrolysis of triacylglycerols using a strong base (lye ~sodium or potassium hydroxide)
= cleavage of fatty acid
= leaves sodium salt of fatty acid and glycerol
= fatty acid salt is soap

Surfactant

- lowers surface tension at surface of liquid = detergent or emulsifier
- soaps can act as surfactants: can combine separate phases (vinegar + olive oil)

Colloid

formed by combinding 2 phases (vinegar + olive oil)

Micelles

- tiny aggregates of soap with hydrophobic tails turned inward & hydrophilic heads turned outward
= shields hydrophobic lipid tails
= allows overall solvation
- absorbs fat-soluble vitamins (A, D, E, K) & complicated lipids (lecithins)
- fatty acids & bile salts form micelles
= increases surface area for lipolytic enzymes

Nonpolar compounds

- can dissolve in hydrophobic interior of water-soluble micelle
= cleaning agents can dissolve both water-soluble/insoluble (all washes away together)