Unit 1- Lipids

Common property of all lipids

• insoluble in H20

Lipids consist of .. and are …

• HC chains and fused rings

• Hydrophobic/ampipathic molecules

• soluble in organic solvents

  • benzene, chloroform, alcohol, etc

Saturated FAs have how many double bonds

• 0

• Basic formula→ CH3-(CH2)N-COOH

  • CH2= methylene

  • COOH= carboxylic acid group

• Normally 4-36 Cs long

  • most biol. relevant forms 12-24 Cs

FAs are weakly

• acidic

  • pKA→ 4.5-5

Are FAs found in cells? Where

• Yes trace amounts are found in cells

• Normally bound to lipid molecules/complexed to carrier like albumin in bloodstream

Nomenclature for saturated FAs

Nomenclature only applies to UNBRANCHED FAs

• Cn:0

Nomenclature for unsaturated FAs

Nomenclature only applies to UNBRANCHED FAs

• Cn:X (cis/trans)-△^y

  • y= position of double bond(s)

  • x> or equal to 1 (double bonds)

Know how to draw FAs from the nomenclature at certain pH’s

• ph> pka then COO- (deprotonated)

• ph<pka COOH (bc lots of H+ floating around)

Most unsaturated CIS FAs are isolated from..

• Biological sources

FAs with trans double bonds can be produced by

• Ruminants (cows, sheep, etc)→ possess bacteria that can produce trans unsaturated FAs via fermentation

• Industrial hydrogenation of unsaturated FAS

  • Hydrogenation involves adding H2 across double bond

  • ex) making margarine

How to number the omega in unsaturated FAs

• From the terminal carbon

  • so COOH takes priority in chain =1 then keep counting down chain

• Omega-# (where the number is the 1st double bond position from that end tail)

An imbalane of omega__ and omega __ PUFAs is correlated with

• Omega-6 and omega-3

• correlated with increased risk of cardiovascular disease

• Optimal dietary ratio (omega 6-3)

  • 1:1-4:1

  • in NA it’s 10:1-30:1

• get omega-3 FAs from

  • leafy veggies, flax seeds, veg oils

  • Fish like salmon cod and tuna

As number of Cs increases what happens to Tm (melting temp) and why?

• Tm increases as C # increases because VDWs increases as there’s tighter packing so more forces holding them together

• so Tm increases

As double bonds incorporated what happens to Tm and why?

• Tm decreases when double bonds added bc this puts kinks in the chain and leads to less tight packing, decreases VDW, decreases Tm (easier to break apart)

Overall Tm trend

• Saturated FAs> Unsat Trans FA> Unsat Cis FA

Phytol= long chain alcohol that when consumed→ phytanic acid. Refsum’s disease= neuro disorder related to phytanic acid accumulating in nerve cell membranes.

What general effects of phytanic acid on these membranes would be observed?

• When phytanic acid incorporated into membranes Tm decreases bc less packing(as its branched) and this decreases VDW

• Phytanic acid liquifies myelin sheath due to decreased VDW so poor communication

How are micelles formed?

• when free FAs enter aq soln they can form micelles

• If the cross sectional area of A (ball)> B (tail) then free FA takes on a cone-shaped structure→ micelles formed

  • FA with 1 tail basically

  • ex) C20:0, lyso___

TAGs (triaglycerols)- neutral fats are derived from?

• glycerol backbone

• Very reduced

• Have 3 FAs attached to 1 glycerol with ester linkage

be able to draw and recognize structure

Functions of TAGs

• Used mainly for energy storage (fuel)

• TAGs stored in special fat cells called adipocytes→ TAGs in adipose tissues can be used for insulation @ cold temps

• C’s most reduced compared to carbs + proteins

  • when oxidized TAGs yield MORE energy (FA’s- 9kcal/g, carbs/proteins= 4kcal/g)

• (the glycerol can enter GNG→ DHAP→ glucose)

How do TAGs reduce water weight?

• TAGs very hydrophobic + carry less H20 weight than polysaccharides

• TAGs come together into dense droplets

Based on structure of TAGs why can this structure NOT form micelles even though FAs are a major component of TAGs? Why are TAGs not a major component of cell mebranes?

• The cross sectional areas of A + B are similar so won’t form a micelle

  • like a cylinder

• Not part of membrane bc lack a polar head (not ampihpathic) needed to form lipid bilayer

Biological waxes structure

• consist of long chain alcohol + FA that are linked together via ester bond (C=O-O)

• Have high Tm

• ex) candies, car wax etc

  

recognize structure of wax

Generalized phospholipid structure be able to draw and recognize

NEXT moving on from storage lipids to STRUCTURAL LIPIDS

→Glycerophospholipids basic structure

• Head group(charged)-glycerol backbone- 2 fatty acyl chains

FA-C1 (ester linkage)

FA-C2 (ester linkage)

. -C3-P-alcohol (polar head group)

• Phosphoester linkages

ABUNDANT in membranes

Glycerophospholipids are amphipathic meaning?

• the molecule has a distinct polar end and np end

If head group (X)= H then what is it?

• phosphatidic acid

• net charge=-1 (-1 from the phosphate)

Recognize head group

• Ethanolamine

• Full lipid name→ phosphatidylethanolamine (PE)

• Net charge-0

  • zwitterionic (neutral molecule with positive and negative charge)

Phosphatidylglycerol (PG)

• net charge:-1

• choline (phospatidylcholine PC)

• net charge:0

  • zwitterionic (neutral molecule with positive and negative charge)

Phosphatidylserine (serine)

• Net charge: -1

• phosphatidylinositol (inositol)

• net charge: -1

PL (phosphilip) aggregates form a BILAYER structure to..

• minimize interactions of FA chains (NP) with H20 (polar)

• If cross sectional area of A (ball head)=B (NP FA chains) then glycerophospolipid will form bilayer structures

Phospholipases are

• hydrolytic enzymes

• cut (hydrolyze) glycerophospholipids

• Phospholipase A (1 or 2 ) cut 1 of the FA chains→ lysophospholipid + free FA

• PL C and D are phosphodiesterases

  • PLC→ DAG + phospho__(head group)

  • PLD→ phosphaditic acid + head group X

Why do lysoPL form micelles instead of bilayer structures?

• Because lysoPL have 1 FA cut off the chain→ this forms a micelle bc A cross section > B (forms cone in aq envt→ micelles)

  • thus, lyses cells (no cell membrane intact bc no bilayer formed)

• PC + H20→ Lyso-PC + free FA

. A2

Friend bitten by snake almost dying from hemolysis (rbc breaking). Why is phospholipase A1 in the venom responsible for rbc hemolysis?

• Phospholipids + H20→ lysoPL + Free FA

. A1

• Problem because rbcs burst as micelles form instead of bilayer (lyses cells)

Sphingosine backbone

• look for ONO

Ceramide

• When X=H on O of C1

• FA attached in AMIDE LINKAGE w/ NH2

Sphingomyelin

• When X= phosphocholine/ phosphoethanolamine on C1’s oxygen

• Part of myelin sheath that surr and isnulates axons of some neurons

• ONLY cell membrane PL in humans not derived from glycerol

Glycosphingolipids

• Cerebrosides

• 1 sugar (galactose/glucose) linked to C1’s oxygen in ceramide

• GALACTOSE attached

  • found in membranes of cells in neural tissues

• GLUCOSE

  • found in membranes of cells in non-neural tissues

(neutral no charge at ph 7)

Glycosphingolipids

• globosides

• X=2 or more sugar monomers on C1 oxygen in ceramide

Glycosphingolipids

• Gangliosides

• X= 3 or more sugar monomers on C1’s oxygen in ceramide

  • 1 of the sugar monomers MUST BE N-acetylneuraminic acid (Neu5Ac/sialic acid)

  • each of this monomer gives the ganglisode a -1 charge at neutral pH

Neu5Ac structure in ganglioside

Cholestrol structure

• 4 fused rings

  • 3 with 6 C’s: 1 w/ 5C’s

• Planar and rigid

• Amphipathic

• Precursor for steroid hormones

• bile acids= polar derivates of cholestrol

Eicosanoids are ___ and derived from___

• signaling lipids derived from arachidonic acid (FA is c20:4 cis-triangle(5,8,11,14)

• Act as paracrine hormones (= short range acting hormone)

• Arachidonate then leads to formation of..

  • Prostaglandins → in response to tissue injury, cause pain response

  • Thromboxane→ produced by platelets, induce formation of blood clots

    • NSAIDS work on them

  • Leukotriene→ causes contraction of smooth muscle lining lung airways, overproduction= asthma attack

Why are Aspirin/Ibuprofen (NSAIDS) “non steroidal”

• they lack 4 fused rings and arent steroids

Steroid hormones exs

• Estrogen and testosterone

• Steroid hormones are derived from cholestrol

• carry messages bw tissues

Lipid soluble vitamins exs

• Vitamin K and E

  • important for blood clotting

  • aids in producing prothrombin which is used to make fibrin (a insoluble fibrous protein)

  • need to get from diet

Fibrin is a protein that

• holds blood clots together

• acts as biological antioxidants

• helps in preventing oxidative damage to membrane lipids

When drawing a FA at different pH’s when to put a COO- or COOH

• ph> pka then COO- (deprotanated)

• ph<pka then COOH (bc have lots of H+, fx group picks up and we get the protonated form)

• pka~4.5