Lipids And Membranes 13

Question 1

Lipid association

Answer 1

• lipids are heterogenous, hydrophobic (or amphipathic), and thus insoluble
• lipids associate into larger structures are not usually free in solution (due to hydrophobic effect)
• due to potential at aggregate, their storage and transport is a challenge

Question 2

Lipid classification

Answer 2

• Fatty acids: FAs aliphatic carboxylic acids
• Triacylglycerolds: TAGs have 3 FAs es terrified to glycerol
• Phospholipids: PLs have phospho head group attached to diaglycerol or ceramide
• Isoprenoids/Steroid: cholesterol
• Glycolipids: gylcosphingolipids

Question 3

Fatty acids

Answer 3

• amphipathic: have hydrophilic carboxyl group and a hydrophobic hydrocarbon tail of variable length
• may be saturated (no double bonds), mono- or poly-unsaturated: double bond position are specified either from COOH end or from tail (omega)
• most natural unsaturated FAs have unconjugated cis double bonds
• unconjugated: not present at every other double bond

Question 4

Diversity of fatty acids

Answer 4

• some essential FAs must be obtained from the diet… we can make the rest
• in humans most FAs are found es terrified to cholesterol or glycerol, or are bound to albumin in the blood

Question 5

Nomenclature for FA double bonds

Answer 5

1. Count carbons starting from carboxyl group: list positions of the double bonds, assuming cis unless otherwise specified
2. Count the carbons starting from the tail to the first double bond (tail carbon referred to as omega)

Question 6

Fatty acid derivatives

Answer 6

• arachidonic acid (20:4) is the precursor of eicosanoids: bioactive FAs including prostaglandins and thromboxanes (from COX enzymes), and leukotrienes
• soaps are Na+ salts of FAs
• Waxes consist of FAs es terrified to long chain alcohols

Question 7

Triacylglycerols

Answer 7

• consist of 3 FAs esterified to glycerol
• found in circulating lipoproteins or in insoluble cytosolic lipid droplets
• in adipose tissue, stored TAG in droplets can be hydrolyzed to release FFA and glycerol for delivery to the liver and other tissues
• TAGs are the major energy reserve in the body: oxidation of FAs produce over twice the energy per gram compared to carbohydrates

Question 8

Lipoproteins

Answer 8

• allows for triacylglycerol transport
• TAGs are packaged as lipoproteins when in circulation to allow for transport
• TAG in lipoproteins are delivered in the blood to peripheral tissues as a fuel source, or for storage in adipose tissue

Question 9

Glycerophospholipids

Answer 9

• most phospholipids are esters of 3-glycerophosphate, 2 FAs and a polar head group
• Lyso-PLs have only one FA
• headgroups vary by charge, cellular location, and effects on membrane curvature and protein function (phophatidylcholine is the most abundant)
• The most important role of PL is as a major component of cellular membranes and vesicles
• PLs are also precursors of lipid second messengers: position specific cleavage of PIP2 by phospholipases generates bioactive molecules

Question 10

Sphingomyelin and Glycospingolipids

Answer 10

• both contains a sphingosine backbone

- have signalling recognition roles and are abundant in the brain

Question 11

Genetic disorders of glycosphingolipid degradation

Answer 11

• GSLs are synthesized and degraded in strictly ordered pathways: genetic defects in lysosomal GSL degradation causes severe neurodegenerative diseases:
  
  • Tay-Sachs disease
  • Gaucherie disease
  • Metachromatic leukodystrophy
  • Krabbe disease
  • Gangliosidosis
  • Sandhoff disease
  • Fabry Disease
  • Niemann-pick disease
  • Farmer Disease

Question 12

Cholesterol and isoprenoids

Answer 12

• cholesterol plays an important structural role in maintaining lipid bilateral fluidity, derived from diet or made endogenously from isoprene
• cholesterol is highly insoluble and must be transported in lipoproteins, imbalances in which cause antherosclerosis and vascular diseases
• the liver coordinates intercellular transport and regulation of cholesterol
• in humans cholesterol is excreted, not degraded

Question 13

Cholesterol derivated

Answer 13

• precursor of bile acids, steroid hormones and vitamin D

- isoprenoids (derived from cholesterol intermediate) include dolichol and ubiquinone

Question 14

Packing of unsaturated fats

Answer 14

• cis double bonds bend the fatty acid chain, reducing the efficiency by which they can pack together
• also true for triacylglycerides
• coconut oil: mostly saturated fatty acids; solid at room temp
• olive oil: many monosaturated fatty acids; liquid at room temp
• fish oil: many polyunsaturated fatty acids; liquid at room temp

Question 15

Fatty acids influence the fluidity of membranes

Answer 15

• cell membranes must be fluid at body temp
• membrane fluidity increases with degree of FA chain unsaturation, and decreases with FA chain length
• cholesterol also influences membrane fluidity by smoothing the transition between solid and liquid phospholipid phases
• FA unsaturation has a similar influence on TAG properties

Question 16

Membrane proteins

Answer 16

• classified based on the nature of their interactions with the lipid bilayer
• integral proteins: associate via non-polar interaction and require detergents to extract
• peripheral proteins are associated with the membrane surface via electrostatic contacts
• many integral proteins can span the bilayer as a-helices or b-barrels

Question 17

Sequence-based prediction of a-helical membrane proteins

Answer 17

-a-helical transmembrane domains can often be recognized as stretches of 20 non-polar residues

Question 18

Anchoring of membrane proteins

Answer 18

• proteins may also be attached tightly to the bilayer with lipid anchors
• cytoskeletal proteins restrict lateral motion of proteins in vivo

Question 19

Lipid microdomains (rafts)

Answer 19

• membrane microdomains are relatively transient lateral regions within membrane bilayesr that have distinct lipid/protein compositions and functions
• tend to be thicker, less fluid, and are enriched in cholesterol, sphingolipids and fatty acylated proteins