function of lipids
building blocks of membranes
energy storage
hormones
mediators of signal transduction
fatty acids
have carboxylic acids with long-chain hydrocarbon side group
can be saturated
can be unsaturated - dbl bonds are almost always in cis configuration with rigid 30* bend in hydrocarbon chain
nomenclature
carboxylic acid is given highest priority
18:0 = 18 is # of carbons, 0 is # of dbl bonds
structure of fatty acids
most have even # of carbon atoms
hydrocarbon chain is almost always unbranched
most c-c bonds are single but may have 1, 2, or more dbl bonds
dbl bonds are usually cis
for monounsaturated fatty acids, dbl bond is usually btwn C9 and C10
if ore than 1 C-C
triacylglycerols
triesters of glycerol and fatty acids
can be fats (solid at room temp) or oils (liquid at room temp, lower MP)
energy storage and thermal insulation
function as metabolic energy reservoirs
trans fats
these are liquid cis-fats that have been hydrolyzed imperfectly to a solid
isomerization of cis dbl bond occurs
body has hard time metabolizing these --> clogs arteries and accumulates in circulatory system
adipocytes
fat cells
really important endocrine organs and function in storage too
synthesis and storage of fats (triacylglycerols)
secretion of protein hormones related to glucose homeostasis (adiponectin, leptin, resistin, etc)
glycerophospholipids
amphiphilic
major components of biological membranes
signal transduction
head groups are derived from polar alcohols
has one straight chain, one kinked chain for two tails
phospholipases
hydolyze phospholipids
sphingolipids
backbone is sphingosine
found in myelin sheath on nerve cell axons
glycolipids
abundant in brain and nerve membranes
cell-cell recognition
functions of steroids
components of membranes (cholesterol)
bile acids help digesstion of fatty acids (cholic acid and glycocholic acid)
hormones (estrogens, androgens, progesterones, glucocorticoids, mineralocorticoids)
cholesterol
membrane component
precursor of steroid hormones
precursor of bile salts
bile acids
more hydrophilic groups
phytosterols
plant steroids
fungi also have different steroids... important in development of anti-fungals
vitamin D
naturally synthesized
1st rxn is driven by UV radiation/free radical rxn
vitamin D increases absorption into of Ca2+ and increase Ca2+ in blood so it can be deposited in bone/teeth
without dietary calcium, Ca2+ will be released from bone
fat soluble vitamins
must have optimum amounts in body bc they can accumulate in the body
Coenzyme Q, Retinol A, Retinal, a-tocopherol (found in cosmetics)
coenzyme Q
different forms based on oxidation
mainly found in membrane of mitochondria
heart muscle requires a lot of this... must take if you are on cholesterol lowering drugs bc it is not being produced
isoprenoids
aka terpenoids
plants make a lot of this type of lipids
has branched chains
eicosanoids
eicos" means 20
derived from arachidonic acid (C20)
prostaglandins, thromboxanes, and leukotrienes - all cytokines
regulate pain, fever, blood pressure, blood coagulation, and reproduction
produced and act locally (paracrine signaling) at low concentrati
arachidonate pathway
COX cyclizes the arachidonic acid to create pain causing molecules
COX (enzyme) is important in inflammation/pain control at injury site
COX-1
constitutive, expressed in most tissues
cell maintenance and housekeeping
synthesis of prostaglandins responsible for protection of the stomach lining
COX-2
induced by inflammatory stimuli such as injury or disease (external signals)
synthesis of prostaglandins responsible for pain and inflammation
NSAIDs
non-steroidal anti-inflammatory drugs
can be inhibitors of cox-1 and cox-2 - OTC
selective inhibitor of cox-2 - prescription
too much of these is BAD... can cause stomach bleeding
micelles
single-tailed lipids tend to form these in water
single tail is more cone shaped
bilayers
lipids with two hydrocarbon tails tend to form these
both sphingolipids and phospholipids
two hydrocarbon chain tail is more box shaped
liposome
closed membrane, self-sealing vesicle that is bounded by a single bilayer
membrane is fluid
several hundred A in diameter
very stable
can be purified by dialysis, gel filtration, centrifugation
models for biological membranes, drug delivery
made by dissol
two-dimensional fluids
lipid bilayers are ________ _________ (dynamic!)
transverse diffusion
flip-flop
RARE/very slow
hard to do vertical flip bc polar head must go through hydrophobic core
lateral diffusion
rapid
highly mobile in plane of bilayer
FRAP
fluorescence recovery after photobleaching
proves lateral movment
bleach a fluorophore so there is no fluorescence in a region of a bilayer
after a while it recovers and unbleached lipids move into the bleached region
structure of lipid bilayer
about 60 A thick
head groups are each ~15 A thick
hydrophobic core is ~30 A thick
high viscosity in head groups
hydrocarbon tails bend and interdigitate
water penetrates to the edge between head groups and hydrophobic cores
phase transition
above transition temp, have highly mobile bilayer (liquid crystal)
at transition temp, bilayer becomes gel-like solid and loses fluidity which is BAD
longer the chain the chain length and they higher the degree of saturation = higher transition temperatur
broadens
cholesterol _______ melting temp for phase transition of bilayers
cholesterol can both stiffen the membrane above melting temp and inhibit regularity in structure formation below melting temp
without cholesterol, bilayer has sharp Tm
once bilayer is "gel
integral membrane proteins
aka intrinsic proteins
permanently embedded in membrane
tightly bound by hydrophobic interaction btwn core/tail residues
only isolable by treatment with agents that disrupt membranes like organic solvents, detergents, or chaotropic agents
tend to aggregat
peripheral protein
weak interaction with head groups, can dissociate
usually found on inside, but can be on outside too
bound to membrane head groups and/or integral proteins by electrostatic and hydrogen interactions
isolable by mild procedure without membrane disruption (
lipid-linked protein
covalent linkage between proteins and lipids
anchor proteins to membranes
mediate protein-protein interactions
asymmetrically oriented amphiphiles
monontropic proteins
transmembrane proteins
usually N-terminus on outside & C-terminus on inside
can be embedded in membrane, but only found in 1 side of membrane too
transmembrane domains
____ ________ contain a helices or B barrels
prenylation
type of lipid-linked protein
isoprenoid groups
hydrophobic prenyl group can act to anchor its attached protein to membrane
ex. farnesylation (C15), geranylgeranylation (C20)
fatty acylation
fatty acid attached to protein, type of lipid-linked protein
ex. myristic acid (C14), palmitic acid (C16)
GPI-linked proteins
glycosylphosphatidylinositol
anchor proteins to exterior surface of plasma membrane
contain a phospholipid
fluid mosaic model
membranes are fluid
proteins float freely in a sea of lipids
this model is generally true, but not all parts of a membrane are accessible to all proteins
has been verified by fusion of two different colored cells
freeze fracture
freeze membrane
cut membrane into monolayer using a microtome knife
make metallic replica and analyze with e- microscopy
freeze-etch procedure
external surface of membrane adjacent to cleaved area is revealed by ______ _________ ______ or sublimation of ice
composition
inner and outer leaflet of membrane differs in lipid _________
specific enzymes do the flip-flop if found on either side
ex. phosphatidylserine is never found on outside
lateral organization
non-uniform distribution of lipids and proteins, forming distinct domains in the plasma membranes
-integral protein patches (aggregates that don't move)
-specific interaction of integral proteins with particular lipids
-phase separation by metal ions (e.g
erythrocyte membrane
easy preparation of erythrocyte membrane
-erythrocyte is devoid of organelles (membranous bag of hemoglobin)
-osmotic lysis of erythrocyte and resealing the resultant membrane particles leads to a colorless erythrocyte ghost --> pop and reform
erythrocyte
bioconcave
_____ disk-like shape of erythrocytes is determined by cytoskeleton of proteins
gap junctions
intercellular communication channels
-heart contraction synchronization - main reason heart has synchronized movement
-embryonic development
-nutrient supply of bone and lens cells
makes channel between two cells for nutrients, ions, etc
contain connexon
channel-forming proteins
TOXINS
water soluble monomers oligomerize to form a transmembrane pore (e.g. bacterial channel-forming toxins)
ex. a-hemolysin from staphylococcus aureus
chemically
can ______ label lipids using TNBS
location of lipid synthesis
lipids are fabricated on site... on cytoplasmic face of membrane
experiment proved lipids made on inside of cell
right after synthesis, there is no label...
if you let it incubate, there is label seen
flipases
facilitate transverse diffusions (flip-flops)
doesn't use energy
phospholipid translocases
transport specific phospholipids across a bilayer with ATP hydrolysis
requires energy