Flashcards in chapter 12 Deck (109):
what are biological membranes?
barriers that define inside and outside of a cell
what confers selective permeability of membranes?
sheetlike structures, only 2 molecules thick, that form closed boundaries between different compartments.
6-10 nm. contain lipids and proteins, may also contain carbohydrates linked to lipids and protein
what are membrane lipids like?
small molecules that have both hydrophilic and hydrophobic moieties. these spontaneously form closed bimolecular sheets in aqueus media.
what are protein functions in membranes?
pumps, channels, receptors, energy transducers, and enzymes.
what does it mean by membranes are noncovalent assemblies?
the consituient protein and lipid molecules are held teogether by many noncovalent interactions which are cooperative
what does it mean by membranes are asymmetric.
2 faces of biological membranes always differ from each other
what does it mean by membranes are fluid structures?
lipid molecules diffuse rapidly in the plane of the membrane as do proteins, unless they are ancored by specific interactions.
what does it mean that membranes can be regarded as 2-dimentional solutions of oriented proteins and lipids?
lipid molecules do not readily rotate across the membrane
what does it mean by most cell membranes are electrically polarized
inside is negative (about -60 mV) and membrane potential plays a key role in transport, energy conversion, and excitability
what are fatty acids?
hydrocarbon chains of various lengths and degrees of unsaturation that terminate with carboxylic acid groups
16 carbon saturated
18 carbon with single cis double bond
how do you name fatty acids?
systematic name for fatty acid is derived from the parent hydrocarbon name and substituting oic for e. (octadecanoic acid -->octadecane) if it had 1 double bond it would be called octadecenoic acid. with 2-3 double bonds (octadecadienoic acid/ octacecatrienoic acid)
how would you denote an 18 carbon fatty acid with 0 or 2 double bonds?
18:0 or 18:2
how are fatty acids numbered and what is the alpha, beta, and omega carbon atom?
numbered from carboxyl terminous, carbons 2 and 3 are alpha and beta, methyl carbon atom at the distal end of the cina is called the omega-carbon
how are the position of double bonds denoted?
represented by cis /trans then delta signal followed by super script (cis-delta^9) means there is a cis double bond between 9 and 10.
are fatty acids of biological systems usually even numbered
what are the most comon numbered fatty acids?
16 and 18 carbons
are hydrocarbons usually branched or unbranched in animal fatty acids?
unbranched (almost invariably)
what is the configuration of most double bonds?
cis. (trans fats are bad!)
what is a polyunsaturated fatty acid?
double bonds in polyunsaturated fatty acids are separated by at least one methylene group?
why are fatty acids referred to as their carboxylate form?
they are ionized at physiological pH
what are physical properties of fatty acids dependent on?
dependent on chain length and dgree of saturation. unsaturated fatty acids have lower melting points than saturated fatty acids of the same length. melting points of polyunsaturated fatty acids are even lower. shorter chains have lower melting temperatures than longer chains.
what enhances fluidity of a membrane?
short chain length and unsaturation
what are 4 biological roles of lipids?
1. fuel molecules
2. highly concentrated energy stores
3. signal molecules
4. components of membranes
what are the 3 membrane lipids?
phospholipids, glycolipids, cholesterol
what are the 4 components of phospholipids?
1. fatty acids
2. platform to which the fatty acids are attached
4. alcohol attached to phosphate
hydrophilic properites enable interaction with environment
what is the platform on which phospholipids are built?
glycerol, 3-carbon acohol, or spingosine (more complex alcohol)
what is a phosphoglyceride?
phospholipid derived from glycerol. consists of a glycerol backbone to which 2 fatty acid chains and a phosphorylated alcohol are attached
what is the simplest phosphoglyceride and what is it used for?
phosphatidate (diacylglycerol 3-phosphate). key intermediate in the biosyntehsis of the other phosphoglycerides
how are major phosphoglycerides derived from phosphatidate?
formation of ester bond between the phosphate group of phosphatidate and the hydroxyl group of one of the several alcohols.
what is sphingomyelin?
phospholipid found in membranes that is not derived from glycerol, backbone is sphingosine, amino group of sphingosine is linked to a fatty acid by an amide bond. primary hydroxyl group is esterified to phosphoryl choline
what is sphingosine?
amino alcohol that contains a long, unsaturated hydrocarbon chain.
what are glycolipids
sugar containing lipids
what are glycolipids derived from?
derived from sphingosine
the amino group of the glycolipid sphingosine backbone is ________by a fatty acid
how do glycolipids differ from sphingomyelin
1. the identity of the unit
that is linked to the primary hydroxyl group of the sphingosine
2. In glycolipids, one or more sugars (rather than phosphoryl choline)
are attached to this group
what is the simplest cerebroside
the simplest glycolipid. contains a singal sugar residue. (glucose or galactose)
what are gangliosides
more complex glycolipids that contain a branched chain of as man yas seven sugar residues
why are glycolipids considered to be oriented asymmetrically?
completely asymmetric because the sugar residues are always on the extracellular side of the membrane
lipid with a structure quite different from phospholipids. it is a steroid built from 4 linked hydrocarbon rings. a hydrocarbon tail is linked to the steroid at one end and a hydroxyl group is attached at the other end.
how is cholesterol oriented in membranes?
molecule is oriented parallel to the fatty acid chains of the phospholipids. hydroxyl group interacts with nearby phospholipid head groups
what is unique baout archaeal membranes. why do they have unique properties?
live under extreme condtions such as high temperature, low pH or high salt concentration.
1. nonpolar chains joined to a glycerol backbone by ether rather than ester linkages (ether linkage more resistant to hydrolysis)
2. alkyl chains are branched rather than linear; branched, saturated hydrocarbons are more resistant to oxidation
3. sterochemistry of the central clycerol is inverted
what does amphipathic mean
contains both a hydrophilic and hydrophobic moiety
what properties enable phospholipids to form membranes?
amphipathic nature, polar head groups favor contact with water, hydrocarbon tails interact with each other. to satisfy these constraints, lipids can form micelles and bilayers
what is a micelle
globular structure in which polar head groups are surrounded by water and hydrocarbon tails are sequestered inside
what are 2 opposing sheets of a bilayer called
why do phospholipids usually form bimolecular sheets instead of micelle
2 fatty acid chains of a phospholipid or glycolipid are too bulky to fit into the interior of a micelle.
what do salts of fatty acids form?
sodium palmitate, only contains one chain, readily forms micelles
how big are micelles vs biomolecular sheets?
micelles are usually less than 20nm, bimolecular sheet can have macroscopic dimensions such as a mm
how is lipid bilayer formed. what are the major driving force of formation?
self assembly. rapid and spontaneous process in water.hydrophic interactions major driving force for the formation of lipid bilayer
what forces are at work during lipid bilayer formation
water molecules are released from the hydrocarbon tails of membrane lipids as tails become sequestered in nonpolar interior, van der waals attractive forces between hydrocarbon tails favor close packing of tails, electrostatic and hydrogen bonding attractions between polar head group and water molecules
what is a cooperative structure
structure, such as lipid bilayer held together by many reinforcing, noncovalent interactions
more realistic view of fluid bilayer shows?
more irregular structures of the fatty acid chains
what are the 3 significant biological consequences of hydrophobic interactions in lipd bilayers?
1.! Lipid bilayers have an inherent tendency to be extensive
2.! Lipid bilayers will tend to close on themselves so that there are no
edges with exposed hydrocarbon chains ! form compartments
3.! Lipid bilayers are self-sealing because a hole in a bilayer is
aka liposomes, aqueus compartments that are enclosed by a lipid bilayer. can be made in lab and used to study membrane permeability or to deliver chemicals to cells
how are lipid vesicles/liposomes formed?
suspending a suitable lipid such as phosphatidyl choline, in an aqueus medium and then agitating by high frequency sound waves. you get dispersion of closed vesicles (about uniform in size 50nm diameter, spherical in shape, with ions or molecules trapped in the aq compartment)
how many molecules will a 50nm diameter vescile store?
50nm diameter formed in .1 M glycine solution will trap about 2000 molecules of glycine in each compartment
how are glycine containing vesicles separated from surrounding solution?
how is permeability of the bilayer membrane to glycine measured?
measure rate of efflux of glycine from inner comparment of vescicle to the ambient solution
how to make protein liposome complexes?
specific membrane protines can be solubilized in the presence of detergents and then added to the phospholipids from which liposomes will be formed
clinical uses for liposomes
-lipsomes containing drugs or dna for gene therapy can be injected into patients. lipsomes fuse with plasma membrane and relsease contents inside target cell. often lessens toxicity, and less of the drug is distributed to normal tissues because long circulating liposomes concentrate in regions of increased blood circulation such as solid tumors and sites of inflammation
how to study electrical conduction properties of macroscopic bilayer?
make a synthetic membrane across a 1 mm hole in a partition between 2 aqueous compartments. insert electrodes into each aqueous compartment to study electrical conduction.
how is permeability to ions determined
by measuring current across the membrane as a function of the applied voltage (in a sythetic membrane box thingy)
permeability coefficients of small molecules are correlated with solubility in a nonpolar solvent relative to their solubility in water. this suggests...?
when traveling through the membrane a small molecule first sheds its solvation shell of water, becomes disoolved in the hydrocarbon core of the membrane, finally diffuses through thi s core to the otherside of membrane to be solvated by water
what function does having a low protein content provide protein myelin
what is the protein content of exterior cell membranes
about 50 percent.
protein content of energy-transduction membranes
75% for eunergy transdction membranes such as mitochindrial and chloroplasts
how are proteins dissociated from membranes
through chemical treatment (some require mild treatments such as high ionic strength solution (1M nacl) others need a detergent or organic solvent due to being bound very tightly
peripheral membrane proteins
bound to membranes primarily by electrostatic and hydrogen bond interactions with the head groups of lipids or with interaction with integral membrane proteins
integral membrane proteins
interact extensively with the hydrocarbon chains of membrane lipids
what is bacteriorhodopsin
archaela protein that acts in energy transduction by using light energy to transport protons from inside the cell to the outside of the cell. proton gradient generated used to form ATP
built of alpha helices, 7 closely packed alpha helices arranged almost perpedicularly to the plane of the membrane
most common structural motif in membrane proteins?
membrane spanning alpha helicies
what is a porin
a protein from the outer membranes of bacteria, represent a class of membranes built from beta strands and contain no alpha helices. porins form holes or channels in the membranes. used to control diffusion of small polar metabolites like sugar, ions, and amino acids
structure of porin
each strand is hydrogen bonded to its neighbor in an antiparallel parangement forming a singal beta sheet--beta sheet curls up to form a hollow cylinder that functions as the active unit. outside surface is nonpolar, inside is hydrophilic and filled with water
how does a porin have polar and nonpolar surfaces?
This arrangement of nonpolar and polar surfaces is accomplished by
the alternation of hydrophobic and hydrophilic amino acids along
each beta strand
the space between the inner cytoplasm membrane and external outer membrane of gram-negative bacteria
what does the periplasm contain?
contains a loose network of murein peptidoglycan chains, as well as a gel containing hydrolytic and degradative enzymes
what is prostaglandin H2 syntehase -1
produces protaglandin H2, which promotes inflammation and modulates gastic acid secretion
structure of h2 synthease-1?
homodimer with complicated structure of alpha helices.
where do you find h2 synthase-1?
not embedded in the membrane, lies along the outer surface of the membrane firmly bound by a set of alpha helices with hydrophobic surfaces that extend from the bottom of the protein to the membrane. ingetral membrane protein
what does it catalyze and what are the 2 steps of prostaglandin H2 synthase-1
catalyzes the conversion of arachidonic acid ito prostoglandin H2:
1. cyclooxygenase reaction (inhibited by asprin)
2. peroxidase reaction
why is the localization of prostaglandin H2 synthase-1 in the membrane crucial to function
the substrate for this enzyme arachidonic acid is a hydrophobic molecule generated by hydrolysis of membrane lipids. arachidonic acid reaches actie site from the membrane witout entering aqueous environment by traveling through a hydrophobic channel in protein
how does aspirin and ibuprofen block prostaglandin h2 synthase 1
block the channel and prevent prostaglandin syntehsis by inhibiting the cyclooxygenase activity of the synthase. aspirin acts through the transfer of an acetyl group from aspirin to a serine residue that lies along the path to the active site
what are 3 examples of soluble proteins associated with the membrane, and how do they associate with the membrane?
mediated by hydrophobic groups attached to the proteins
1. palmitoyl group attached to a specific cysteine residue by a thioester bond
2. a farnesyl group attached to a cysteine residue at the carboxyl terminus
3. a glycolipid structure termed a glycosyl phosphatidyl inositol (GPI) anchor attached to the carboxyl terminus
residues on alpha helices that span the hydrophobic part of the membrane are:
nonpolar and almost none are charged.
how can you identify putative membrane spanning regions from the sequence data alone
look for alpha helices that are nonpolar/not charged/look at alpha helicies and ask whether it is ost stable in hydrocarbon solvent or in water
how do you predict transmembrane helicies
30 angstroms wide, (can be traversed by a helix consisting of 20 residues) estimating the free energy change when a helical segment (residue 1-20) is transferred from interior of membrane to water. make same calculation for window of residues (i.e. 2-21, 3-22) until reaching the end of the sequence
what is a hydropathy plot
free-energy change for each window is plotted against the first amino acid. a peak of +84 kJ/mol in a hydrophathy plot based on a window of 20 residues indicates that a polypeptide segment could be a membrane spanning alpha helix
issues withy hydropathy plot
peaks do not prove segment is a transmembrane helix. soluble proteins may have highly nonpolar regions. some membrane proteins contain transmembrane structural features that cannot be detected (beta strands)
what is lateral diffusion
lipids and many membrane proteins constantly in lateral motion. proteins vary in lateral mobility, some are very mobile like lipids, others immobile
how long does it take for a lipid molecule to travel from one end of a bacterium to the other
what is the viscosity of a membrane?
100 times water
the fluid mosaic model
proposes that membranes are 2 dimentional solutions of oriented lipids and gobular proteins.
what is the dual role of the lipid bilayer
solvent for integral membrane proteins and permeability barrier
how long does it take for rotation of a lipd from one face of a membrane to the other
very slow hours
why are free energy barriers for flipflopping even larger for protein molecules than for lipids?
proteins have more extensive polar regions (protein flip flop never actually observed before
how does temperature affect membrane fluidity
transition from rigid to fluid occurs abruptly as temp is raised above melting temp
what does transition temperature depend on?
lenght of fatty acyl chains and their degree of unsaturation. presenece of saturated acyl residues favors the rigid state because straight hydrocarbon chains interact very favorably with each other. cis double bond produces a bend in the hydrocarbon chain which interferes with packing and favors fluid state
how do bacteria regulate fluidity of their membranes
by varying number of double bonds and the length of their fatty acyl chains
how do animals regulate membrane fluidity
cholesterol inserts into bilayers with long axis perpendicular to plane of membrane.different shape of cholesterol compared to phospholipids disrupts regular interactions between fatty acyl chains and increases fluidty
describe asymmetrical composition of red blod cell membrane
sphingomyelin and phosphatidyl choline are preferentially located in the outer leaflet, while phosphatidyl ethanolamine and phosphatidyl serine are located mainly in the inner leaflet
na+ k+ pump assymetrical so that
it pumps na+ out of the cell and k+ into the cell. atp must be on the inside of cell to drive pump
organelles that play a major role in the oxidation of fatty acids for energy conversion (defined by a single membrane
organelles in which atp is synthesized - surrounded by 2 membranes
surrpounded by 2 membranes