Question | Answer |
18C amino alcohol | sphingosine |
amide linkages of fatty acids to the nitrogen of sphingosine | ceramides |
represent a phosphorus containing subclass of sphingolipids | sphingomyelins |
ceramides with one or more sugars beta-glycosidic linkages at the 1-hydroxyl group | glycosphingolipids |
glycosphingolipids with ONE sugar | cerebrosides |
glycosphinglipids with 2 or more sugars | globosides |
ceramides with 3 or more sugars, one of which is sialic acid | gangliosides |
gangliosides = ceramides with _#_ or more sugars, one of which is ______ | 3; sialic acid |
esters of long chain alcohols with long chain fatty acids | waxes |
highly insoluble lipid found coating animal skin and fur, in leaves of many plants and bird feathers | waxes |
lipid with ether linkage instead of acyl group at C-1 position of glycerol | ether glycerophospholipids |
ether glycerophospholipids with unsaturated alkyl chain (C-2) | plasmalogens |
terpenes are based on ____ structure | isoprene (5C) |
all sterols (incl. cholesterol) are ____-based molecules | terpene |
many _____ are recognized by their characteristic flavors or odors (ex. limonene, citronellal, pinene, menthol) | monoterpenes |
C20 terpenes; include retinal, phytol, and gibberellins | diterpenes |
lanosterol (constituent of wood fat) is example of ____ (terpene) | triterpene |
tetraterpene; carotenoid found in ripe fruit esp. tomatoes | lycopene |
1. initiation point for synthesis of carbohydrate polymers in animals = ____
2. analogous alcohol of (1) in bacterial systems that consists of 11 ISOPRENE units | 1. dolichol phosphate
2. undecaprenol (AKA bactoprenol) |
delivers sugars from cytoplasm for the synthesis o cell wall components such as peptidoglycans, lipopolysaccharides, and glycoproteins | undecaprenyl phosphate (isoprene) |
____ compounds serve as side chains of Vit. K, the ubiquinones, plastoquinones, and tocopherols (Vit. E) | polyprenyl compounds (isoprene) |
functions as both a hormone and visual pigment of the vertebrate eye | vitamin A |
vitamin A derivative which regulates gene expression in the development of epithelial tissues; isoprene
(hormone fxn of Vit A) | retinoic acid |
vitamin A derivative, pigment that initiates the response of rod and cone cells of the retina to light; isoprene
(visual pigment fxn of vit A) | retinal |
What activates inactive retinal (Vitamin A1 derivative) to change to functional retinal (pigment for vision)? | VISIBLE LIGHT makes 11C-12C double bond TRANS from cis |
_____ is not itself biologically active, but is converted by enzymes in the liver and kidney to 1,25-dihydroxycholechalciferol, a hormone that regulates CALCIUM UPTAKE in the intestine and CALCIUM LEVELS in kidney and bone | Vitamin D3 |
deficiency of vitamin D leads to _____ | defective bone formation |
collective name for a group of closely related lipids called TOCOPHEROLS | Vitamin E |
hydrophobic, associate with the membranes and lipoproteins in blood, collectively called Vitamin E
--Biological antioxidants | Vitamin E |
Why are tocopherols (Vit E) considered biological antioxidants? | the aromatic ring reacts with and destroys the most reactive forms of oxygen radicals and other free radicals, protecting unsaturated FA from oxidation and preventing oxidative damage to membrane lipids |
principle symptom of vitamin E deficiency? | fragile erythrocytes |
The aromatic ring of _____ undergoes a cycle of oxidation and reduction during the formation of active PROTHROMBIN, a blood plasma proteolytic protein essential in blood clot formation | Vitamin K |
activated ____ splits peptide bonds in the blood protein fibrinogen to convert it to fibrin, the insoluble fibrous protein that holds blood clots together | prothrombin (formed from Vit K) |
Vit K deficiency leads to ______ | slows blood clotting (can be fatal) |
Coumadin (widely prescribed anticoagulant) and Warfarin (component of rodent poisons) act as _____ | antagonists of Vitamin K in body (so slows/prevents blood clotting) |
stimulates the carboxylation of proteins participating in blood clotting cascade = ___1___
Carboxylation of these coagulation factors is catalyzed by a carboxylase that requires the ___2___ form of (1), molecular oxygen, and CO2 | 1. Vitamin K
2. reduced |
Enzyme targeted by Coumadin and Warfarin? | Vitamin K epoxide reductase (blood clotting requires redox reactions of Vitamin K) |
Steroids: based on a core structure consisting of __ 6-membered rings and __ 5-membered rings, all fused together | 3 6-membered
1 5-membered |
most common steroid in animals and precursor for all other steroids in mammals | cholesterol |
serve many functions in animals incl. salt balance, metabolic function, and sexual function | steroid hormones |
BILE ACIDS = polar derivatives of ____
BILE SALTS = synthesized from ____ and stored in the ____ | cholesterol
synthesized from CHOLESTEROL in LIVER
stored in GALL BLADDER |
Bile = ? | mixture of bile acids, cholesterol, and pigments from breakdown of RBC |
Bile is secreted into the ____ after a fatty meal
Function of bile? | small intestine
acts as a DETERGENT emulsifying dietary fats to make them more readily accessible to DIGESTIVE LIPASES |
taurocholic acid = example of ____ | bile acid |
impt precursor for many steroid hormones (incl. testosterone, estradiol, cortisol, aldosterone, prednisolone, prednisone) | cholesterol |
formation of an amide linkage between a FA and a sphingosine produces a _____ | ceramide |
constitute the boundaries of cells and intracellular organelles; also provide a surface where many impt biological reactions such as electron transport, oxidative phosphorylation, electrical activity, and signaling occur | membranes |
T/F Lipids form ordered structures spontaneously in water. | true |
Monomer lipids? | Very few lipids exist as monomers |
How do micelles react to nonpolar solvents? | reverse, tails go to outside |
two ways lipid bilayers can form? | 1. unilamellar vesicles (liposomes)
2. multilamellar vesicles |
Components of the Fluid Mosaic Model? | 1. phospholipid bilayer = fluid matrix
2. bilayer = two-dimensional solvent
3. Lipids and proteins can undergo rotational and lateral mov't
4. 2 classes of proteins: peripheral (extrinsic) and integral (intrinsic) |
Where does cholesterol occur in membrane? | integrated |
how has lipid diffusion (migration of lipids and proteins in the bilayer) been shown? | NMR and EPR as well as fluorescence measurements |
How are proteins and lipids arranged in membrane? | LATERAL ASYMMETRY of both lipids and proteins - they can cluster in the plane of the membrane and are not uniformly distributed |
What might induce phase separations of components of membrane (form liposomes)? | divalent cations such as Ca2+ |
membrane protein known to SELF-ASSOCIATE or form clusters in nonrandom formations) | Bacteriorhodopsin forms clusters known a PURPLE PATCHES in membranes of Halobacterium halobium |
Transverse Asymmetry of proteins: Bark Bretscher showed that the ___ of glycophorin is extracellular wherease ____ is intracellular | N-terminus = extracellular
C-terminus = intracellular |
Transverse Asymmetry of lipids: in most cell membranes, the composition of the ____ is different from the _____ | Outer monolayer is different from the inner monolayer |
proteins that move lipids from one monolayer to the other
Where do these proteins get energy? | Flippase Proteins
Some are passive and do not require an energy source
Most require energy hydrolysis of ATP (ex. in erythrocytes) |
What type of flippase can generate membrane asymmetries? | Active Flippase (uses ATP hydrolysis) |
Phase transitions in membranes?
**only pure lipid systems give sharp, well-defined transition temperatures | Below a certain transition temp - membrane lipids are rigid and tightly packed
Above the transition temp - lipids are more flexible and mobile
**The transition temperature is characteristic of the lipids in the membrane |
What happens to membrane as it is WARMED? | Surface area increases as thickness decreases. Mobility of the lipid chains INC dramatically (goes through phase transition) |
proteins which are NOT strongly bound to membrane, can be dissociated from the membrane by treatment with salt solutions or changes in pH | Peripheral proteins |
proteins that are imbedded in bilayer; can removed only by agents capable of breaking up the hydrophobic interactions within the lipid bilayer itself
--often transmembrane but not necessarily
--Ex. glycophorin, bacteriorhodopsin | integral membrane proteins |
A single transmembrane segment with globular domains on either end
transmembrane segment is ____ (shape) and consists of __#__ hydrophobic amino acids | Glycophorin
alpha helical; 19 AA |
Extracellular portion of glycophorin (transmembrane protein) contains ____ which constitute ______ determinants | oligosaccharides; ABO and MN blood group determinants |
spans the membrane of the human erythrocyte via a single alpha-helical transmembrane segment
C-terminus faces _____
N-terminus points to _____
What attaches to the N-terminus? | Glycophorin A
C-terminus faces cytosol of erythrocyte
N-terminus faces extracellular side
Carbohydrates |
a 7-transmembrane-segment (7-TMS) protein
--found in purple patches of Halobacterium halobium
--consists of 7 transmembrane helical segments with short loops that interconnect the helices
--light driven proton pump | Bacteriorhodopsin |
Bacteriorhodopsin = a ____ protein, ___-driven proton pump found in _____ | 7-TMS protein
LIGHT driven proton pump
Purple patches of Halobacterium halobium |
Where are porins found? | in both Gram - bacteria and in mitochondrial outer membrane |
pore-forming proteins (30-50 kD)
--general or specific (exclusion limits 600-6000)
--most arrange in membrane as trimmers
--high homology between various proteins
--make beta barrels | Porins |
Most porins arrange in membrane as ____ | trimers |
PORIN from Rhodobacter capsulatus has _____ that transverses the membrane to form the pore | 16-stranded beta barrel |
a relatively new class of membrane proteins; 4 types have been found:
-amide-liked myristoyl anchors
-thioester-linked fatty acyl anchors
-thioether-linked prenyl anchors
-glycosyl phosphatidylinositol anchors | Lipid-Anchored Membrane Proteins |
Type of lipid-anchored membrane protein?
--always myristic acid
--always N-terminal
--always a Gly residue that links | Amide-linked myristoyl anchors |
The following proteins are examples of ____:
cAMP-dependent protein kinase
pp60^sro
tyrosine kinase
calcineurin B
alpha subunits of G proteins
gag protein of HIV-1 | amide-linked myristoyl anchors |
amide-linked myristoyl anchors:
1. always ____ acid
2. always __-terminal
3. always a ___ residue that links | 1. myristic acid
2. N-terminal
3. Gly |
N-myristoylation always occurs at _____ | N-terminal glycine residue |
Anchor with broader specificity for lipids - myristat, Palmitate, stearate, oleate all found | Thioester-linked acyl anchors |
The following are examples of _____:
G-coupled protein receptors
Surface glycoproteins of some viruses
Transferrin receptor triggers and signals | Thioester-liked acyl anchors |
S-pamitoylation always occurs at the ____ residues of polypeptide chain. | cysteine |
G-protein coupled receptors, with seven transmembrane segments, may contain one (or two) palmitoyl anchors in thioester linkage to _____ residues in the __-terminal segment of the protein | cysteine; C-terminal |
Anchors: Prenylation refers to linking of "isoprene" based groups
--always Cys of CAAX (C=Cys, A=Aliphatic, X=any residue)
--isoprene groups include farnesyl (15C, 3 double bond) and gernaylgeranyl (20C, 4 double bonds) gropus | Thioether-linked prenyl anchors |
The following are examples of _____:
yeast mating factors
p21^ras
nuclear lamins | Thioether-linked prenyl anchors |
Proteins containing the C-Terminal sequence CAAX can undergo ____ reactions that place ____ at the CYSTEINE side chain | prenylation
thioether linked farnesyl or geranylgeranyl groups |
_____ is accompanied by the removal of the AAX peptide and the methylation of the carboxyl group of the cysteine residue, which has become the _____ residue | Prenylation; C-terminal |
____ is a small GTP-binding protein involved in cell signaling pathways that regulate cell growth and division
--mutations in this are involved in 1/3 of all human cancers
--it is dependent on prenylation and the proteolysis of the -AAX motif | RAS |
Because the signaling activity of RAS is dependent on __1__, the reaction itself, as well as the proteolysis of the __2__ motif, and the methylation of the __3__, have been considered targets for development of NEW CHEMOTHERAPY strategies | 1) prenylation
2) -AAX motif (from the C-terminal sequence CAAX, the -AAX is removed)
3) prenylated Cys residue (what is left at the end of the C-terminal after proteolysis) |
Anchors that are more elaborate than the others
--always attached to C-terminal residue
--Ethanolamine link to an oligosaccharide linked in turn to inositol of PI | Glycosyl Phosphatidyllinositol Anchors |
GPI anchors are always attached to a ____ residue | C-terminal |
The following are examples of _____:
surface antigens
adhesion molecules
cell surface hydrolases | Glycosyl Phosphatidylinositol anchors |
Core of Glycosyl phosphatidylinositol (GPI) = _______
Additional modifications may include FA at the ___ and ___ -OH groups | 3 mannose residues and a glucosamine (elaborate lipid-anchoring group)
inositol and glycerol |
When transported species simply move down its concentration gradient (from high cxn to low cxn) | passive diffusion |
What does a high permeability coefficient signify? | passive diffusion is not the whole story |
Passive diffusion of an UNCHARGED species depends on: | only the concentrations on the two sides of the membrane |
Passive diffusion of a CHARGED species depends on: | 1. CONCENTRATION of particle Z
2. CHARGE of particle Z
3. ELECTRICAL DIFFERENCE across the membrane (delta psi) |
How does facilitated diffusion occur? | solutes only move in the thermodynamically favored direction but proteins may facilitate transport increasing the rates of transport |
2 impt distinguishing features of facilitated diffusion? | 1. Solute only flows in favored direction
2. Transport displays saturation kinetics |
How does energy input drive active transport processes? | Energy source and transport machinery are coupled so that solutes can flow against thermodynamic potential.
Energy source may be ATP, light or a concentration gradient. |
SODIUM PUMP: large protein (120kD and 35kD)
1) maintains intracellular ___ low and ___ high
2) Crucial for all organs but esp. ___ and ___
3) ATP hydrolysis drives ___ out and ___ in | 1) Na low & K high
2) neural tissue and brain
3) Na+ out & K+ in |
SODIUM PUMP:
1) Alpha subunit has 10 transmembrane ____ with a large cytoplasmic domain
2) ATP hydrolysis occurs via _____
3) _____ inhibit by binding to outside | 1) helices
2) E-P intermediate
3) cardiac glycosides |
For sodium pump what moves in and out per ATP? | 3 Na+ out and 2 K+ in |
osteoclasts vs osteoblasts? | **Bone material undergoes ongoing remodeling.
OsteoCLASTS tear down bone tissue
OSTEOBLASTS build it back up |
How do osteoclasts function? | by secreting acid into the space between the osteoclast membrane and the bone surface. Acid dissolves the Ca-phosphate matrix of the bone.
**It is all driven by an ATP proton pump in the membrane |
Proton pumps cluster on the ruffled border of ____ and function to pump protons into the space between the cell membrane and the bone surface.
____ ____ concentration in this space dissolves the mineral matrix of the bone | osteoclast cells
High proton concentration |
a member of a "superfamily" of genes/proteins that appear to have arisen as a "tandem repeat"
--defeats efforts of chemotherapy
--recognizes a broad variety of molecules and transports them out of the cell using the hydrolytic energy of ATP | MDR ATPase (AKA the P-glycoprotein) - an organic molecule pump |
MDR ATPase: this multidrug transporter is postulated to have _#_ transmembrane alpha-helices and _#_ ATP binding sites
**Some of cytotoxic drugs are transported by MDR ATPase (Colchicine, Vinblastine, Adriamycin, and Vincristine) | 12 transmembrane alpha-helices (HUGE!)
2 ATP binding sites |
How is amino acid and sugar transport driven by ion gradients? | SECONDARY ACTIVE TRANSPORT
Does not use ATP directly, but uses the gradient of other compounds ---> Symport and Antiport |
Symport vs antiport (2* active transport) | Symport = ion and the AA or sugar are transported in the same direction across the membrane
Antiport = ion and transported species move in opposite directions |