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Fun 1 Exam 2 A

Lipids and Membranes

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
Created by: erinlwilliams