Lect 2 Membranes/Transport Flashcards
What are two important roles of physiological membranes
Selective permeability of metabolites
Transport or exchange of materials
Membranes are arranged in a _ bilayer
Assymetric
Define semi-permeable
Allows small molecules and lipid soluble molecules to diffuse through
What are the primary components of membranes
Phospholipids
What does amphipathic mean?
- Hydrophilic/Polar head groups and Hydrophobic/Nonpolar tails
What are the two types of Phospholipids (PL) ?
What are their structures?
Examples of each?
-
Glycerophospholipids
-
Glycerol backbone attached to phosphate head group and 2 FA
- Phosphatidylcholine, Phosphatidylserine, Phosphotidylinositol
-
Glycerol backbone attached to phosphate head group and 2 FA
-
Sphingolipids (SL)
-
Sphingosine backbone attached to LCFA and phosphorylcholine
- Sphingomyelin (most common SL in outer leaflet)
-
Sphingosine backbone attached to LCFA and phosphorylcholine
What are glycolipids?
Where are they found?
Sphingosine backbone with oligosaccharide residues
Outer leaflet
What is cholesterol and where is it located in membrane?
Steroid nucleus with hydroxyl group and hydrocarbon side chain
Embedded in the bilayer
How is phosphatidylserine used as marker for apoptosis?
Healthy Cells: PS found in inner leaflet
Apoptosis: PS displayed on outer leaflet (tag for destruction by phagocytes)
Niemann Pick Disease is caused by deficiency in what enzyme?
Associated Sx?
- Deficiency in Acid Sphingomyelinase (A-SMase)
- Lysosomal enzyme breaking down sphingomyelin
- Hepatosplenomegaly, neurological damage, cherry red spot in eye
Where are integral membrane proteins located?
What are polytopic transmembrane proteins and what do they include?
- Embedded in membrane (stabilized by hydrophobic interactions with lipids)
- Integral membrane proteins span entire lipid bilayer
- Includes: transporters, ion channels, and receptors
What are peripheral proteins?
Proteins loosley bound to membrane through electrostatic interactions with lipds or proteins
What are lipid-anchored proteins?
Tethered to membranes by covalent attachment to a lipid
Glycocalyx is a CHO shell due to the presence of glycolipids and glycosylated proteins, what are its 3 key functions?
Protection
Cell Adhesion
Cell Identification
RBCs have antigens on their surface, which antibodies would be present in plasma for each blood group?
Type O: anti-A and anti-B
Type A: anti-B
Type B: anti-A
Type AB: none
Results of incompatible blood transfusion?
Acute hemolysis
Renal failure
Shock
Rh factors (D antigen) are inherited in autosomal dominant fashion, who produces the D antigen?
Rh+ individuals express antigen, Rh- do not
What is erythroblastosis fetalis?
Incompatibility between mother and fetus blood
If mother is Rh- and fetus is Rh+, mother produces antibodies and crosses placenta to attack the fetus
Risk is higher in subsequent pregnancies
What factors influence membrane fluidity?
- Temperature
- Lipid Composition
- Sat FA decrease fluidity, unsat FA increase fluidity
- Cholesterol
- Increases fluidity if rigid, decreases fluidity if fluid
What is spur cell anemia?
What effect does it have on membranes
Elevated levels of cholesterol in RBC membrane
Decreases fluidity and flexibility –> RBC membranes break/lyse passing through capillaries
Which ions have higher concentrations in/out of cells?
Typical Neuron
How does Passive Transport work?
energy-independent mechanism
Molecules move down concentration gradients
Which molecules use simple diffusion?
Small, non-polar and uncharged polar diffuse freely across membrane
How does facilitated diffusion work?
What are the proteins in involved called?
Uses transmembrane proteins for molecules that are large and charged
Ion channels or transporters
How do ligand gated ion channels work?
Ligands bind to channel and induce conformational change
How do voltage gated ion channels work and where are they found?
What does depolarization mean?
How does Tetrodotoxin work?
Open/close in response to changes in the membrane potential (depolarization) and found in excitable cells (neurons)
Depolarization is incrase in membrane potential due to influx of positively charged ions
Inhibits voltage gated sodium channels from opening
How does active transport work?
Energy dependent mechanism moving molecules against their concentration gradient
What are the two types of primary active transport?
-
P type ATPases - ATP hydrolyzed and protein is phosphorylated
- Na/K-ATPase & Ca-ATPase
- ABC transporters - ATP hydrolyzed, but protein not phosphorylated
Describe secondary active transport mechanism?
What are the three different types of secondary active transporters?
- Unfavorable flow of one species against gradient is coupled to favorable flow down gradient
- SGLT, NCX
- Antiporter, Symporter, Uniporter
Sodium Glucose Transporter 1 (SGLT1) function and location
What type of transporter?
- Unidirectional movement of Na (down gradient) and glucose (against)
- Epithelial cells that line SI and renal tubules
- Ex: Invokana
- Symporter
Na-Ca Exchanger (NCX) function
What type of transporter?
- Maintains low intracellular Ca levels
- Imports 3 Na (down gradient) and exports 1 Ca (against gradient)
- Antiporter
Monosaccharides are transported from intestinal lumen across enterocyte into blood stream. Which transporters and type of transport do Glu, Fru, and Gal (and Na) use?
- Glu and Gal:
- Enter enterocyte along with Na by secondary active transport (SGLT1)
- Enter bloodstream by facilitated diffusion (GLUT2)
- Fru:
- Facilitated diffusion using GLUT5 (apical) and GLUT2 (basolateral)
- Na
- Primary active transport using Na/K-ATPase (basolateral)
How is cystic fibrosis is caused by a defective CFTR gene, what does this code for and what gets built up? What clinical sx does the condition cause?
- CFTR is a chloride channel mediating active transport (ATP) of Cl from inside of cells to outside in airways
-
Causes buildup of Cl inside airway epithelial cells
- Compensated by increased Na –> NaCl
- Water pulled in to compensate salinity and decreases water content of surface mucous layer –> thicker mucous and airways susceptible to bacterial infections
What is the defect in Cystinuria and what does this cause?
What are clinical sx?
- Defect in transport responsible for uptake of dimeric AA (Cystine) and dibasic AA (Arg, Lys, Ornothine)
- Causes formation of Cystine crystals in kidney
- Present with renal cholic (intermittent abdominal pain)
How is deficient in Harnup disease and what does this lead to?
What are the clinical sx?
- Defect in non-polar/neutral AA transportation
- Trp precursor of serotonin, melatonin, niacin (NAD+)
- Transporter primarily in kidneys and intestine
- Clinical: failure to thrive in infancy, intermittent cerebellar ataxia, nystagmus, photodermatitis, photosensitivity
What are cardiotonic drugs?
How do they work?
What are they used for?
- Cardiac glycosides that are contraction inducing drugs (Oubain and Digoxin)
- Inhibit Na/K-ATPase –> Increased intracellular Na and secondary increase in Ca due to slowing of NCX –> Stronger excitation contraction of heart due to increased sarcoplasmic Ca
- Used for CHF and A-Fib
