Flashcards in Membranes and Transport Deck (26):
Glycerol backbone with a phosphate group and two fatty acids esterified to backbone.
E.g. Phosphatidylcholine (outer), phosphatidylserine (inner), phosphatidylinositol (inner)
Sphingosine backbone, with a long chain fatty acid and phosphorylcholine.
E.g. Sphingomyelin - most common SL present in OUTER leaflet
Sphingosine backbone with carbohydrate residue (instead of phosphorylcholine like on sphingomyelin).
Found in OUTER leaflet of the lipid bilayer.
Embedded in lipid bilayer. Steroid nucleus with:
(1) hydroxyl group and
(2) hydrocarbon side-chain - interacts with hydrophobic tails of membrane
Glycerophospholipid on INNER leaflet.
Used as a marker for cell apoptosis.
-healthy cells have PS on inner leaflet
-apoptotic cells display PS on outer leaflet
-Serves as tag/label for apoptotic cells
-Dying cells recognized and phagocytically removed
Deficiency: Defective Acid Sphingomyelinase enzyme (A-SMase)
A-SMase: lysosomal enzyme that breaks down sphingomyelin (SM)
-SM accumulates in lysosomes of liver, spleen, CNS, bone marrow
-Hepatomegaly, splenomegaly and Neuro damage
Integral membrane proteins
Firmly EMBEDDED in the membrane, stabilized by hydrophobic interactions with lipids.
-Polytopic Transmembrane proteins
>Integral mem proteins spanning entire lipid bilayer, contact both internal/external environment several times
>Transporters, ion channels and receptors
LOOSELY BOUND to membrane via electrostatic interactions with lipids or proteins.
TETHERED to membranes via covalent attachment to a lipid
Carbohydrate shell on outer-membrane of cell due to presence of glycolipids and glycosylated proteins.
-Protects membrane from injury/degradation
-enables better contact with other cells (good in tissue formation)
-Allows body to differentiate healthy cells from foreign/diseased cells.
ABO Blood system
RBCs have carbohydrate antigens on surface. Blood transfer must be compatible: cross match ABO type.
Incompatible transfusion: acute hemolysis, renal failure, shock
Type A —> Contains Anti-B
Type B —> Contains Anti-A
Type A/B —> No antibodies in plasma (Universal acceptor)
Type O —> Contains Anti-A and Anti-B (Universal donor)
Protein antigen on RBCs. Must be cross matched for compatibility in transfusion.
“D antigen” known as Rh factor - inherited in autosomal dominant fashion.
Rh+ individuals express D antigen. Rh- do not.
Disease in which blood of mother and fetus is incompatible because mother is Rh- and fetus is Rh+.
Mother produces antibodies to the Rh factor of the fetus during pregnancy. Antibodies can cross placenta and attack fetus - risk greater in subsequent pregnancies.
Factors that influence membrane fluidity
-Tm = Temp which membrane switch from fluid to rigid
-TTm, optimal fluidity
-T>>>Tm, membrane too fluid
(2) Lipid composition
-Saturated v unsaturated Fatty acids
-Higher saturated fatty acids = tighter packing = reduced mobility
-Higher unsaturated FA = kinks, loose packing = increased fluidity
-cholesterol in rigid membrane = increases fluidity (intercalates in FAs preventing close packing)
-cholesterol in fluid membrane = reduces fluidity (fills in gaps from kinks)
Spur Cell Anemia
Condition of elevated cholesterol. Too much cholesterol in the RBC membranes makes them rigid, reduced fluidity/flexibility. When trying to squeeze past small capillaries, their membranes lyes.
Intracellular and Extracellular Ions
Extracellular: Na+ , Cl- , Ca2+
Simple Diffusion vs Facilitated Diffusion
-small, non-polar and uncharged polar molecules diffuse across membrane (O2, N2, benzene, etc.)
-Needs transmembrane protein assistance
-Large and charged molecules (unable to cross membrane alone - Na+, Cl- , Glucose, etc.)
-Protein: ion channel or transporter
Increase in membrane potential due to influx of positively charged ions - triggers opening of voltage-gated ion channels.
E.g Sodium channel
Toxin that can block ion channels (Na+/K+ ATPase)
Used by puffer fish for defense
Primary vs Secondary Active Transport
Primary: Uses ATP directly
- P type ATPases: ATP is hydrolyzed and protein gets phosphorylated on a conserved aspartate residue (Na+/K+ ATPase)
-ABC transporters: ATP is hydrolyzed, but does NOT phosphorylation transporter (P glycoproteins)
Secondary: Use energy stored. In concentration gradient to move another molecule against its concentration gradient (E.g. SGLT, NCX)
Sodium-Glucose Transporter 1
Secondary active transporter in epithelial cells of small intestine and renal tubules.
Moves Na+ and glucose unilaterally from intestinal lumen to blood
Or from blood/urine to renal tubule.
Na+ moves downhill, providing energy for glucose to move uphill.
Na+ gradient resent by Na+/K+ ATPase
Inhibit SGLT and more glucose will be lost through urine - blood sugar goes down and increased urine output lowers blood pressure
Antiporter maintaining low levels of intracellular calcium.
Imports 3 Na+ down concentration gradient and 1 Ca2+ uphill.
Deficiency: Mutation in CFTR gene (cystic fibrosis transmembrane conductance regulator). Autosomal recessive disorder.
In the airway, Cl- cannot EXIT the cells and builds up intracellularly. Na+ enters to offset negative charge build up. Water then follows for osmotic compensation, thus dehydrating the surface mucous in the airway. Mucous becomes thick, breathing becomes difficult and leaves airways susceptible to bacterial infection.
In sweat glands, Cl- cannot ENTER the cell.
Defect in the TRANSPORT responsible for uptake of dimeric AA Cystine, and other dibasic AAs Arg, Lys and Ornithine. Autosomal Recessive disorder.
Cystine, which forms a dimmer with disulfide bonds, is not absorbed and thus builds up in the kidneys, forming Cystine crystals (kidney stones).
Manifests as “renal cholic” = abdominal pain that comes in waves and linked to kidney stones
Defect in TRANSPORT of non-polar/neutral AAs: Ala, Val, Thr, Leu and most importantly, Tryptophan.
Transporter primarily in kidneys and intestine.
Trp is a precursor for serotonin, melatonin and niacin (vitamin precursor for NAD+).
Manifests in infancy as failure to thrive. Clinical findings: ataxia, nystagmus, tremor, photodermatitis and photosensitivity.