Membranes and Transport

Question 1

Glycerophospholipids

Answer 1

Glycerol backbone with a phosphate group and two fatty acids esterified to backbone.

E.g. Phosphatidylcholine (outer), phosphatidylserine (inner), phosphatidylinositol (inner)

Question 2

Sphingolipids

Answer 2

Sphingosine backbone, with a long chain fatty acid and phosphorylcholine.

E.g. Sphingomyelin - most common SL present in OUTER leaflet

Question 3

Glycolipids

Answer 3

Sphingosine backbone with carbohydrate residue (instead of phosphorylcholine like on sphingomyelin).

Found in OUTER leaflet of the lipid bilayer.

Question 4

Cholesterol

Answer 4

Embedded in lipid bilayer. Steroid nucleus with:

(1) hydroxyl group and
(2) hydrocarbon side-chain - interacts with hydrophobic tails of membrane

Question 5

Phosphotidylserine (PS)

Answer 5

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

Question 6

Niemann-Pick Disease

Answer 6

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

Question 7

Integral membrane proteins

Answer 7

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

Question 8

Peripheral Proteins

Answer 8

LOOSELY BOUND to membrane via electrostatic interactions with lipids or proteins.

Question 9

Lipid-anchored proteins

Answer 9

TETHERED to membranes via covalent attachment to a lipid

Question 10

Glycocalyx

Answer 10

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.

Question 11

ABO Blood system

Answer 11

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)

Question 12

Rh antigen

Answer 12

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.

Question 13

Erythroblastosis fetalis

Answer 13

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.

Question 14

Factors that influence membrane fluidity

Answer 14

(1) Temperature
- 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

(3) Cholesterol
- cholesterol in rigid membrane = increases fluidity (intercalates in FAs preventing close packing)
- cholesterol in fluid membrane = reduces fluidity (fills in gaps from kinks)

Question 15

Spur Cell Anemia

Answer 15

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.

Question 16

Intracellular and Extracellular Ions

Answer 16

Intracellular: K+

Extracellular: Na+ , Cl- , Ca2+

Question 17

Simple Diffusion vs Facilitated Diffusion

Answer 17

Simple Diffusion:

• Unaided
• small, non-polar and uncharged polar molecules diffuse across membrane (O2, N2, benzene, etc.)

Facilitated Diffusion:

• Needs transmembrane protein assistance
• Large and charged molecules (unable to cross membrane alone - Na+, Cl- , Glucose, etc.)
• Protein: ion channel or transporter

Question 18

Depolarization

Answer 18

Increase in membrane potential due to influx of positively charged ions - triggers opening of voltage-gated ion channels.

E.g Sodium channel

Question 19

Tetrodotoxin

Answer 19

Toxin that can block ion channels (Na+/K+ ATPase)

Used by puffer fish for defense

Question 20

Primary vs Secondary Active Transport

Answer 20

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)

Question 21

Sodium-Glucose Transporter 1

Answer 21

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

Question 22

NCX

Answer 22

Na+/Ca2+ Exchanger.

Antiporter maintaining low levels of intracellular calcium.
Imports 3 Na+ down concentration gradient and 1 Ca2+ uphill.

Question 23

Cystic Fibrosis

Answer 23

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.

Question 24

Cystinuria

Answer 24

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

Question 25

Hartnup Disease

Answer 25

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.

Question 26

Cardiotonic Drugs

Answer 26

Cardiac glycosides ouabain and digoxin are contraction-inducing drugs. Used in congestive heart failure.

They inhibit Na+/K+ ATPase on cardiac myocytes (heart muscle cells). Leads to increase in intracellular Na+ —> leads to increase of Ca2+ due to NCX slowing down. Increased sarcoplasmic Ca2+ = stronger contraction of heart muscle per action potential.