W4L2 Flashcards
Iron uptake into cells
- Fe+3-loaded transferrin binds to cell surface receptor (Transferrin Receptor) at neutral pH (pH 7.4)
- Transferrin (with receptor) internalizes into cell via Endocytosis
- pH of endosome lumen becomes acidic and Fe+3 dissociates
- throughout endosome, there is drop in pH
- transferrin is still bound to receptor, but iron not attached - Apo-transferrin (no Fe+3 bound to it) dissociates from Transferrin Receptor at neutral pH (after recycling back to the plasma membrane)
Please Note: Transferrin Receptor has different affinities for transferrin depending on pH and whether (or not) transferrin is bound to Fe+3.
- transferrin with Fe+3: high affinity with receptor at neutral pH
- transferrin without Fe+3: high affinity with receptor at acidic pH
- transferrin without Fe+3: low affinity with receptor at neutral pH
Note: Recycle the same protein and pumps on the endosomal membrane maintains the pH
Anemia
Lack of red blood cells or hemoglobin
Caused by blood loss
Caused by decreased red blood cell production
- Iron Deficiencies in the diet
Caused by increased destruction of red blood cells
- Hemolytic anemias
Treatment with blood transfusion or extra iron in the diet
Hemochromatosis
Iron overload
Affects liver, heart and endocrine organs
Hereditary forms as well as non-hereditary forms
Severe forms result from a hepcidin resistant ferroportin
Hepcidin comes from the liver. Liver makes it
Absorbs 2-3 times more iron than needed
Treatment by getting rid of the blood
Lipid Transport
Absorption is not straight forward through our intestinal tract
Proper absorption requires emulsification (bile action)
Transport in body requires transport vehicles
Dietary Lipid Absorption
- Bile salts from liver coat the fat
- one side of salt is hydrophilic (stays within the solution), the other side of the salt is hydrophobic (binds to the fat) - Pancreatic lipase and collipase break down fats into monoglycerides and fatty acids stored in micelles
- Monoglycerides and fatty acids move out of the micelles and enter intestinal cells by diffusion. Fatty acids are hydrophobic so will just go across plasma membrane
4.Cholesterol is transported into cells as well. Cannot just diffuse across membrane
- Absorbed fats combine with cholesterol and proteins in the intestinal cells form chylomicrons
- Chylomicrons are made in the smooth ER
- Chylomicron then goes through the Golgi apparatus
- Golgi apparatus secretes it - Chylomicrons are removed by the lymphatic system (lacteal to vena cava)
- Because: The distance bw capillary cells do not allow the large chylomicrons to make it across. The junctions are too tight. Thus, they need to go through lacteals, which are looser
Lipoprotein Structure
Made up of:
- apolipoprotein
- cholesterol
- triglyceride
- phospholipids
This is transported throughout lacteals and blood stream
Lipid Transport Post-Absorption
- From the lacteals to the blood stream, lipids travel in chylomicrons throughout the body
- Adipose cells can extract lipids using lipoprotein lipases
- Chylomicrons go to fat cells, which extract what they want, which is lipids - Then, Chylomicrons remnants (like apolipoprotein, triglycerides, cholesterol) are metabolized by the liver
- Excess cholesterol and triglycerides can be stored by the liver
- Liver can also send lipids to the rest of the body in water-soluble carriers.
– Adipose can send lipids to the liver in similar carriers
Types of Lipoproteins
All contain diff amounts of: triglyceride, phospholipid, cholesterol, protein
From intestine
- Chylomicron (mostly triglyceride)
- Remember, once the chylomicron remnants go to the liver, the liver will repackage them with more things like proteins and then sends it back out
Made by liver
- VLDL
- LDL
Returned back to liver
- HDL
From lowest to highest protein content (highest to lowest triglyceride content):
1. Chylomicron
2. VLDL - very low density lipoprotein
3. LDL - low density lipoprotein
4. HDL - high density lipoprotein
Internalization of LDL
- Ligand (LDL) binds to membrane receptor at cell surface
- Receptor-ligand migrates to clathrin-coated pit
- Triskelion causes clathrin coated vesicle
- Triskelion is a form of clathrin
- Many triskelions come together to make a clathrin coat
- btw, transferrin receptor does the same thing by going to clathrin-coated pit, followed by endocytosis - Endocytosis into Clathrin-coated Vesicle
- Clathrin-coated Vesicle loses clathrin coat
- Receptors and ligands inside the vesicle separate at the endosome (is acidic)
- Ligands go to lysosomes or Golgi for processing
- Transport vesicle containing the receptors inside move to the cell membrane
- Transport vesicle and cell membrane fuse (membrane recycling).
- Exocytosis
- So the receptors go back to membrane surface
Familial Hypercholesterolemia (FH)
Genetic inheritance- severity dependent on # of mutant genes
LDL receptor gene is impacted
- If you do not have enough LDL receptor to process lipids, it will stay in your bloodstream
Heterozygotes- 2x LDL in blood - develop cardiovascular disease
Homozygotes- 4-6x LDL in blood - heart attack in 20s
Lipid Bilayer
Dynamic structure composed of phospholipids
Continuously being replaced through recycling
Membranes contain lipids, protein, cholesterol, glycolipids and glycoproteins
Recycling between existing membranes (grows by inserting individual components like proteins and lipids)
Compositions vary depending on type of cell
Membrane Compositions
of diff membranes
- Liver membrane
- about 50/50 lipid and protein, very little carbohydrate - Erythrocyte membrane
- about 50/50 lipid and protein, very little carbohydrate - Myelin membrane
- lots of lipid (79%), little protein, even less carbohydrate - Mitochondrial inner membrane
- mostly protein (76%), some lipid (24%), no carbohydrate (bc not located at cell surface)
Asymmetry of Lipid Bilayer
Inner and outer leaflets have different lipids types
- diff lipid (phospholipid) concentration
Asymmetry provides curvatures of membranes and directs overall shape of cell or organelle
Curvature:
Membrane can be saturated or unsaturated
- Saturated lipids = pack tighter
- Unsaturated lipids = have a kink, will stick out, will not pack as tightly, take up more space so more curvature
Membrane lipids
- Glycerolipids aka glycerophospholipids
- glycerol base + phosphate + 2 fatty acid chains - Sphingolipids
- sphingosine - Glycerosphingolipid
- sphingosine with glucose - Sterols
- i.e. cholesterol
Types of Glycerophospholipids
Phosphatdiyl + R group
R groups:
- Net negative charge - Inositol (PI), Serine (PS)
Inositol and serine are both neutral. But when you add it to a net negative phosphate, it is overall net negative
phosphatidylinositol and phosphatidylserine have net negative charge
- Neutral charge - Choline (PC), Ethanolamine (PE)
Choline and ethanolamine are both positive.
Phosphatidylcholine and phosphatidylethanolamine are net neutral
