DLA 2 Flashcards
What’s partition coefficient?
Measure of the substance’s lipophilicity
-Relates to how well a substance partitions itself between two different immiscible substances like oil (lipid) and water at equilibrium
Give an example of partition coefficient in oil and water
A substance added to oil and water will dissolve in each. At equilibrium the chemical potential (free energy) will be the same in both phases. Partition coefficient is determined by measuring the concentration of the substance in the oil and water phases
The ratio is simply the concentration of a substance in oil divided by the concentration of the substances in water
How do we calculate partition coefficient?
Concentration of substance in oil/ concentration of substance in water
What would be the meaning of different partition coefficient values?
- A partition coefficient of 1: substance would be equally able to exist as a solute in water and in oil
- A high partition coefficient more than 1: substance is lipophilic (soluble in oil) and can pass easily through the membrane (exists mainly in oil)
- A low partition coefficient Les than 1: substance isn’t able to partition itself into the lipid phase (only soluble in water) and therefore cannot easily pass directly through the membrane (exists mainly in water )
- Use log values for aesthetics is coefficient is large/full of zeros
What would coefficient of oxygen or carbon dioxide be?
High (above 1) because they pass through the membrane directly
What would coefficient of sugars and electrolytes be?
Low (less than 1) because they are polar and interact poorly with the lipid phase of the membrane
What is a permeability coefficient?
Degree to which a substance can pass through the membrane (directly through the bilayer or through a channel or transporter)
- a fractional coefficient on a scale of 0 to 1
- 1 means maximum permeability —substance easily crosses the membrane
- 0 means no permeability- substance cannot freely pass through the membrane
What is a reflection coefficient?
This is easily a substance can cross the membrane based on its reflection
-If a substance is reflected by the barrier (does not pass through), then it’s reflection coefficient is 1
- if the substance is not reflected by the barrier(passes through) then it’s reflection coefficient is 0–> permeable substances have low (or zero) reflection coefficients
What is absorption?
Movement of solutes/fluid from lumen to blood
-Na+ is absorbed across the apical membrane in the cell via the channel epithelial sodium channel (ENaC)—> pumped out of the cell into the basolateral space by the Na-K ATPase—> whole process is regulated by the selective opening and closing of specific channels in the apical membrane
What is secretion?
Movement of solutes/fluid from blood into the lumen
-Apical potassium/chloride channels open and allow potassium/chloride to move from from the cell into the lumen of the structure
What are at the sides of epithelium?
The cells are joined by tight junctions which delineate the apical and basolateral membranes
- some tight junctions are truly tight—> not allow substances to pass between cells
- Other epithelia are less tight abd termed ‘leaky’ epithelia—> flux of paracellular flow of substances
Explain epithelial transport
Solutes must be transported across two membranes in order to reach the blood from the lumen or vice versa
- Apical membrane is in contact with the luminal space
- Basolateral membrane is in contact with the interstitium and blood
- Different transporters and pumps are present on each membrane giving rise to a difference between membranes (polarity)
The vectorial transport of substances- a combination of transporters and pumps on the basolateral and apical membranes
-Major role for epithelial cells is the secretion and/or absorption of solutes and fluid —> achieves secretion or absorption of fluid by transporting solutes and setting up an osmotic gradient that 2ater can flow down
What are the classifications of lipids?
- Simple lipids-triacylglycerol -hydrophobic
- Complex lipids(contain non-lipid component)-amphipathic
- Derived lipids- fatty acids, cholesterol
What are the types of unsaturated fatty acids?
Monounsaturated (MUFA)
Polyunsaturated fatty acids (PUFA)
What are saturated fatty acids?
No double binds
Long chain fatty acids 12-20 C atoms, e.g. palmitic acid, stearic acid
Describe saturated fatty acids
- longer chain length, close packing and lower mobility in membranes
- Lipids with saturated fatty acids are solid
- Palmitic acid (16C) and stearic acid (18C)
- longer chain length rich in myelin
- Nutrition pearl: limit dietary saturated fatty acid content for cardiovascular health
What are the monounsaturated fatty acids ?
- Oleic acid (18:1)
- Olive oil rich in oleic acid
- Mediterranean diet
Describe polyunsaturated fatty acids
More number of double bonds
- more fluidity of membranes
- multiple kinks prevent close parking
Two families
- omega 3: a-linolenic acid: Eicosapentaenoic acid and DHA
- omega-6: linoleic acid and arachnidonic acid
Nutrition pearl:
- more omega-3 and less omega 6 fatty acids
- Lower dietary omega-6: omega 3 fatty acid ratio
How does the essential fatty acid, linoleic acid converted to arachodonic acid?
- Desaturation (addition of a double bonds)
2. Elongation (addition of 2 C atoms)
How does alpha linoleic acid(C18:3, omega-3) become docosahexanoic acid?
First becomes eicosapentaenoic acid(C20:5, omega 3)
Then becomes docisahexanoic acid(C22:6, omega- 3)
What is the purpose of eicosanoids?
Eicosanods from EPA are cardioprotective
-DHA important for neural/brain development and for vision
What are the essential fatty acids?
-Humans cannot add double bind after C-9(starting from carboxyl end)
- Linoleic acid (omega-6) and a-linolenic acid (omega-3) dietary essential fatty acids
- cannot be synthesized
- must be provided in diet.
-Nutritional deficiency: scaly dermatitis, rough and dry skin, loos of hair
What are trans fatty acids?
‘Trans’ conformation; NO kink in structure
-Limited mobility (act like saturated fatty acids)(compare unsaturated fatty acids with ‘cis’ bonds)
- Nutrition Pearl: NO ‘trans’ fatty acids
- increase LDL cholesterol and risk of heart disease
Partially (artificially) hydrogenated lipids like margarine, fried foods, baked goods…
Describe cholesterol
27-C atom
-Cyclopentanoperhydrophenanthrene (steroid ) ring
- Amphipathic ring
- hydrophilic hydroxyl group
- hydrophobic group
Regulation of membrane fluidity
What are the functions of cholesterol?
-Cell/plasma membrane (both leaflets)
- Precursor of bile acid/bile salt synthesis in liver
- efficient intestinal digestion and absorption of dietary lipids
- Precursor of steroid hormones
- Cortisol and aldosterone in adrenal cortex
- Sex steroids: estrogen and progesterone in ovaries; testosterone in Testes
Precursor for synthesis of vitamin D in skin
How much of the diet are TAGs ?
About 90%-95% of dietitian lipids are TAGs
- fats(butter)
- oils
What are the functions of TAGs?
Storage form of energy in adipose tissue
- hydrophobic
- 70kg adult stores 15kg as adipose TAG (fat)
- Sources if energy during fasting
Not components of membrane
Summarize the saturated fatty acids(palmitic acid (C16) and stearic acid(C18)) functions
Components if TAG, phospholipids and glycolipids (decrease membrane fluidity)
Summarize monounsaturated fatty acid functions (oleic acids C18)
Components if TAG, phospholipids and glycolipids
Summarize the polyunsaturated fatty acids functions(omega-3 and omega-6 fatty acids)
Components of TAG, phospholipids and glycolipids (increase membrane fluidity )
Summarize the functions of omega-3 fatty acids (alpha-linoleic acid, eicosapentansrnoic acid, docosahexaenoic acid)
Function: components of TAG, phospholipids and glycolipids (increase membrane fluidity
Summarize the function of omega 6 fatty acids (linoleic acid, arachadonic acid)
Components of TAG, phosohlipids abd glycolipids (increase membrane fluidity)
What are the functions of the essential fatty acids (alpha-linolenjc acid, linoleic acid)?
Components of TAG, phospholipids and glycolipids (increase membrane fluidity)
Summarize the functions of cholesterol
Cell membrane (both leaflets), precursor of steroid hormones, Vit D and bile acids
What are the complex lipids?
Based on non-lipid component(phospholipids and glycolipids)
Phospholipids- glycerophospholipids and sphingophospholipid
Glycolipid- cerebrosides, sulfatides, globosides, ganglioside
Complex lipids are
Amphipathic
Contrast saturated and unsaturated fatty acids
Unsaturated fatty acid susceptible to free radical damage (reactive oxygen species)
What is phosphatidic acid ?
Bonding between hydroxyl of phosphate group with hydroxyl of glycerol carbon 3 results in phosphatidic acid. Phosphatidic acid is building block of phospholipids found in found in cell membrane.
Phosphatidic acid is NOT found in cell membranes
W(at combines to make phospholipids?
Phosphate group, diacylglycerol —> phospholipid with phosphatidic acid
Give examples ofglycerophospholipids
Phosphatidylserine
Phosphatidylcholine
Phosphatidylethanolamine
Phosphatidylinositol
What is the function of cardiolipin?
- Only in inner mitochondrial membrane
- Anticardiolipin antibodies: autoimmune disorders(SLE)
Summarize the asymmetry of phospholipid distribution
ECM= phosphatidylcholine = PC +sphingomyelin=
ICM= phosphatidylserine= PS, phosphatidylethanolamine = PE, phosphatidylinositol= PI
What is phosphatidylcholine?
Aka lecithin:most abundant
- in both leaflets of membrane layer
- more abundant in outer leaflet
What are the functions of phosphatidylethanolamine and phosphatidylserine(apoptosis)
-inner leaflet of phospholipids bilayer (cytosolic side)
Where are phosphatidylinositol and phosphatidylinositol and biphosphate (PIP2)?
- inner leaflet of bilayer
- second messengers: inositol triphosphate (IP3) and diacylglycerol (DAG)
What are the functions of Dipalmitoylphosphatidylcholine (DPPC)?
Lung surfactant
- decreases surface tension of alveolar fluid
- prevents alveolar collapse
- Respiratory distress syndrome: collapse of alveoli
- premature infants
- chronic smokers (smoking destroys type II cells)
- Amniotic fluid Lecithin-Sphingomyelin ratio(L/S ratio)
- L/S ratio> 2: mature fetal lung and low risk of RDS
- L/S ratio <1.5: immature fetal lung
- Artificial surfactant fluids with DPPC/Maternal steroid injections
What group of lipids does DPPC belong to?
Glycerophospholipid
Describe sphingophospholipid (sphingomyelin)
Sphingosine (C-18)
Sphingosine with fatty acid forms ‘ceramide’
Sphingosine with fatty acid-phosphatase-choline
Myelin sheath around neurons
Describe glycolipids
- Amphipathic
- Sphingosine and fatty acid: non polar
- Carbohydrate: polar head group
- outer leaflet of plasma/cell membrane
- glycocalyx with glycoproteins on outer leaflet of cell membrane
- function as receptors
- myelin sheath of nerves
What is the composition of cerebrosides?
Sphingosine+ fatty acid + monosaccharide
What is the composition of sulfatide?
Sphingosine+ fatty acid+ monosaccharide + saulfate
What is the composition of globoside?
Sphingosine+ fatty acid + oligosaccharide
What is the composition of a ganglioside?
Sphingosine + fatty acid+ oligosaccharide (with NANA) Tay-Sachs disease
What are the functions of cerebrosides, sulfatode, globoside, and ganglioside?
Outer leaflet of plasma (cell) forms glycocalyx
All mammalian cells have a …
Plasma membrane formed by a phospholipid bilayer containing embedded proteins
The plasma membrane has been described as a fluid mosaic of lipids and protein molecules because of their movement laterally
Summarize the fluid mosaic model
The modified fluid mosaic model describes very small membrane patches or “lipid rafts” with dynamic assembles of unique protein and lipid composition which separates them from other fluid membrane areas
Differentiate the types of lipid rafts
Short lived: “planar lipid rafts” rich in:
-Cholesterol
- Glycosphingolipids
- Sphingomyelin
Long-lived: Caveolae are lipid rafts forming an invagination of the plasma membrane stabilized by specific proteins (caveolins)
Lipid rafts can facilitate signal transduction and a virus infection
What is the lipid composition of the outer leaflet of the membrane?
Contains mainly, phosphatidyl choline and sphingomyelin. Glycosphingolipids and less amounts of phosphatidylethanolamine
What is the lipid composition of the inner leaflet of the cell membrane?
Contains mainly phosphatidylethanolamine. Phosphatidylserine, phosphatidylinositol and PIP2 and less of phosphatidylcholine
Where are glycolipids and glycoproteins usually found? What are
In the outer layer and form a glycocalyx
