Shortly after an infant is born, blood oxygen levels decrease rapidly and X-ray shows collapsing of the lungs. What genetic defect may be affecting this infant.
Respiratory distress syndrome involves a decrease in lung surfactant. Surfactant decreases the surface tension in alveoli, allowing the lungs to re-expand after contraction. The genetic mutation is most likely in type II alveolar cells that secrete DPPC (dipalmitoylphosphatidylcholine).
What are examples of three building blocks of membrane lipids?
Fatty acid (palmitate), backbone (glycerol-3-P) and a head group (serine).
What are the four types of phospholipids?
How does glycolysis contribute to the variety seen in phospholipids?
Glycolysis can contribute two backbone components: glycerol-3-P and DHAP. The glycerol-3-P goes on to become glycerophospholipids and the DHAP goes on to become etherglycerophospholipids and can be further manipulated to become sphingolipids.
What are the possible polar heads that can be attached to form a phospholipid?
Choline, Ethanolamine, Serine, Inositol and Glycerol
How is a phospholipid made starting from glycerol-3-P?
Step 1) Addition of 2 fatty acid-CoA molecules by FA binding protein Step 2) Addition of a polar head group with CTP and cytidyl transferase
What 2 ways can CTP activate phosphatidic acid?
It can activate the head group and the head group reacts with DAG or it can activate phosphatidic acid and it reacts with the head group.
What phospholipids are produced based on how phosphatidic acid is activated?
If the head group is activated 1st: phosphatidylcholine, phosphatidylethanolamine or phosphatidylserine. If the Backbone is activated 1st: phosphatidyl inositol, cardiolipin or phosphatidyl glycerol
What remodeling enzymes are used to form varying phospholipids in the body?
Phospholipase to get rid of one nonpolar tail and acetyltransferase to add new non polar tails.
How is phosphatidylcholine made?
You start with DAG, hit it with CDP-choline and it will put choline onto DAG to form phosphatidylcholine.
How do you get from phosphatidylcholine to phosphatidylethanolamine to phosphatidylserine and back?
Phosphatidylcholine can form phosphatidylethanolamine via the enzyme phosphatidylethanolamine methyltransferase (PEMT). PE can for PS via the enzyme PS synthase and can go beck to PE via PS decarboxylase.
How do you get phosphatidyl inositol from phosphatidic acid?
1.) Hit phosphatidic acid with CTP to form CDP-diacylglycerol (DAG) 2.) phosphatidylinositol (PI) synthase will allow PI to attack and replace CDP on DAG to form phosphatidylinositol.
How is inositol obtained in our bodies?
Diet or cyclization of gluc-6-P
What is another name for cardiolipin?
Show where and how membrane lipid synthesis occurs
1.)FA binding protein binds FFA to cystolic face of rER. 2.) CoA transferase adds CoA to FA. 3.) FA reacts with glycerol-3-P to form phosphatidic acid 4.) Phosphatase removes Pi to form DAG 5.) CDP-Choline reacts to form phosphatidylcholine
What phospholipids are synthesized in peroxisomes?
Plasalogens (ether glycerolipids)
How does the distribution of different types of phospholipids vary in the membrane leaflets?
The outer leaflet consist of phosphatidylcholine (PC) and sphingomyelin. The inner leaflet consists of phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI).
What mixture makes the most fluid bilayer?
A mixture of saturated and unsaturated fatty acids with lots of cholesterol mixed in.
Ingestion of aspirin will affect what phospholipid interaction?
Synthesis of eicosanoids from arachadonic acid
What phospholipid plays a role in kinase activation?
What phospholipid plays a role in mitogenesis?
What phospholipid plays a role in angiogenesis?
What fatty acids are at the sn-1 and sn-2 sites of PC, PE and PI?
How are inflammatory mediators released from phospholipids in the bilayer?
Free radical oxidation of arachadonic acid -> Release of AA by phospholipase A2 -> isoprostane which will become inflammatory mediators like prostaglandins and leukotrienes.
How do phospholipids help us get the things we need from the food we eat while preserving the digestive tract?
They work with bile salts to emulsify TAGs and cholesterol esters. They solubilize cholesterol to minimize gallstone formation. They form micelles that transport TAGs and cholesterol esters in circulation
How could you test to predict if a baby will have respiratory distress syndrome?
Take a sample of amniotic fluid and look for PC and sphingomyelin levels because these are the phospholipids that make up lung surfactant. If they are low, you may have a problem.
How is a glycolytic intermediate converted into plasmalogen?
DHAP is acylated with acyl-CoA by DHAP acyltransferase at C1. Alkyl DHAP synthetase then removes that acyl group and attaches a fatty acid that has been reduced by NADPH and no longer has a carbonyl. The C2 carbonyl is then reduced to an alcohol, a fatty acid is added to C2 and C3 is dephosphorylated. This creates a DAG-like molecule that can react with activated polar head groups (CDP-ethanolamin or CDP-choline). After the polar head group is added to C3, the fatty acid on C1 is desaturated to form a plasmalogen.
What plasmalogens are found in myelin, in heart muscle and in platelet aggregation/inflammation?
Ethanolamine plasminogen = myelin, choine plasmalogen = heart muscle and C2 remodeled choline plasmalogen (PAF) = platelet aggregation/inflammation
What happens when PAF binds to a receptor on a cell?
It activates a G-protein which initiates a cascade that ends up in Ca release, PKC activation, prostaglandin/thromboxane A2/leukotriene synthesis.
What will people with Zellweger Disease be deficient in but have an over accumulation of?
Deficient in plasmalogens and over accumulation of VLCFA (very long chain fatty acids) due to defective peroxisomes.
What is the key intermediate structure in the synthesis of sphingolipids?
What phospholipids are derived from ceramide and where are they found?
Sphingomyelin = PC + ceramide (nerve fiber myelination), cerebrosides = sugar + ceramide (brain). Globosides, gangliosides and sulfa tides are all derived from cerebrosides.
How is ceramide built?
Serine and palmitoyl-CoA are combined by ceramide synthase
How is spingomyeline broken down?
What makes up a cerebroside? Where are they commonly found?
Ceramide monosaccharides (gluco-cerebroside and galacto-cerebroside). They are found in myelin lipids, the plasma membrane of glial cell and are intermediates in glycolipid synthesis.
What are globosides?
Neutral ceramide oligosaccharides
What accumulates in Tay-Sachs disease?
Gangliosides. These are negatively-charged ceramide oligosaccharides.
What are sulfa tides?
What is PAPS made from?
Gal-Cerebroside undergoes a sulfotransferase reaction to form PAPS.
How do cholesterols find a way to be transported in the blood?
LCAT (lecithin-cholesterol acyltransferase) esterifies cholesterol at sn-2 of PC.
How does phospholipase C (PLC) use phospholipids to alter cellular activity?
It cleaves the Pi group off of C3 to make DAG and IP3 from PIP2. DAG and IP3 go on to increase Ca levels and turn genes on.
How does the cell use phospholipases in the immune response?
Phospholipase A2 cleaves the sn-2 fatty acid and it goes on to make eicosanoids.
How does cholera toxin affect our cellular components?
It binds to Gm1 gangliosides on the outer-membrane surface of intestinal mucosa cells. Binding allows the toxin to enter the mucosa cell. The toxin ribosylates the G-alpha subunit and makes it constitutively active and cAMP levels increase. This causes Cl- levels to increase, water loss and diarrhea.
What is a good target for stopping spread of a virus from cell to cell?
Neuroaminidase inhibitors makes it so the virion is stuck to the infected cell because neuroaminidase can no longer cleave the haemagglutinin-sialic acid binding.
Enzyme defect and accumulant in Tay-Sachs disease.
Hexosaminidase A = Gm2 ganglioside build up
Enzyme defect and accumulant in Gaucher's disease.
Glucocerebrosidase = glucocerebroside accumulation