Biochemistry-Membrane Lipids Flashcards

1
Q

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.

A

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).

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2
Q

What are examples of three building blocks of membrane lipids?

A

Fatty acid (palmitate), backbone (glycerol-3-P) and a head group (serine).

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3
Q

What are the four types of phospholipids?

A

*

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4
Q

How does glycolysis contribute to the variety seen in phospholipids?

A

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.

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5
Q

What are the possible polar heads that can be attached to form a phospholipid?

A

Choline, Ethanolamine, Serine, Inositol and Glycerol

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6
Q

How is a phospholipid made starting from glycerol-3-P?

A

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

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7
Q

What 2 ways can CTP activate phosphatidic acid?

A

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.

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8
Q

What phospholipids are produced based on how phosphatidic acid is activated?

A

If the head group is activated 1st: phosphatidylcholine, phosphatidylethanolamine or phosphatidylserine. If the Backbone is activated 1st: phosphatidyl inositol, cardiolipin or phosphatidyl glycerol

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9
Q

What remodeling enzymes are used to form varying phospholipids in the body?

A

Phospholipase to get rid of one nonpolar tail and acetyltransferase to add new non polar tails.

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10
Q

How is phosphatidylcholine made?

A

You start with DAG, hit it with CDP-choline and it will put choline onto DAG to form phosphatidylcholine.

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11
Q

How do you get from phosphatidylcholine to phosphatidylethanolamine to phosphatidylserine and back?

A

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.

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12
Q

How do you get phosphatidyl inositol from phosphatidic acid?

A

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.

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13
Q

How is inositol obtained in our bodies?

A

Diet or cyclization of gluc-6-P

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14
Q

What is another name for cardiolipin?

A

Diphosphatidylglycerol.

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15
Q

Show where and how membrane lipid synthesis occurs

A

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

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16
Q

What phospholipids are synthesized in peroxisomes?

A

Plasalogens (ether glycerolipids)

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17
Q

How does the distribution of different types of phospholipids vary in the membrane leaflets?

A

The outer leaflet consist of phosphatidylcholine (PC) and sphingomyelin. The inner leaflet consists of phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI).

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18
Q

What mixture makes the most fluid bilayer?

A

A mixture of saturated and unsaturated fatty acids with lots of cholesterol mixed in.

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19
Q

Ingestion of aspirin will affect what phospholipid interaction?

A

Synthesis of eicosanoids from arachadonic acid

20
Q

What phospholipid plays a role in kinase activation?

A

Phosphatidic acid

21
Q

What phospholipid plays a role in mitogenesis?

A

Lysophosphatidic acid

22
Q

What phospholipid plays a role in angiogenesis?

A

Sphingosine 1-P

23
Q

What fatty acids are at the sn-1 and sn-2 sites of PC, PE and PI?

A

*

24
Q

How are inflammatory mediators released from phospholipids in the bilayer?

A

Free radical oxidation of arachadonic acid -> Release of AA by phospholipase A2 -> isoprostane which will become inflammatory mediators like prostaglandins and leukotrienes.

25
Q

How do phospholipids help us get the things we need from the food we eat while preserving the digestive tract?

A

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

26
Q

How could you test to predict if a baby will have respiratory distress syndrome?

A

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.

27
Q

How is a glycolytic intermediate converted into plasmalogen?

A

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.

28
Q

What plasmalogens are found in myelin, in heart muscle and in platelet aggregation/inflammation?

A

Ethanolamine plasminogen = myelin, choine plasmalogen = heart muscle and C2 remodeled choline plasmalogen (PAF) = platelet aggregation/inflammation

29
Q

What happens when PAF binds to a receptor on a cell?

A

It activates a G-protein which initiates a cascade that ends up in Ca release, PKC activation, prostaglandin/thromboxane A2/leukotriene synthesis.

30
Q

What will people with Zellweger Disease be deficient in but have an over accumulation of?

A

Deficient in plasmalogens and over accumulation of VLCFA (very long chain fatty acids) due to defective peroxisomes.

31
Q

What is the key intermediate structure in the synthesis of sphingolipids?

A

Ceramides.

32
Q

What phospholipids are derived from ceramide and where are they found?

A

Sphingomyelin = PC + ceramide (nerve fiber myelination), cerebrosides = sugar + ceramide (brain). Globosides, gangliosides and sulfa tides are all derived from cerebrosides.

33
Q

How is ceramide built?

A

Serine and palmitoyl-CoA are combined by ceramide synthase

34
Q

How is spingomyeline broken down?

A

Sphingomyelinase

35
Q

What makes up a cerebroside? Where are they commonly found?

A

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.

36
Q

What are globosides?

A

Neutral ceramide oligosaccharides

37
Q

What accumulates in Tay-Sachs disease?

A

Gangliosides. These are negatively-charged ceramide oligosaccharides.

38
Q

What are sulfa tides?

A

Sulfated cerebrosides.

39
Q

What is PAPS made from?

A

Gal-Cerebroside undergoes a sulfotransferase reaction to form PAPS.

40
Q

How do cholesterols find a way to be transported in the blood?

A

LCAT (lecithin-cholesterol acyltransferase) esterifies cholesterol at sn-2 of PC.

41
Q

How does phospholipase C (PLC) use phospholipids to alter cellular activity?

A

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.

42
Q

How does the cell use phospholipases in the immune response?

A

Phospholipase A2 cleaves the sn-2 fatty acid and it goes on to make eicosanoids.

43
Q

How does cholera toxin affect our cellular components?

A

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.

44
Q

What is a good target for stopping spread of a virus from cell to cell?

A

Neuroaminidase inhibitors makes it so the virion is stuck to the infected cell because neuroaminidase can no longer cleave the haemagglutinin-sialic acid binding.

45
Q

Enzyme defect and accumulant in Tay-Sachs disease.

A

Hexosaminidase A = Gm2 ganglioside build up

46
Q

Enzyme defect and accumulant in Gaucher’s disease.

A

Glucocerebrosidase = glucocerebroside accumulation