46
Figure, 21-23 Head group attachment 1. Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head group Membrane phospholipids: Glycerophospholipids sphingolipids Smooth ER Mitochondria inner membrane

Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

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Page 1: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-23Head group attachment

1. Backbone Glycerol, sphingosine (serine)2. Fatty acid ( Phosphatidic acid,

DAG)3. Hydrophilic head4. Exchange head group

Membrane phospholipids:Glycerophospholipidssphingolipids

Smooth ERMitochondria inner membrane

Page 2: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-24Two strategies for forming phosphodiester bond

Page 3: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

p.826

FIGURE 21–25 Origin of the polar head groups of phospholipids in E. coli.

Page 4: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

p.826

Page 5: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Kinase--Signal transduction

Figure, 21-26Polar head in eukaryotes

Mitochondria inner membraneHelp enzymes for energy metabolism--complex IV and V, apoptosis (cytochrome C release)

Page 6: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-27 Yeast (Eukaryotic cells –major source of PE and PC)

p.828

PS

PE

Page 7: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

p.828

Figure, 21-27

S-adenosylmethionine (SAM)

S-adenosylhomocysteine

PC

Page 8: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Fig. 21-28 a head group exchange (only in mammals—ER)

Page 9: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-28 bPhosphatidylcholine in mammalsPE (the same strategy)

Salvage pathwayCholine reused (strategy 2)

Page 10: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

p.829

Figure, 21-29 summary of the pathways for synthesis of major phospholipid

Mutation in ethanolamine kinase(easily shocked)Eliminate phosphatidylethanolamine Synthesis: less in membraneTransient paralysis: electrical stimulation

In mammals(no CDP-diacylglycerol and serineto PS)

In liver only

Page 11: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-30Ether lipid, Plasmalogenplatelet-activating factor

Half of the heart phospholipid

Page 12: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head
Page 13: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head
Page 14: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head
Page 15: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Head group

Page 16: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

peroxisome

Page 17: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-31Sphingolipids

2nd big groupLung surfactant

Page 18: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Step 1

18 C amine

O-

Page 19: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Step 2

Step 3

Step 4

(SER)

GlycolipidGlycosidic linkage

Page 20: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Golgi

Page 21: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-32Not required in diet

Cell membraneSteroid hormone Bile acids

Page 22: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-33Cholesterol biosynthesisIn liver

6C

5C

30C

condensation

polymerization

cyclization

Page 23: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-34Synthesis of mevalonate

cytosol

Rate-limiting step Release 3CoA(membrane of the SER)

Page 24: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-35Mevalonate to activated isoprene

Use 3 ATPRelease 1 CO2

Page 25: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-36Squalene

10C

15C

30C

Page 26: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

(rose oil)

Page 27: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head
Page 28: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-37Ring closure

20 stepsMethyl group migration and removal

Mixed function oxidase

plants

Page 29: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-38Cholesteryl esters

Stored or in lipoprotein particles

Page 30: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure 21-39Plasma Lipoproteins-Lipid transport(LDL)

Page 31: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure 21-39B

Page 32: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

TABLE 21-1

p.836

Page 33: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

TABLE 21-2

p.837

Page 34: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure21-40Lipoprotein andLipid transport

apoE

apoCII--lipase

apoB100

apoB100

apoA-I

Page 35: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure 21-42Uptake of cholesterol by receptor-mediatedendocytosis

Page 36: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure21-40Lipoprotein andLipid transport

apoA-I

SR-BIABC1

Page 37: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure 21-41

Surface of nascent HDL

Chylomicron and VLDL remnants

Page 38: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-44Regulation of cholesterol

dp

p

Inhibit transcription

Page 39: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-43SREBP (sterol regulatory element-binding protein) activationSCAP: SREBP cleavage-activating protein—binds to cholesterol and other sterols

HMG CoA reductaseLDLR

Page 40: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-45Inhibitors of HMG-CoA reductaseCholestyramine-resin binds to bile acids-prevent reabsorption

Competitive inhibition of HMG-CoA reductase

statin

Page 41: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-48 isoprenoidPrenylationProetins are anchored to cellular membrane

Page 42: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-46Steroid hormones from cholesterol

Increase gluconeogenesisAnd TAG cycle

Page 43: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Figure, 21-47Side chain cleavage

Adrenal cortexmitochondria

Hydroxylation and cleavage

Page 44: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Fatty liver:

TAG formation and export imbalanceExtensive accumulation of TAG—cirrhosis1. Free fatty acids increase in plasma, then to liver accumulation2. Block production of plasma lipoproteins a. apolipoprotein synthesis b. lipoprotein c. phospholipid d. secretory pathway

Ethanol—fatty liverEthanol is converted to be acetaldehyde by alcohol dehydrogenase and NADH is producedExcess NADH inhibit CAC and increase lipogenesis (cholesterol)

Page 45: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head
Page 46: Figure, 21-23 Head group attachment 1.Backbone Glycerol, sphingosine (serine) 2. Fatty acid ( Phosphatidic acid, DAG) 3. Hydrophilic head 4. Exchange head

Homework: How insulin regulates lipid metabolism?