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

Figure, 21-24 Two strategies for forming phosphodiester bond

FIGURE 21–25 Origin of the polar head groups of phospholipids in E FIGURE 21–25 Origin of the polar head groups of phospholipids in E. coli. p.826

p.826

Figure, 21-26 Polar head in eukaryotes Kinase-- Signal transduction Mitochondria inner membrane Help enzymes for energy metabolism --complex IV and V, apoptosis (cytochrome C release)

Figure, 21-27 Yeast (Eukaryotic cells –major source of PE and PC) PS PE p.828

Figure, 21-27 PC p.828 S-adenosylmethionine (SAM) S-adenosylhomocysteine PC p.828

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

Figure, 21-28 b Phosphatidylcholine in mammals PE (the same strategy) Salvage pathway Choline reused (strategy 2)

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 membrane Transient paralysis: electrical stimulation In liver only In mammals (no CDP-diacylglycerol and serine to PS) p.829

Figure, 21-30 Ether lipid, Plasmalogen platelet-activating factor Half of the heart phospholipid

Head group

peroxisome

Figure, 21-31 Sphingolipids 2nd big group Lung surfactant

O- Step 1 18 C amine

Step 2 (SER) Step 3 Step 4 Glycolipid Glycosidic linkage

Golgi

Figure, 21-32 Not required in diet Cell membrane Steroid hormone Bile acids

Figure, 21-33 Cholesterol biosynthesis In liver condensation 6C 5C polymerization 30C cyclization

Figure, 21-34 Synthesis of mevalonate cytosol Rate-limiting step Release 3CoA (membrane of the SER)

Figure, 21-35 Mevalonate to activated isoprene Use 3 ATP Release 1 CO2

Figure, 21-36 Squalene 10C 15C 30C

(rose oil)

Figure, 21-37 Ring closure Mixed function oxidase plants 20 steps Methyl group migration and removal

Figure, 21-38 Cholesteryl esters Stored or in lipoprotein particles

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

Figure 21-39B

TABLE 21-1 p.836

TABLE 21-2 p.837

Figure21-40 Lipoprotein and Lipid transport apoA-I apoB100 apoE apoB100 apoCII--lipase

Figure 21-42 Uptake of cholesterol by receptor-mediated endocytosis

Figure21-40 Lipoprotein and Lipid transport apoA-I SR-BI ABC1

Chylomicron and VLDL remnants Figure 21-41 Chylomicron and VLDL remnants Surface of nascent HDL

Figure, 21-44 Regulation of cholesterol dp p Inhibit transcription

Figure, 21-43 SREBP (sterol regulatory element-binding protein) activation SCAP: SREBP cleavage-activating protein— binds to cholesterol and other sterols HMG CoA reductase LDLR

statin Figure, 21-45 Inhibitors of HMG-CoA reductase Cholestyramine-resin binds to bile acids -prevent reabsorption Competitive inhibition of HMG-CoA reductase statin

Figure, 21-48 isoprenoid Prenylation Proetins are anchored to cellular membrane

Figure, 21-46 Steroid hormones from cholesterol Increase gluconeogenesis And TAG cycle

Figure, 21-47 Side chain cleavage Adrenal cortex mitochondria Hydroxylation and cleavage

Fatty liver: TAG formation and export imbalance Extensive accumulation of TAG—cirrhosis Free fatty acids increase in plasma, then to liver accumulation Block production of plasma lipoproteins a. apolipoprotein synthesis b. lipoprotein c. phospholipid d. secretory pathway Ethanol—fatty liver Ethanol is converted to be acetaldehyde by alcohol dehydrogenase and NADH is produced Excess NADH inhibit CAC and increase lipogenesis (cholesterol)

FIGURE 10-18 Arachidonic acid and some eicosanoid derivatives FIGURE 10-18 Arachidonic acid and some eicosanoid derivatives. Arachidonic acid (arachidonate at pH 7) is the precursor of eicosanoids, including the prostaglandins, thromboxanes, and leukotrienes. In prostaglandin E1, C-8 and C-12 of arachidonate are joined to form the characteristic five-membered ring. In thromboxane A2, the C-8 and C-12 are joined and an oxygen atom is added to form the six-membered ring. Leukotriene A4 has a series of three conjugated double bonds. Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin and ibuprofen block the formation of prostaglandins and thromboxanes from arachidonate by inhibiting the enzyme cyclooxygenase (prostaglandin H2 synthase). 45

Homework: How insulin regulates lipid metabolism?