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1 Biosynthesis of Membrane Lipids and Steroids. 2 Membrane Lipids and Steroids Phospholipids 1.Phosphatidate is a common intermediate in synthesis of.

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Presentation on theme: "1 Biosynthesis of Membrane Lipids and Steroids. 2 Membrane Lipids and Steroids Phospholipids 1.Phosphatidate is a common intermediate in synthesis of."— Presentation transcript:

1 1 Biosynthesis of Membrane Lipids and Steroids

2 2 Membrane Lipids and Steroids Phospholipids 1.Phosphatidate is a common intermediate in synthesis of phospholipids and triacylglycerols 2.Cholesterol is synthesized from acetyl-CoA 3.Regulation of cholesterol synthesis at several levels 4.Derivates of cholesterols -> bile salts, steroid hormones,…

3 3 Synthesis of Phospholipids and Triacylglycerols

4 4 Phosphatidic acid (mammalians) is synthesized in the endoplasmic reticulum and outer mitochondrial membran Phosphatidic acid mainly synthesized from dihydroxyacetone phosphate (glycolysis) Phosphatidate is a Common Intermediate in Synthesis of Phospholipids and Triacylglycerols R 1 is usually saturated R 2 is usually unsaturated

5 5 Synthesis of Triacylglycerols Synthesized in Endoplasmic reticulum of the liver Transport of TAG from liver to muscles (for energy conversion) or adipocytes (storage)

6 6 Phospholipids

7 7

8 8 Activation of Intermediate for Synthesis of Phospholipids (Cytidine diphosphate)

9 9 Synthesis of Phospholipids

10 10 Synthesis of Phospholipids

11 11 Ether Lipids are Found in Archae Bacteria

12 12 Special Ether Phospholipid PAF involved in allergic and inflammatory responses

13 13 Plasmalogen: Special case of Phosphatidycholine In many tissues plasmalogens -> minor constituents, In heart tissue nearly 50% of phosphatidylcholine contains the alkenyl ether at position sn-1.phosphatidylcholine Nervous tissues, testes and kidneys also contain significant amounts of plasmalogens. Ether-containing phospholipids can protect cells against the damaging effects of singlet oxygen, which at high concentrations can kill cells.oxygen

14 14 Sphingolipids Sphingolipids are found in plasma membrane of Eukaryotes -> Produced from Ceramides Highest concentration in central nervous system Possible role of lipids: second messangers -> i.e. initiate cell death X=H -> Ceramide

15 15 Synthesis of Sphingolipids Gangliosides Sphingolipids Cholera doxin -> binds to gangliosides -> Development of cholera (severe diarrhea) Gangliosides are crucial for binding of immune System cells to sites of injury (inflammation)

16 16

17 17

18 18 Usage of Lipids

19 19 Steroids Cholesterol

20 20 Synthesis of Cholesterol

21 21

22 22 Regulation of Cholesterol Biosynthesis Cholesterol obtained from: 1. Diet 2. Synthesized de novo Synthesis in mammals: Liver and Intestine Regulation of synthesis mainly by feedback regulation of 3- hydroxy-3-methylglutary CoA reductase (HMG CoA reductase) 1.Rate of synthesis of mRNA of reductase 2.Rate of translation of reductase 3.Degradation of reductase 4.Phosphorylation decreases activity Regulatory mechanism are modulated by receptors that sense cholesterol on blood

23 23 Transport of Cholesterol and Triacylglycerols -> Cholesterol + Triacylglycerols are transported as lipoprotein particles -> Synthesized and secreted by liver and intestine Role of protein component (Apoproteins): solubilize hydrophobic lipids + contain cell targeting signal Lipoprotein particles are classified according to their density

24 24 Core of hydrophobic lipids surrounded by a shell of more hydrophilic lipids

25 25 Triacylglycerols + Cholesterol Diet High in Triacylglycerol content (99%) -> low density Cholesterol of diet LDL is major carrier of cholesterol in blood and regulates de novo synthesis -> High LDL -> “Bad Cholesterol” -> Atherosclerosis HDL (“Good cholesterol”) is a shuttle that moves cholesterol throughout the body -> to use it or to produce hormones

26 26 Regulation of Cholesterol Biosynthesis Diet

27 27 LDL Regulates Cholesterol Metabolism Cholesterol synthesis Liver cell engaged in synthesis and secretion of VLDL Endocytosis of LDL bound to its receptor 1.Apoprotein B-100 (on surface of LDL) binds to specific receptor 2.Receptor-LDL complex initiates endocytosis 3.Vesicles fuse with Lysosomes -> Break down of Protein and Lipids (Lipase) 4.Cholesterol can be used for membrane biosynthesis or reesterfied for storage

28 28 Receptor-Mediated Endocytosis

29 29 Cholesterol Biosynthesis Blocker Potent blocker of HMG CoA reductase -> reduce level of synthesized cholesterol

30 30 Cholesterol Derivates – Bile Salts Bile salts are cholesterol derivates. -> highly efficient detergents, help to solubilize dietary lipids -> synthesized in liver, stored in gall bladder, released into small intestine Major bile salt cysteine The only way we can get rid of excess of cholesterol -> cholesterol derivates -> mainly produced bile salts !!!

31 31 Cholesterol Derivates – Steroid Hormones (Androgens)

32 32 Nomenclature of Steroid Hormones 3α or 3β hydroxy Below planeAbove plane 5α or 5β hydrogen Trans fusion Steroid hormones Cis fusion Bile salts Steroid hormones are hydroxylated by Cyt P450

33 33 Synthesis of Precursor for Steroid Hormones

34 34 Synthesis of Progesterone and Corticosteroids

35 35 Synthesis of Androgens and Estrogens

36 36 Synthesis of Vitamin D Plays an important role in Calcium and Phosphorus metabolism In the liver + kidney

37 37

38 38

39 39 Isoprenoids

40 40 β-Carotinoids

41 41

42 42


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