Lipids and Membranes

Transcription

1 Lipids and Membranes Presented by Dr. Mohammad Saadeh The requirements for the Pharmaceutical Biochemistry I Philadelphia University Faculty of pharmacy

2 Lipids and Membranes I. overview Lipids are related fatty acids (esters of fatty acids with alcohol). 1. They are essential components of all living organisms with widely varied structures. 2. They are insoluble in water and soluble in organic solvents. 3. They are either hydrophobic (nonpolar) or amphipathic (containing both nonpolar and polar).

3 Lipids and Membranes II. Structural and functional diversity of lipids ** Simplest lipids, fatty acids (esters of fatty acids with alcohol), have general formula R-COOH (R represent hydrocarbon chain) these can be divided into two groups. a. Fats (saturated or unsaturated), are the ester of fatty acids with glycerol (oil) b. Waxes, are the ester with higher alcohols (cetyl alcohol). ** Complex type of lipids, including triacylglycerols, glycerophospholipids, and sphingolipids. * Phospholipid, lipids containing phosphate groups. * glycosphingolipids, lipids containing sphingosine and carbohydrate * isoprenoids, stroid, lipid vitamins, and terpenes are related to the five- carbon molecule isoprene.

4 Lipids and Membranes II. Structural and functional diversity of lipids Some function of lipids, 1. Biological membranes contain amphipathic lipids (sphingolpid). 2. Intracellular storage molecules for metabolic energy. (triacylglycerols). 3. A dipos tissue occurs under the skin and in the abdominal cavity, so they serve as thermal insulation and padding. 4. Steroid hormones regulate metabolic activities. 5. eicosanoids, regulation of blood pressure. 6. Glycosphingolipid, located in the cell surface and participate in cellular recognition. 7. They carry fat-soluble vitamins A, D, E and K.

5 Lipids and Membranes III. Fatty acids 1. Fatty acids differ from one another in 1. the length of their hydrocarbon tails, 2. the number of C-C double bonds, 3. the positions of the double bonds in the chains, and 4. the number of branches. 2. pka of fatty acid about therefore the fatty acids ionized at physiological ph. 3. Fatty acids are form detergent because they have a long hydrophobic tail and a polar head. 4. Fatty acids are joined to other molecules by an ester linkage at terminal carboxyl group.

6 Lipids and Membranes III. Fatty acids 5. saturated fatty acid don't contain C-C double bond. 6. unsaturated fatty acid, contain two or more C-C double bond. 7. Saturated fatty acids are waxy solids at RT (22 c). 8.Unsaturated fatty acids are liquids at RT (22 c). 9. The lengths of hydrocarbon tails increase, the melting points of fatty acids increase.

7 III. Fatty acids 10. The configuration of the double bonds in unsaturated fatty acids is generally cis. 11. In IUPAC, n, n indicates the lower-numbered carbon atom of each double-bonded pair.

8 Lipids and Membranes III. Fatty acids 12. Fatty acids occur in trace amount in living cells. Most fatty acids are esterified to glycerol or other backbone compounds to form more complex molecules, example: fatty acids laurate and linoleoly called lauroyl and linoleoyl ester respectively. 13. The most abundant fatty acids in animals are usually oleate (18:1), palmitate (16:0) and stearate (18:0). 12. Mammals require certain dietary polyusaturated fatty acids that they no synthesized, such as linoleate (18:2) (plant oil), and linolenate (18:3) (fish oil). Such fatty acids called essential fatty acids.

9 Lipids and Membranes III. Fatty acids

10 Saturated fatty acids

11 Unsaturated fatty acids

12 Lipids and Membranes IV. Triacylglycerols *Fatty acids are important metabolic fuels. *The oxidation of fatty acids yield more energy ( 37kJ/g) than oxidation of proteins or carbohydrates ( 16kJ/g). *Fatty acids are generally stored as neutral lipids called triacylglycerols. *Triacylglycerols (triglycerides) are composed of three fatty acyl residues esterified glycerol, a three-carbon alcohol (see figure). Triacylglycerols are very hydrophobic (*can not form bilayers), so they can be stored in cells in an anhydrous form (not solvated by water).

13 Glycerophospholipids (phosphoglyceride) two types: 1. Glycerophospholipid 2. Plasmalogens The most abundant in membranes are glycerphospholipids SUCH AS Have a glycerol backbone. The simplest Glycerophospholipids (phosphatidates), consist of two fatty acyl groups esterified to C-1 and C-2 of glycerol 3-phosphate (Table 9.2). (In general, saturated fatty acids esterified to C-1and unsaturated fatty acids esterified to C-2, (note: triglyceride, three fatty acyl groups esterified to glycerol) The phosphate group is esterified to both glycerol and another compound bearing an OH group (Table 9.2). Glycerophospholipids are amphipathic molecules, with a polar head and long nonpolar tails (Figur 9.7).

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16 Glycerophospholipids (phosphoglycerides) Glycerophospholipids are amphipathic molecules, with a polar head and long nonpolar tails (Figur 9.7).

17 Glycerophospholipids (phosphoglycerides): The specific positions of fatty acids in glycerophospholipids can be determined by using 1. phosphlipase A1 catalyze the hydrolysis of the ester bonds at C-1 and produce fatty acids 2. phosphlipase A2 (present in snake, bee, and wasp venom) catalyze the hydrolysis of the ester bonds at C-2 and produce fatty acids resulting hydrolysis RBCs (figure 9.8). 3. phosphlipase C catalzes hydrolysis of the P-O bond between glycerol and phosphate to liberate diacylglycerol (DAG) 4. phosphlipase D converts glycerophospholipids to phosphatidates (figure 9.8).

18 Glycerophospholipids (phosphoglycerides):

19 Glycerophospholipids (phosphoglycerides): Plasmalogens is one of the major type of glycerophospholipids, differ from phophatidates in having the hydrocarbon substituent on the C-1 hydroxyl group of glycerol attached by a vinyl ether linkage rather than ester linkage (figure 9.9). Plasmalogens abundant in the human central nervous system.

20 Sphingolipids: Sphingolipids are abundant in tissues of the central nervous system. Sphinglipids is sphingosine (trans-4-sphingenine), an unbrached C18 alcohol with a trans double bond between C-4 and C-5, an amino groups at C-2 and hydroxyl groups at C1 and C-3 (figure 9.10a). Types of sphingolipids: 1. Ceramide; 2. Sphingomyelins; 3. Cerebrosides; 4. Gangliosides 1. Ceramide consists of a fatty acyl group linked to the C-2 amino group of sphingosine by an amide bond (figure 9.10b). Ceramide are the metabolic precursors of all sphingolipids. 2. Sphingomyelins, contain phosphate (phospholipid), phosphocholine is attached to the C-1 hydroxyl group of ceramide (zwitterions) (figure 9-10c). Sphingomyelins are present in plasma membranes of the most mammalian cells and a major component of myelin sheaths that surround certain nerve cells.

21 Sphingolipids:

22 Sphingolipids: 3. Cerebrosides are glycosphingolipids that contain one monosaccharide residue attached by a β-glycosidic linkage to C-1 of a ceramide. Example, galactocerebrosides known as galactosylceramides, are abundant in nerve tissue and account for about 15% of the lipids of myelin sheaths (β-d-galactosyl, β-d-glucosyl residue as a head polar and non polar tail) (figure9.11).

23 Sphingolipids: 4. Gangliosides are more complex glycosphingolipid in which oligosaccharide chains containing N-acetyleneuramimic acid (NeuNAc) are attached to a ceramide. An acetylated derivative make the head group of gangliosides anionic. The structure of ganglioside, G M2 (Figure 9.12).

24 Sphingolipids: In all gangliosides, the ceramide is linked through its C-1 to a β-glucosyl residue, which in turn is bound to a β-galactosyl residue. Gangliosides are present on cell surfaces, with two hydrocarbon chains of the ceramide moiety embedded in the plasma membrane and the oligosaccharides on extracellular surface that are divers with glycoprotein. These markers provide cells with distinguishing surface markers that can serve in cellular recognition and cell-cell communication. Structures similar to the ABO blood group antigens on the surface of human cells. The composition of membrane glycosphingolipids can change during the development of malignant tumors.

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26 Steroids Steroid cholesterol (non polar) is synthesized by mammalian cells. It is an important component of animal plasma membranes, essential precursor of steroid hormones and bile salts.

27 Other biologically important lipids Many kinds of lipids not found in membranes such as 1. waxes, 2. eicosanoids, and 3. some isoprenoids. 1. Waxes are very water insoluble, high melting point, non polar ester of long-chain monohydroxylic alcohols. For example, myricyl palmitate, a major of beeswax, is the ester of palmitate (16:0) and the 30-carbon myricyl alcohol (figure 9.17) and ear wax. Waxes are widely distributed in nature provide protective waterproof coating on leaves and fruits and on animal skin, fur, feathers, and exoskeletons.

28 Other biologically important lipids 1. Eicosanoids are oxygenated derivatives of C20 polyusaturated fatty acids such asarachidionic acid. 2. Prostaglandins are ecosanoids that have cyclopentane ring (b,c,d in the figure 9.18). Pathological response Cause contraction of blood vessels Formation of blood clot Mediator of smooth-muscle contraction 3. Some isoprenoids such as the lipid vitamin A,D, E, and K.

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