Lipids PDF

## Lipid Chemistry ### Lipids - Organic compounds insoluble in water but soluble in organic solvents i.e., ether, benzene, acetone, and chloroform. ### Biomedical Importance: 1. Source of energy (Lipids have a high energy value). 2. Supply body with: - Fat soluble vitamins (vit. K, E, D and A...

## Lipid Chemistry ### Lipids - Organic compounds insoluble in water but soluble in organic solvents i.e., ether, benzene, acetone, and chloroform. ### Biomedical Importance: 1. Source of energy (Lipids have a high energy value). 2. Supply body with: - Fat soluble vitamins (vit. K, E, D and A). - Essential Fatty acid (Linoleic and a Linolenic acids). 3. Present in the body in 3 compartments: Plasma, adipose tissue, and cell membranes. ### Classification: - **Simple lipid**: Esters of FA with alcohols. - **Compound/Conjugated Lipid**: Simple lipids conjugated with another group. - **Derived lipid**: Products of hydrolysis of lipids or substance associated with lipids in nature. ### Fatty Acids (FA) R-COOH - **Def**: Mono carboxylic organic acids, mostly contain even number of carbons. - **Occurrence**: - Esterified with alcohols: In natural fat, oils, and waxes. - Unesterified: In plasma carried on albumin (FFA). ### Numbering of the Carbon Skeleton of FA 1. Starting from the carboxyl group: - Give COOH No. 1 then proceed to the terminal CH3, position of = denoted by A. - α, β, γ: the 1st carbon following COOH is a then proceed to the terminal CH3. 2. Starting from the terminal methyl group (omega "w" carbon): The terminal methyl carbon is given 01 then proceeds to COOH group. ### Classification of Fatty Acids (FA): 1. **According to number of carbons**: Even chain FA and odd chain FA 2. **According to saturation**: Saturated (SFA) and unsaturated (USFA) 3. **According to length of the chain**: short chain FA, medium chain FA, long chain FA and very long chain FA #### Saturated FA (SFA) - Contains No double bonds. #### Unsaturated FA (USFA) - Contains 1 or more double bonds. |Chain Type | FA Type | | Chain Type| FA Type | |:---:|:---:|:---:|:---:|:---:| |Short chain FA C2-6| Acetic acid C2 | | Very long chain FA C24 or more | Lignoceric acid C24 | | |Butyric acid C4 | | | | | Medium chain FA C8-10 | | | | | | Long chain FA C12-22 | Palmitic acid C16 | | | | | | Stearic acid C18 ||| | | #### Most Important FAs: - **Palmitic and Stearic acids** are the most important FAs. Why? They are widely distributed in diet. - What is the commonest FA in animal tissues? **Answer:** Paimitic acid #### Sources of SFA: - Animal fat as cream and butter - vegetables products as coconut and palm oils. #### Biomedical importance of SFA: - ↑ SFA leads to ↑ cholesterol → Tatherosclerosis → ↑ incidence of coronary heart disease (CHD). ### Unsaturated FA contain 2 types of double bonds: 1. **Cis type**: - Groups at the Same side of the double bond. - Allow bending of the chain at the double bond ↓Melting temperature so, they are liquids at room temperature. 2. **Trans type**: - Groups at the opposite side of the double bond. - FA containing trans double bonds are linear and solid at room temperature. **NB**: Naturally occurring USFA contain double bonds of the cis type. **NB**: SFA are also linear and solid at room temperature. ### Trans FA: - Produced during hydrogenation of vegetable oils into margarine. - Sources: Baked food and cakes. - Biomedical importance: ↑ cholesterol → ↑ atherosclerosis → ↑ incidence of coronary heart disease (CHD). ### Classification of FA according to No. of double bonds 1. **Monoenoic (Monoethenoid) FA**: - Contain only 1 double bond in their structure as: - Palmitoleic (16:1,07) - Oleic (18:1,9) - Present in animal and vegetable fat as olive oil. - Importance: Plasma cholesterol→ ↓ Atherosclerosis and Coronary heart disease (CHD). 2. **Polyenoic (Polyethenoid) FA or PUFA**: - Contain more than 1 double bond in their structure. - Classified according to the No. of double bonds into diethenoid, triethenoid.....etc. - PUFA are classified according to the position of the 1st double bond in relation to o carbon into 03, 06, 07 and 09 FA. #### 06 PUFA: - PUFA having the 1st double bond at carbon 6 in relation to w carbon. - **Examples**: - Linoleic acid (18:2) → Parent FA (precursor of the family). - Arachidonic acid (20: 4) - Linoleic acid is the precursor of other members of this group (Parent FA) - Source: Nuts, olives and different oils as sunflower, cotton seed, linseed, and corn oil - Importance: Plasma cholesterol→ ↓ Atherosclerosis and Coronary heart disease (CHD). #### 03 PUFA: - PUFA having the 1st double bond at carbon 3 in relation to w carbon. - **Examples**: - a Linolenic acid (18:3) → Parent FA (precursor of the family). - a linolenic is the precursor of other members of this group (Parent FA). - Source: Present in plant oil as flax seed and canola and fish oil. - Importance: intake of 03 PUFA↓ incidence of coronary heart disease..... why? 1. Cholesterol → ↓ Atherosclerosis and Coronary heart disease (CHD). 2. ↓ BP (blood pressure). 3. ↓ Plasma TAG (triacylglycerol). 4. Tendency of thrombosis. ### Most important Unsaturated FAs: | Double bonds | Name | Example | |:---:|:---:|:---:| |1 | Monoethenoid FA | Palmitoeleic and Oleic | |2 | Diethenoid FA | Linoleic | |3 | Triethenoid FA | a Linolenic | |4 | Tetraethenoid FA | Arachidonic | ### Nutritional Classification of FA: **a. Essential FA**: - Def.: FA can't be synthesized inside the body and should be supplied in diet. - Essential FAs are: - a linolenic (Precursor of 3 family). - Linoleic (Precursor of 06 family). - NBs: - Other members of 03 and 26 families are formed from a linolenic and linoleic by desaturation and elongation. - Arachidonic becomes essential in absence of linoleic acid. - Importance of essential FA: - Provide arachidonic acid for synthesis of eicosanoids - Formation of healthy cell membrane - Structure of lipotropic factors - Deficiency of essential FA leads to: - Children: Retardation of growth and dermatitis. - Adults: Fatty liver and sterility. **b. Non-Essential FA**: - Def.: FA which can be synthesized inside the body. - Examples: The rest of the FA i.e., palmitic, stearic ... etc. ### Eicosanoids - Physiologically active compounds formed from C20 PUFA as arachidonic acid. - Arachidonic acid is liberated from membrane phospholipids by phospholipase A2 or synthesized from the essential fatty acid linoleic acid by desaturation and chain elongation. ### Classification: | Eicosanoid Type| | |:---:|:---:| | Cyclic Eicosanoids (Prostanoids) | | | - Prostaglandins (PG)| | | - Prostacyclins (PGI)| | | - Thromboxanes (TX) | | | Non-cyclic Eicosanoids | | | - Leukotriens (LT) | | | - Lipoxins (LX) | | ### Nomenclature: - 1st 2 letters are the abbreviation. - The 3rd letter indicates the type i.e. A, B, C, D, E ....etc. - Subscript number indicates the No. of double bonds i.e. PGE2. #### Cyclic compounds: - Formed from arachidonic acid, by the action of the enzyme prostaglandin H synthase. This enzyme has 2 activities: cyclooxygenase (COX) and peroxidase. - COX is present in 2 isoforms, COX-1 and COX-2: - COX-1: constitutive enzyme found in most tissues (mainly in gastric mucosa, platelets, vascular endothelium, and kidney). - COX-2: inducible enzyme and is generated in response to inflammation activated by macrophages and monocytes. #### Acyclic compounds: - Including leukotrienes (LT) and the lipoxins (LX). - These are formed from from C20 PUFA (arachidonic acid) by the action of lipoxygenase (LOX). ### Synthesis of Eicosanoids from Arachidonic acid: | | | |:---:|:---:| | **Phospholipids** | | | - Lipoxygenase | | | - Prostacyclins (PGI2) | | | - Prostacyclin synthase | | | - Leukotrienes (LTA4) | | | - Lipoxins (LXA4) | | | **Arachidonic acid** | | | **Phospholipase A2**| | | **Steroid Lysophospholipids** | | | - Prostaglandin H synthase | | | - Prostaglandin (H) (PGH2) | | | - Thromboxane synthase | | | - Thromboxanes (TXA2) | | | **Other prostaglandins** | | | **X NSAID** | | ### Effects of Some Eicosanoids | **Type** | **Site of Synthesis** | **Main Functions** | |:---:|:---:|:---:| | PGE2 | Most tissues | - Vasodilatation - Smooth muscle relaxation. In bronchi it relieves bronchial asthma. - Mediator of inflammatory reactions which protect the body against infection with production of vasodilatation (redness, hotness, pain and swelling). | | PGF2α | Most tissues | - Vasoconstriction - Smooth muscle contraction (in bronchi it may cause bronchoconstriction; in the uterus it is used in induction of labor).| | TXA2 (Thromboxane A2) | Platelets | - Vasoconstriction - ↑ Platelet aggregation | | PGI2 (Prostacyclin 12) | Endothelium of blood vessels| - Vasodilatation - Inhibits platelet aggregation. - Normally there is a balance between the action of prostacyciins and thromboxanes. | | Leukotrienes | Leukocytes, platelets, and mast cells | - They stimulate inflammatory reactions - Components of slow-reacting substance of anaphylaxis (SRS-A) (severe allergic reaction that may result in respiratory distress (bronchoconstriction or spasm), low blood pressure and shock). | | Lipoxins | Arterial walls | - Anti-inflammatory. - Decrease immune response. | ### Clinical Aspects (Anti-inflammatory and Anti-allergic Drugs) 1. **Steroidal anti-inflammatory drugs (SAID):** Inhibit phospholipase A2 activity (decrease availability of arachidonic acid) e.g., hydrocortisone, prednisone, and betamethasone. 2. **Nonsteroidal anti-inflammatory drugs (NSAID):** They inhibit prostaglandin production by inhibiting cyclooxygenase, they include: - **Aspirin:** more potent inhibitors against COX-1 than COX-2. It inhibits the cyclooxygenase, thus decreasing the synthesis of prostaglandins which act as messenger molecules in the process of inflammation. - **Other NSAIDs:** inhibit cyclooxygenase by binding noncovalently to the enzyme e.g., indomethacin and ibuprofen, they produce inhibition of the both COX-1 and COX-2. 3. **Singulair**: - Leukotriene receptor antagonist. - Blocks the action of leukotriene on cysteinyl leukotriene receptor - Relieves bronchospasm and inhibits allergic pathway (used to treat bronchial asthma allergies). **Explain why**: 1. Aspirin is anti-inflammatory and antipyretic. 2. Steroids are used in treatment of bronchial asthma. 3. NSAID is contra-indicated in bronchial asthma. ### 1. Simple Lipids - Def.: Esters of FA with alcohol. - Classified: According to the type of alcohol into: |Simple Lipids| Simple Lipid Type | |:---:|:---:| | **Neutral Fat (TAG)** | Esters of 3 FA with glycerol | | **Waxes** | Esters of FA with higher alcohols | ### Neutral Fats - **Triacyl glycerol (TAG) or Triglycerides** - Glycerol: is the alcohol present in TAG. - Fatty acids: FAs present in TAG are usually of different types (SFA and USFA) so called mixed TAG. - Neutral fats (TAG) are classified into 2 subgroups: - **Oils**: - Have low melting temperature. - Liquids at room temperature due to their content of USFA. - i.e., sunflower, cotton seed, linseed, and maize oils. - **Solid fats**: - Have high melting temperature. - Solid at room temperature due to their high content of SFA. - i.e., butter and margarine. ### Waxes: - Def.: Esters of long chain FA with long chain alcohols. - Site: Trunks of trees and fur of animals. - Function: Acts as a protective coat. - Examples: - True wax (Bee's wax): Esters of palmitic acid (16C) with mericyl alcohol (30C). - Cholesterol esters: Lanolin (in hair). - Vit A (Retinol) esters. - Vit D (Calciferol) esters. ### 2. Conjugated Lipids: - Def.: Simple lipids conjugated with another group. - Classified into: - A. Phospholipid: Containing phosphate. - B. Glycolipid: Containing carbohydrate. ### Phospholipids - Classified according to the alcohol present into: - A. **Glycerophospholipid (Glycerophosphatides):** Containing glycerol. - B. **Sphingomyelin:** Containing sphingosine (sphingol). #### A. Glycerophospholipid (Glycerophosphatides): - Phospholipids containing glycerol as alcohol. - They are derivatives of phosphatidic acid. 1. **Phosphatidic acid**: - Diacylglycerol phosphate. - FA at position 1 is SFA and at position 2 USFA. - Formed during synthesis of TAG and phospholipid. 2. **Lecithin (Phosphatidyl choline)**: - Formed of phosphatidic acid + choline. 3. **Cephalin (Phosphatidyl ethanolamine)**: - Formed of phosphatidic acid + ethanolamine. 4. **Phosphatidyl serine**: - Formed of phosphatidic acid + serine. 5. **Phosphatidyl Inositol (Lipositol)**: - Formed of phosphatidic acid + Inositol. 6. **Plasmalogens:** - Resembles lecithin and cephalin but contains fatty alcohol instead of FA at position 1. 7. **Cardiolipins (Diphosphatidyl glycerol):** - Formed of 2 molecules of phosphatidic acid connected by 1 molecule of glycerol. - Hydrolytic products: 4FA + 3 Glycerol + 2 Phosphate. 8. **Phosphatidyl glycerol**: - Formed of phosphatidic acid + glycerol. ### Hydrolysis of Glycerophosphatides - Phospholipases: Hydrolyzes different phospholipids. | Phospholipase Type | | |:---:|:---:| | Phospholipase A1| | | Phospholipase A2 | | | Phospholipase C | | | Phospholipase D | (Not in animal body) | - **Snake venom causes death.......why?** - **Answer:** As it contains lecithinase (phospholipase A2), when injected into blood converts phospholipids in cell membrane of RBCs to lysophospholipids → Hemolysis. ### B. Sphingomyelin: - Present in myelin sheath of brain and in cell membranes. - Contain the alcohol sphingosine (sphingol) which contains 18 carbon atoms. - FA is linked to sphingosine by amide bond forming ceramide. - Ceramide + phosphate + choline = sphingomyelin. ### Importance of Phospholipids: #### A. Common functions: ACEPH A 1. Amphipathic molecules as they contain non-polar groups as FA side chains and polar groups as glycerol, phosphate, serine, ethanolamine, choline and inositol so they form micelle in water 2. Cell membrane and membrane fluidity. - As phospholipids are amphipathic, they form phospholipid bilayer. - TUSFA → kinks due cis double bonds → keeping the FA away from each other→ ↑membrane fluidity. - ↑ SFA → Interact strongly with each other →↓ Fluidity. 3. Emulsification of fat (fractionation of large fat globule into fine droplets to increase the surface area and make fat easily digested). 4. Plasma lipoprotein formation. 5. Hydrotropic substances, so prevent precipitation of cholesterol as cholesterol Stones. 6. Arachidonic acid for synthesis of eicosanoids is obtained from cell membrane phospholipid. #### b. Specific functions: 2L 3P BC 1. Lecithin provides choline for synthesis of acetylcholine (neurotransmitter) 2. Lecithin as lung surfactant: - Lung surfactant is naturally secreted material by pneumocytes and formed of dipalmitoyl lecithin (DPL). ### 3. Derived Lipids - Def.: Produced by hydrolysis of simple or conjugated lipids or associated with lipids in nature. - Includes: - 1. FA - 2. Alcohols: glycerol, Sphingosine - 3. Steroids - 4. Carotenoids - 5. Fat soluble vitamins (Vit. K, E, D and A) ### Steroids: - Compounds containing steroid nucleus (cyclo pentano perhydro phenanthrene "CPPP"). | | | |:---:|:---:| | **Sterols**| | | **Steoids** | - Bile acids | | | - Steroid hormones | #### Classified into: 1. **Sterols**: - a. Zoosterols: in animals as cholesterol. - b. Phytosterols: in plants. - c. Mycosterols: in yeasts and fungi. #### Cholesterol: - **Sources**: - Exogenous (dietary): brain, gonads, egg yolk Liver, and meat - Endogenous: Apart from RBCs every cell can Synthesize its own cholesterol - **Structure**: - Most important sterol. - Contain 27 carbons. - OH at C3 and double bond Between C5 and C6. - **Building units:** Acetyl CoA (active acetate). #### Forms: - Non-esterified (free cholesterol) which is polar. - Esterified with FA to form cholesterol ester (CE) which is non-polar. #### Distribution of cholesterol: - Widely distributed in all tissues. - Higher concentrations in the nervous tissue, liver, adrenals, gonads, skin, and adipose tissue. #### Plasma cholesterol: - Synthesized by the liver. - Normal range: 120-200 mg/dl (30% as cholesterol and 70% as cholesterol ester). - Site: Nervous tissues (Myelin sheath), Gonads and adrenals. #### Excretion: - Mainly in the form of bile salts. #### Importance: Formation of 1. Bile acids and bile salts (in liver). 2. Steroid hormones (in adrenals and gonads). 3. Cholesterol moderates membrane fluidity.... Why? - At high temperature: Prevents free movement of FA tail → ↓ Fluidity. - At low temperature: Prevents close packing of phospholipid → ↑ fluidity and ↓ gel Formation. 4. Vit D3 (Cholecalciferol) - **Synthesis in body** - Cholesterol - 7 dehydrogenase Liver - Provitamin D3 - 7-Dehydrocholesterol - Under the skin - Vitamin D3 - Cholecalciferol ### Hazards of hypercholesterolemia: - Predisposes to atherosclerosis and coronary heart diseases (CHD). - Gall bladder stones and xanthelasma (cholesterol deposits in the eye lid) - Phytosterols: presents in plants and are not physiologically important. - Mycosterols: present in yeast and fungi as Ergosterol which gives vitamin D2 ### Steroid Hormones | | | |:---:|:---:| | **Sex Hormones** | | | - **Male Sex Hormones (Androgens) C19** | | | - Testosterone | | | - **Female Sex Hormones** | | | - **Estrogens C18** | | | - Estradiol E2 | | | **Corticoids C21** | | | - Glucocorticoid | | | - Cortisol | | | - Mineralocorticoid | | | - Aldosterone| | | **Progesterone C21** | | | - Progesterone| | ### Glycolipids - Formed of ceramide (sphingosine + FA) attached to carbohydrates. - Includes Cerebrosides, Sulfolipids and Gangliosides. 1. **Cerebrosides**: - Formed of ceramide + - Glucose (glucocerebroside) - Galactose (galactocerebroside) 2. **Sulfolipids (sulfatides):** - Formed of ceramide + galactose 3 sulfate. 3. **Gangliosides**: - Formed of ceramide + complex carbohydrate radicals. ### Importance of glycolipids: Found in - Brain tissues, myelin sheath and cell membrane of RBCS - Cell membrane receptors - Recognition properties towards ligand as hormones **Q1: Enumerate choline containing lipids:** - Lecithin - Plasmalogen - Sphingomyelin - Sphingomyelin - Glycolipids **Q2: Enumerate sphingolipids:** - Cerebrosides - Sulfolipid - Gangliosides