Lipid Chemistry 2023-2024 PDF

# Lipid Chemistry ## The Genius in Biochemistry **Dr. Mohamed Agha** **2023 - 2024** ## Contents - Introduction - 2 - Classification - 2 - Simple lipids - 3 - Complex lipids - 5 - Phospholipids - 5 - Glycolipids - 7 - Derived lipids - 8 - Steroids - 8 - Sterols - 8 - Bile Acids - 10 - Bile sal...

# Lipid Chemistry ## The Genius in Biochemistry **Dr. Mohamed Agha** **2023 - 2024** ## Contents - Introduction - 2 - Classification - 2 - Simple lipids - 3 - Complex lipids - 5 - Phospholipids - 5 - Glycolipids - 7 - Derived lipids - 8 - Steroids - 8 - Sterols - 8 - Bile Acids - 10 - Bile salts - 10 ## Lipid Chemistry - Lipids are heterogeneous group of organic compounds related to fatty acid. - They contain C, H and O. they may also contain P, N and S. ### Common properties of lipids 1. Relatively insoluble in water. 2. Soluble in Non-Polar (fat solvents) as Ether, Benzene, Chloroform and Acetone. 3. They can be utilized by living organisms. 4. They contain F.A or derived from F.A. ## Classification of lipids ### Simple lipids - F.A + Alcohol - Glycerol - True Fats - Higher M.W monohydric alcohol - Waxes ### Complex (Compound) lipids - F.A + Alcohol + Another group ### Derived lipids - F.As - Alcohols - Higher Alcohols - Steroids - Carotenoids - Fat soluble vitamins (KEDA) - Phosphate Phospholipids - Alcohol - Carbohydrate Glycolipids All contain Sphingosine - Glycerol Sphingosine - Glycero Phospholipids - Sphingo Phospholipids - Neutral - Acidic - Cerebrosides - Galacto Cerebrosides - Gluco Cerebrosides - + Sulfate - Sulfatides - + NANA - Gangliosides ## Simple Lipids = True fats (Neutral fats) - Esters of Glycerol + various F.As. They are usually different. - Glycerol + F.A → Mono Acyl glycerol (MAG). - Glycerol + 2 F.A → Di Acyl glycerol (DAG). - Glycerol + 3 F.A → Tri Acyl glycerol (TAG) = Triglycerides (TG) - Tri acyl glycerol - Simple: contain one kind of F.As in the 3 positions. - Mixed: contain 2 or more different F.As. ### Glycerol - Trihydric Alcohol, containing 3 OH, colorless, syrupy, liquid, sweet and very hygroscopic. ### Fatty Acids - Aliphatic monocarboxylic organic acids, obtained by natural fats & oil hydrolysis. - F.A in natural fats contain an **Even** number of Carbon atoms (2 – 24). - All of them possess a long hydrocarbon chain and terminal carboxyl group. - RCOOH + H₂C-OH + HC-OH + H₂C-OH → H₂C-O-C-R + HC-0-C-R' + H₂C-0-C-R" + 3H₂O - R' - R" - Three fatty acids - Glycerol - Triglyceride ## Classification of F.As ### A. According to chain length: 1. Low (short chain) F.A: Contain 10 C atoms or less (2 – 10 Carbons). - Acetic Acid (2C) - CH₃ - COOH - Butyric Acid (4C) - CH₃-CH₂-CH₂ - COOH 2. High (long chain) F.A: Contain more than 10 C atoms. - Palmitic Acid (16 C) - CH₃-(CH₂)₁₄ - COOH - Stearic Acid (18 C) - CH₃-(CH₂)₁₆ - COOH ### B. According to Saturation & Unsaturation: 1. Saturated F.A (contain no double bonds) as Butyric, Palmitic, Stearic. 2. Unsaturated F.A (contain one or more double bonds) - Mono Unsaturated FA (contain one double bond) - Oleic acid - 18:1;9 (ω9) - Nervonic acid - 24:1;15 (ω9) - Poly Unsaturated FA PUFA (contain more than one double bond) - Usually double bonds are separated by methylene groups (-CH₂-) - Linoleic acid - 18:2;9,12 (ω6) - a- Linolenic acid - 18:3;9, 12, 15 (ω3) - Arachidonic acid - 20:4; 5, 8, 11, 14 (ω6) - Arachidonic acid is precursor to prostaglandins. - counting Double bonds from COOH end. - counting Double bond from CH3 end. - Oleic acid - 18:1;9 (ω9) - CH3-(CH₂)₇ – CH = CH - (CH₂)₇ – COOH - Nervonic acid - 24:1;15 (ω9) - CH₃-(CH₂)₇ – CH = CH - (CH₂)₁₃ – COOH - Linoleic acid - 18:2; 9, 12 (ω6) - CH3-(CH₂)₄ - CH = CH - CH₂ - CH = CH - (CH₂)₇ - COOH ### C. Biological classification: 1. Essential F.As: - These are PUFA, can't be synthesized in mammals. - Must be obtained in diet. - As Linoleic acid and Linolenic acid. 2. Non Essential F.As: - These are saturated or monounsaturated F.As. - Mammals can synthesize them from other precursors. 3. Relatively Essential: - As Arachidonic Acid found in Animal fat and peanut oil. - Synthesized (Non-Essential) in the Body from Linoleic Acid. - It Becomes Essential (not synthesized) if linoleic is missing in the diet. ## Biological Importance of true Fats: 1. Reserve foods in animals and plants. In animals they are found as depot fat in subcutaneous tissue which is mobilized during starvation to produce Energy so its amount is variable (True fats → Variable Element of fat). 2. Most compact form of Energy stored (1 gm fat → 9.3 Kcal). 3. Supporting material in some parts of the body as around the kidneys. - Eating foods rich in Monounsaturated FA as Olive oil (Oleic Acid) - Improve blood cholesterol level. - Decrease risk of heart diseases. - Decrease risk of Type 2 diabetes. - **Omega-3 FA** - Oily fish (Salmon), vegetable oils, nuts. - Integral part of cell membrane and affect receptors function. - They have anti-inflammatory action, regulate blood pressure, cholesterol, TG, so they protect from heart diseases. - **Arachidonic acid** - Important role in cell membrane fluidity & transport. - Generates bioactive lipids (Prostaglandins, Thromboxanes, Leukotrienes and Lipoxins) that perform important physiological role. ## Complex Lipids ### I- Phospholipids - They are membrane components, amphipathic, Ionic compounds. - They are 2 classes: (constant Element of fat) - Glycero phospholipids. - Sphingo phospho lipids. #### A. Glycerophospholipids: - The precursor of these compounds is L-glycerol - 3-phosphate. - This compound has an asymmetric C & can exist either in (D) or (L) form. - The isomer found in nature is the (L) form. - F.A in the 1st position → Saturated, High F.A. - F.A in the 2nd position → Unsaturated, High F.A. - Phospholipids are Amphipathic: - Phosphoryl bases → Polar hydrophilic heads (Ionizable heads). - Hydro carbon chain → Non Polar hydrophobic tail. #### Types of Glycero phospho lipids: 1. Phosphatidic Acid - Simplest form of phospho Glycerols & the Precursor of other members. - Present mainly as intermediate compound during synthesis of phospho Glycerols and TAG. - Occurs in very small amounts in the cell. - It has no Base. - CH₂OH + HO--C--H + CH₂-O-P-O- - CH₂-O-C-R¹ + R²-C-O-C-H + CH₂-O-P-O- - C-Palmitic - C-Palmitic - C-P. Choline - Di Palmitoyl Lecithin - L-Glycerol 3-phosphate - Phosphatidic acid 2. Lecithin (Phosphatidyl Choline): - Most abundant phosphoglycerides in plants and animals. - The base is Choline. It is present in animal's cell membrane. - **N.B:** Di Palmitoyl Lecithin: in this phospholipid position 1, 2 of glycerol are occupied by Palmitate. - It is the major lipid component of lung surfactants which is the Extra cellular fluid lining the Alveoli. - Surfactants decrease surface tension of fluid layer therefore prevent alveolar collapse. - Surfactants absence from the premature infants' lungs cause Respiratory Distress Syndrome (RDS). 3. Cephalin (Phosphatidyl Ethanolamine): - Another abundant phospho glyceride, found in animal cell membrane. - The base is Ethanolamine. There are 3 and 2 cephalin. - Cephalin is one of the important blood clotting factors. 4. Phosphatidyl Serine: - Cephalin like and present in many tissues. - The base is the amino acid Serine. 5. Lipositol (Phosphatidyl Inositol): - The polar head is the cyclic hexose sugar Alcohol Inositol (Myoinositol). - 2 or 3 moles of phosphate may be present in Inositol phosphatide. - In Brain and Muscles it contains 3 moles of phosphoric Acid (1, 4, 5). - Micelles - hydrophilic group - hydrophobic group #### B. Sphingo phospholipids: - Contain Sphingosine instead of glycerol + Higher FA as lignoceric Acid + Phosphoric Acid + Base. - Important membrane components in plant and animal cells. - Present in large amount in Brain & Myelin of Nervous tissue. - Amide group of sphingosine linked to long chain saturated or monounsaturated FA by Amide linkage. - The resulting compound is called Ceramide (Parent structure of all Sphingolipids). - The most Abundant are Sphingomyelins. - Their polar head is Phosphate + Choline (Base). - Sphingosine + Phosphate + High FA → Ceramide Phosphate - Base - Base - Amide Linkage - Polar Head ## II- Glycolipids (Glyco Sphingo lipids) - Neutral Glycolipids (Cerebrosides) - Acidic Glycolipid - Galacto Cerebrosides + Sulfate at C6 of Galactose → Sulfatides - Gluco Cerebrosides + one or more Sialic Acid (NANA) → Gangliosides - Glycolipids are widely distributed in every tissue of the body particularly in Nervous tissue such as Brain. - They occur in the outer leaflet of plasma membrane. - They have a role in cell communication. ## Derived Lipids | | | | | | | |---|--------------------------------|----------------------|---------------------------|---------------------|--------------------------------------| | 1 | Fatty Acids | Glycerol | Alcohols (other than glycerol) | Steroids | Carotenoids | | 6 | Fat soluble vitamins (KEDA)| |---|---|---|---|---|---| - They possess the general physical characteristics of lipids. - They are either derived from simple and compound Lipids (1, 2, 3) or associated with lipids (4, 5, 6). ## Steroids - They have similar cyclic nucleus known as Steroid nucleus (Sterane Ring). - It Resembles cyclo pentano per hydro phenanthrene ring. - Simple hexagonal ring denotes a completely saturated 6 carbon ring → it is not Benzene ring. - There is Methyl group at C₁₀ makes C₁₉ & Methyl group at C₁₃ make C₁₈. - Cyclopentano-perhydrophenanthrene (steroid) nucleus - Steroids | | | | | | |----|--------------------------------|------------------------------------|------------------------------------|---------------------| | 1 | Sterols | Bile Acids and Salt | Steroid Hormones (Sex - Cortical) | Vitamins D | | 2 | | | | Saponines & Cardiac glycoside| ### I. Sterols #### Animal sterols - Cholesterol - Its derivative → 7-dehydro cholesterol #### Plant sterols - Ergosterol - 22-dihydro ergosterol This group of steroids has - OH at C₃ → It is an alcohol. - Aliphatic side chain at C₁₇ #### A. Animals sterols: - **1. Cholesterol:** - Bio Medical importance: - Main sterol in human Body (Nervous tissue, Brain, Bile, supra renal glands). - Major constituent of plasma membrane. - Precursor of sex hormones, cortical hormones, Vitamin D & bile acids. - Sources: - Formed in Body from Acetyl CoA. - Diet: Egg yolk, meat, liver, Brain. (only in Animal fats) - Cholesterol is a solid 27 C alcohol that contains Sterane Ring and has a double bond between C₅ and C₆. (C₅ = C₆) - It is Amphipathic → play structural role in membrane and outer layer of Lipoproteins. #### 2. 7-dehydro cholesterol: - 7-dehydro cholesterol - C₅=C₆ & C₇=C₈. - (Pro Vitamin D₃) - (Stored under Skin) #### B. Plant sterols: - **1. 22-Dihydro ergosterol (Pro Vitamin D₄)** - C₅=C₆ & C₇=C₈. - Extra methyl group (CH₃) at C₂₄. - **2. Ergosterol (Pro Vitamin D₂)** - C₅=C₆ & C₇=C₈. - Extra methyl group (CH₃) at C₂₄ - Double bond between C₂₂ and C₂₃. - Ergocalciferol (Vitamin D₂) may be made by photolysis from plants. - Both vitamins D₂ and D₃ are of equal potency. ## II- Bile Acids - They are hydroxy derivatives of Cholanic acid. - They are obtained in the liver by - Oxidation of cholesterol at C₂₄. - Removal of the last 3 carbon atoms. - They are the end products of Cholesterol catabolism in the body because the body can't break down the steroid nucleus. ### Bile Acids | | | | |---|---|--------------------------------| | 1 | Primary | | | | - Cholic Acid: | 3, 7, 12 Tri hydroxy Cholanic Acid. | | | | Glyco Cholic acid. | | | | Tauro Cholic acid. | | | - Cheno deoxy cholic Acid: | 3, 7 di hydroxy Cholanic Acid. | | | | Glyco cheno deoxy Cholic acid. | | | | Tauro cheno deoxy Cholic acid. | | 2 | Secondary | | | | - Deoxy Cholic Acid: | (from Cholic Acid) | | | | 3,12 di hydroxy Cholanic Acid | | | - Lithocholic Acid: | (form cheno deoxy Cholic Acid) | | | | 3 mono hydroxy Cholanic Acids | - Primary Bile acids can be conjugated with Glycine or Taurine. - Secondary Bile Acids are produced by action of intestinal Bacteria on primary Bile Acids - 1. De conjugation from Glycine or Taurine. - 2. 7- De hydroxylation. - Bile Salts = Primary Bile Acids + Glycine or Taurine + Na⁺ or K⁺.