Lecture 7: Fatty Acids & Lipids PDF

Lecture 7 Dr. Dina Nada  Lecture outline Fatty acids Lipids ▪ What are fatty acids ▪ Nature of lipids ▪ Classification of FAs ▪ Importance of lipids ▪ Classification of lipids ▪ Importance of FAs I- Simple Lipids ▪ Gene...

Lecture 7 Dr. Dina Nada  Lecture outline Fatty acids Lipids ▪ What are fatty acids ▪ Nature of lipids ▪ Classification of FAs ▪ Importance of lipids ▪ Classification of lipids ▪ Importance of FAs I- Simple Lipids ▪ General properties II- Compound Lipids ▪ Nomenclature of FAs III- Substances associated with lipids ▪ Derivatives of FAs  Fatty acids Fatty acids are long-chain hydrocarbon molecules containing a carboxylic acid moiety at one end At physiological PH it is readily ionized and thus carries –ve charge but still hydrophobic  Classification of fatty acids May be classified by the body’s need for them into: Essential (can’t be synthesized by the body and must be obtained from the diet e.g. linoleic & linolenic ) Non-essential (can be synthesized by the body) May be classified by degree of saturation with hydrogen atoms into: Saturated (No double bonds): Formula CH3 (CH2)n COOH Mono- or polyunsaturated (has one or more double bonds) Polyunsaturated fatty acids (linoleic & linolenic) are essential : because there are no human enzymes that can introduce a double bond except between the ninth carbon and COOH carbon Addition of double bonds decrease the melting point, therefore unsaturation enhances fatty acid fluidity  Importance of essential fatty acids 1- Normal growth 2- Structure of phospholipids and cholesterol esters 3- Vegetable oils e.g. corn oil is rich in essential fatty acids 4- Arachidonic acid (20C) (semi-essential) is a precursor of a group of physiologically important compounds called “eicosanoids”  General Properties of Fatty Acids Solubility: 1. Lower members are soluble in H2O 2. Increasing the chain, decreases the solubility 3. FA more than 10 carbon atoms are insoluble in H2O, soluble in fat solvents Melting points: 1. Saturated FA have high melting points, so solids at room temperature 2. Unsaturated FA is low, so they are oils at room temp  Cis and trans isomerism The presence of a double bond in a FA gives rise to a cis- trans isomerism a- cis double bond: ▪ Nearly all naturally occurring fatty acids have the double bond in the cis configuration b- trans double bond: ▪ FA behave more like saturated FAs ▪ They elevate serum LDL and increase the risk of coronary heart diseases  FAs nomenclature Fatty acids carbon atoms are numbered starting at the COOH terminus. Carbon 2 & 3 are always referred as α & β respectively. The methyl carbon atom at the distal end of the chain is called the ω carbon. Naming of Fatty Acids: 1- Common Name: It is the name by which the fatty acid is known with. 2-Systemic name: Is derived from the no of carbons in the hydrocarbon chain. Then changing the suffix e with oic Examples: C18 saturated fatty acid is called Octadecane Ocatadecanoic C18 with dB is called Octadecene Octadecenoic Oct=8, Dec=10 3- Δ-System: In this case the no before the Δ denote the no of carbons in the chain and the no of dB, respectively The no after the Δ indicate the position of double bonds. Examples: 18 Δ0 denotes a C18 fatty acid with no dbs 18:1 Δ9 denotes a C18 fatty acid with 1db Cis 18:1 Δ9 means that there is a cis db at C9 Trans 18:2 Δ9,12 means that there is 2 trans dbs at C9 & C12 4- ω–system: (denoting position of 1st db from the terminal side of the chain): The carbon of the terminal methyl group is called the ω-carbon regardless of the chain length Examples: ω-3 fatty acid means that there is a db at C3 from the methyl terminus ω-6 fatty acid means that the db is at C6 from the methyl terminus  Nomenclature & Structure Palmitic acid: 4 3 2 1 CH3CH2CH2(CH2)9CH2CH2CH2COOH ω1 ω2 ω3 γ β α 1) Hexadecanoic 2) 16 Δ0 Palmitoleic cid: CH3(CH2)5CH=CH(CH2)7COOH 1) Hexadecenoic 2) 16:1Δ9 3) ω-7  Nomenclature & Structure Stearic acid: CH3(CH2)16COOH 1) Octadecanoic 2) 18 Δ0 Oleic acid: CH3(CH2)7CH=CH(CH2)7COOH 1) Octadecenoic 2) 18:1Δ9 3) ω-9  Nomenclature & Structure Linoleic:CH3(CH2)4CH=CHCH2CH=CH (CH2)7COOH 1) 9,12-Octadecenoic 2) 18:2Δ9,12 3) ω-6,9 Linolenic:CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH 1) 9,12,15-Octadecenoic 2) 18:3Δ9,12,15 3) ω-3,6,9 Both are essential FAs  Nomenclature & Structure Arachidonic: CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH 1) 20:4Δ5,8,11,14 2) ω-6,9,12,15 It is a semi-essential FA  Derivatives of fatty acids 1. Ketone bodies: They are small, water soluble molecules including acetone, acetoacetate and β-hydroxybutyrate, all of which are formed from fatty acids and carbohydrates 2. Eicosanoids: Prostaglandins (PG) & related compounds (thromboxanes (TX) & leukotrienes (LT), are collectively known as eicosanoids where they originate from Arachidonic acid (polyunsaturated fatty acid with twenty carbons). They have been compared to hormones in terms of their action but they differ from them in: 1- They are produced in small amounts in almost all tissues rather than in specialized glands 2- They act locally rather than after transport in blood to distant sites (such as insulin) 3- They are not stored, and they have an extremely short half-life  Biosynthesis of Prostaglandins With the exception of RBCs, PGs are produced and released by nearly all mammlian cells The immediate precursor of PG is arachidonic acid (20:4) which is derived from: a) Linoleic acid (18:2) present in diet. b) Phospholipids present in cell membrane by the action of phospholipase A2. c) Diacylglycerol by DG lipase The first step in PG synthesis Is the oxidation and cyclization of arachidonic acid to give PGG2, then PGH2 (the precursor for a number of prostaglandins) This is done by cyclooxygenase enzyme (COX)  Two isozymes of COX; COX-1 and COX-2 are known COX-1 is made in most tissues COX-2 is inducible in a limited number of tissues in response to products of activated immune and inflammatory cells. The increase in prostaglandin synthesis subsequent to the induction of COX-2 mediates the pain, heat, redness, swelling of inflammation and the fever of infection Linoleic acid DAG  Inhibition of prostaglandin synthesis It can be inhibited by : 1- Cortisol (a steroidal anti- inflammatory agent) inhibits phospholipase A2 activity 2- Aspirin, indomethacin, and phenylbutazone (all nonsteroidal anti-inflammatory drugs [NSAIDs]) Inhibit both COX-1 and COX2 and, thus, prevent the synthesis of the parent prostaglandin PGH2. Systemic inhibition of COX-1, with subsequent damage to the stomach and the kidneys and impaired clotting of blood, is the basis of aspirin’s toxicity.  Functions of prostaglandins 1) Inflammation Natural mediators of inflammation Anti-inflammatory drugs e.g. Aspirin and Indomethacin inhibit PG synthesis 2) Ensure gastric integrity PGs inhibit gastric acid secretion in patients with peptic ulcers. PGs also accelerate the healing of gastric ulcers 3) Regulation of blood pressure PGE and PGA decrease systemic arterial blood pressure due to vasodilatation 4) Maintain platelet homeostasis PGI2 (Prostacyclin) inhibits platelet aggregation. PGE2 and thromboxan A2 (TXA2) stimulate platelet aggregation  Leukotrienes Leukotrienes are synthesized by lipooxygenase from Arachidonic acid in: ✓ leucocytes ✓ platelets ✓ mast cells ✓ macrophages Leukotrienes are mainly involved in allergic reactions. Lipids  Nature of lipids Lipids are naturally occurring heterogeneous groups of organic compounds. They are water-insoluble (hydrophobic), & soluble in organic solvents (e.g. ether, chloroform and benzene) They are hydrophobic in nature due to the predominance of hydrocarbon chains [-(CH2)n-] in their structures  Importance of lipids Major source of energy for the body Thermal insulator in the subcutaneous tissue and around certain organs Electrical insulators in the myelinated nerves Help in the absorption of fat-soluble vitamins which act as co-enzymes & have regulatory functions in metabolism Lipids are precursors of steroid hormones which have an important role in body homeostasis Structural components of biological membranes Help in the fixation of internal organs Deficiencies or imbalance in lipid metabolism leads to some health problems as obesity, hyperlipidemias & atherosclerosis  Lipids Classification I- Simple Lipids II- Compound Lipids III- Substances associated with lipids  I) Simple lipids R-COOH (fatty acid) + R’-OH (fatty alcohol) R-COOR’ lipid (ester) Monohydric fatty alcohol Waxes (CH3 (CH2)n OH) Glycerol +1FA +2FAs +3FAs Also known as triglycerides (neutral fats) It is the form in which fats are stored in adipose tissue They can be simple: same R, or mixed: different Rs  II) Compound lipids (Lipids + a prosthetic group): ❑ Phospholipids: Lipids + P ❑ Glycolipids: Lipids + Carbohydrates ❑ Sulpholipids: Lipids + S ❑ Lipoproteins: Lipids + Proteins  Phospholipids Phospholipids are present in every body cell Phospholipids are a constituent of cell and mitochondrial membranes There are two classes of phospholipids: I) Glycerophospholipids II) Sphingolipids I) Glycerophospholipids: Most phospholipids are derivatives of glycerol They consist of a glycerol molecule (main backbone) , two fatty acids, and a phosphate group that is attached to an alcohol. The phosphate group is the negatively-charged polar head, which is hydrophilic. The fatty acid chains are the uncharged, nonpolar tails, which are hydrophobic.  Examples of glycerophospholipids Phosphatidic acid: this is the simplest phosphoglyceride, and is the precursor of the other members of this group. The phosphate group on the phosphatidic acid (PA) can be esterified to another compound containing an alcohol group. Phosphatidyl choline (lecithin): The most important of this is the dipalmitoyl lecithin or DPPC. In which, the positions of 1&2 on the glycerol are occupied by palmitate. This is the major lipid component of lung surfactant- the extracellular fluid layer lining the alveoli. They serve to decrease the surface tension preventing alveolar collapse(atelectasis) Respiratory distress syndrome(RDS) in pre-term infants is associated with insufficient DPPC production & is significant cause of all neonatal deaths in western countries.  Lipoproteins They are composed of lipids and proteins They help to transport lipids in blood and play a Composition of lipoproteins role in lipid metabolism hHYsurface Hydrophilic Lipoproteins are classified by their density, which inversely reflects their size Types of lipoproteins: 1- Chylomicrons: formed mainly of exogenous triglycerides (TG) 2- Very low-density lipoproteins (VLDLs): contain Hydrophobic core mainly the hepatic TG carrying endogenous TG from liver to extrahepatic tissues 3- Low-density lipoproteins (LDLs): its main lipid content is cholesterol carrying cholesterol to the tissues 4- High-density lipoproteins (HDLs): Its main lipid content is phospholipid rather than cholesterol. HDLs carry cholesterol from the various tissues to the liver.  III-Substances associated with lipids Substances associated with fat in nature and related to them in properties and metabolism These substances include: ❖ Sterols & steroids ❖ Fat soluble vitamins The most important steroids & sterols Cholesterol (animal origin) Vitamin D group (D2 and D3 ) Bile salts. Steroid hormones: 1) male sex hormones 2) female sex hormone 3) adrenocortical hormones  Sterols & Steroids Cholesterol is the characteristic steroid alcohol of animal tissues Function of Cholesterol: 1- It is a structural component of all cell membranes. 2- It is the precursor of bile acids, steroid hormones & vitamin D 3- Component of plasma lipoprotein Liver regulates cholesterol homeostasis: 1- Sources of cholesterol: a) dietary cholesterol b) de novo synthesis mainly in liver 2- Elimination of Cholesterol from liver: a) In bile b) Converted to bile salts Note: Imbalance between cholesterol influx & efflux result in gradual deposition of cholesterol in the tissues resulting in atherosclerosis & increasing the risk of coronary heart diseases  Structure of Cholesterol: Cholesterol is a very hydrophobic compd. It consists of four fused rings (A,B,C &D) and it has an eight carbon, branched chain attached to C-17 of the D- ring. Ring A has a hydroxyl gp at C-3, and ring B has a double bond between C-5 and C-6. 1) Cholesterol (C): The major cholesterol is animal cholesterol. It is absorbed form the intestinal mucosa. Note: Plant sterols are poorly absorbed by humans and appear to block the absorption of dietary cholesterol (That’s why daily ingestion of plant steroid esters leads to reduction of plasma cholesterol level) 2) Cholesteryl esters (CE): Most plasma cholesterol is in an esterified form (with a fatty acid attached at C-3 which is more hydrophobic than free Cholesterol. Because of their hydrophobicity, C & CE, must be transported in association with protein (lipoprotein particle) or solubilized by phospholipids and bile salts in bile  Bile salts Bile salts are bile acids (cholic acid) conjugated with 1- Glycine 2- Taurine Formation of cholic acid from cholesterol occurs in the liver  Female sex hormones Site of production: Site of production: *Ovary and placenta in females *Ovary and placenta in females *Adrenal cortex in both males and *Adrenal cortex in both males females and females Functions: Functions: It stimulates the growth of female ▪ It prepares the uterus for sex characters and organs implantation of the ovum ▪ It stabilizes pregnancy (it prevents abortion)  Male sex hormone Site of production: *Is produced by the gonads (by the Leydig cells in testes in males and by the ovaries in females) *Adrenal cortex in both males and females Functions: It stimulates the development of male sex characters and organs  Adrenal cortical hormones Glucocorticoids: Mineralocorticoids: ▪ Control the metabolism of Control the metabolism carbohydrates, proteins and fats of Na, K, Cl and water ▪ Suppresses the immune system  FAs & Lipids Classification of FAs Classification of lipids Saturated FAs Essential FAs Substances Unsaturated FAs Non-essential FAs Simple Compound associated lipids lipids Common names with lipids Systemic Naming FAs Δ-System ω–system Monoacylglycerol Diacylglycerol Ketone bodies Triacylglycerol Derivatives of FAs Eicosanoids Prostaglandins Leukotrienes Phospholipids Lipoproteins Cholesterol Bile salts. Steroid hormones