Biochemistry 1 Lec 7 - Fatty Acids & Lipids PDF

## Biochemistry 1 Lec.7: Fatty Acids & Lipids **DR. KD** **Tiba center** ### Fatty acids - **Long-chain hydrocarbon molecules** containing carboxylic acid moiety at one end. - At physiological pH: readily ionized & thus carries a negative charge but still hydrophobic. - **Hydrocarbon chain** - **C...

## Biochemistry 1 Lec.7: Fatty Acids & Lipids **DR. KD** **Tiba center** ### Fatty acids - **Long-chain hydrocarbon molecules** containing carboxylic acid moiety at one end. - At physiological pH: readily ionized & thus carries a negative charge but still hydrophobic. - **Hydrocarbon chain** - **Carboxyl group** ### Classifications of fatty acids #### According to need of the body - **Essential:** cannot be synthesized by the body & must be obtained from the diet (linoleic & linolenic). - **Non-essential:** can be synthesized by the body & non-essential in the diet. #### According to degree of saturation with hydrogen atoms - **Saturated (no double bonds):** all C-C bonds are single. Solid at room temperature. Formula: $CH_3 (CH_2)_n COOH$. - **Mono- or polyunsaturated:** has one or more double bonds. Liquid at room temperature. - **Addition of double bonds decreases melting point**, therefore unsaturation enhances fatty acid fluidity. - **Polyunsaturated fatty acids (linoleic & linolenic) are essential.** - **No human enzymes can introduce a double bond except between ninth carbon & COOH carbon.** (No human enzymes can introduce a double bond after C9) ### Saturated Fatty Acid $H-O - C = \begin{matrix} H \\ H - C - \\ H \end{matrix}\begin{matrix} H \\ H - C - \\ H \end{matrix}\begin{matrix} H \\ H - C - \\ H \end{matrix}\begin{matrix} H \\ H - C - \\ H \end{matrix}\begin{matrix} H \\ H - C - \\ H \end{matrix}\begin{matrix} H \\ H - C - \\ H \end{matrix}\begin{matrix} H \\ H - C - \\ H \end{matrix}\begin{matrix} H \\ H - C - \\ H \end{matrix}\begin{matrix} H \\ H - C - \\ H \end{matrix}\begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} H$ ### Unsaturated Fatty Acid $H - O - \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ C = C \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} \begin{matrix} H \\ H - C - \\ H \end{matrix} H$ ### 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 FAs #### Solubility 1. Lower members: soluble in $H_2O$ 2. Increasing chain: decreases solubility 3. FA more than 10 carbon atoms: insoluble in $H_2O$ & soluble in fat solvents. #### Melting points 1. Saturated FA: high melting point, solids at room temperature. 2. Unsaturated FA: have low melting point, liquids (oils) at room temperature. #### Cis and trans isomerism - The presence of a double bond in FA gives rise to cis-trans isomerism. - **Cis double bond:** same side, healthy. - Nearly all naturally occurring oils FA have a double bond in cis configuration. - **Trans double bond:** opposite sides, unhealthy. - FAs behave more like saturated FAs. - Elevate serum LDL & increase risk of coronary heart disease. - Not present in plants. ### FAs nomenclature - **FA carbon atoms are numbered starting at COOH terminus:** - **C1:** C of COOH - **C2:** u C (Alpha) - **C3:** B C (Beta) - **C4:** y C (Gama) - The methyl carbon atom at the distal end ($CH_3$ terminus) of chain is called w C (Omega) #### Ways of Naming of FA 1. **Common Name:** name by which the FA is known. 2. **Systemic Name:** no of carbons + changing suffix e with oic. - C18 saturated FA: octadecanoic - C18 with double bond FA: octadecenoic. #### A-System (Delta) - **1st no. before A:** no of carbons in chain. - **2nd no. before A:** no of double bonds in chain. - **No. after A:** position of double bonds. - 18: C18 FA with no double bonds, saturated. - 18:1A: C18 fatty acid with one double bond at C9 - Cis 18:1A: C18 with cis double bond between C9 & 10 - Trans 18:2 19,12: C18 with two trans double bonds at C9 & C12. #### w-system (Omega) - **Denoting position of 1st double bond from the CH3 terminus side of chain.** - Carbon of terminal methyl group: w C - w-3 FA: double bond at C3 from methyl terminus. - w-6 FA: double bond at C6 from methyl terminus. ### Palmitic Acid [16C] [Saturated] - Formula: $CH_3CH_2CH_2(CH_2)_9CH_2CH_2CH_2COOH$ ### Palmitoleic Acid [16C] [1 double bond] - Formula: $CH_3(CH_2)_5CH=CH(CH_2)_7COOH$ ### Stearic Acid [18C] [Saturated] - Formula: $CH_3(CH_2)_{16}COOH$ ### Oleic Acid [18C] [1 double bond] - Formula: $CH_3(CH_2)_7CH=CH(CH_2)_7COOH$ ### Linoleic [18C] [2 double bonds] [Essential FA] - Formula: $CH_3(CH_2)_4CH=CHCH_2CH=CH(CH_2)_7COOH$ ### Linolenic [18C][3 double bonds] [Essential FA] - Formula: $CH_3CH_2CH=CHCH_2CH=CHCH_2CH=CH(CH_2)_7COOH$ ### Arachidonic [20C] [ 4 double bonds] [Semi-essential FA] - Formula: $CH_3(CH_2)_4CH=CHCH_2CH=CHCH_2CH=CHCH_2CH=CH(CH_2)_3COOH$ ### Derivatives of fatty acids #### Ketone bodies - Small, water-soluble molecules including: acetone, acetoacetate & B-hydroxybutyrate. - All are formed from fatty acids & carbohydrates. #### Eicosanoids - Prostaglandins (PG) & related compounds (Thromboxanes (TX) & Leukotrienes (LT)) - Known as eicosanoids. - Originate from Arachidonic acid (polyunsaturated fatty acid with 20C). - Very important (exam) ##### Eicosanoids 1. Produced in small amounts in almost all tissues. 2. Act locally. 3. Not stored, extremely short half-life. ##### Hormones 1. Produced in specialized glands. 2. Transported in blood to distant sites. 3. Stored, long half-life. #### Biosynthesis of Prostaglandins - PGs produced & released by nearly all mammalian cells (except RBCs). - **Arachidonic acid:** the immediate precursor of PG. Derived from: 1. Linoleic acid (18:2): present in diet 2. Phospholipids: present in cell membrane by action of phospholipase A2 3. Diacylglycerol (DG): by action of DG lipase. - Arachidonic acid is semi-essential. - **1st step:** oxidation & cyclization by COX Enz. $PGG_2 \rightarrow PGH_2$ - **Cyclooxygenase enzyme (COX) has two isoenzymes: COX-1 & COX-2** #### Inhibition of prostaglandin synthesis - **Phospholipids in cell membrane:** phospholipase - **Cortisol:** corticosteroid - **Cyclooxygenase:** ($NSAID$): ASA - **Lipoxygenas e:** leukotrienes (LTB/C/D/E) - **Prostaglandins:** $PGF_2$/$PGI_2$/$PGD_2$/$PGE_2$/$TxA_2$ 1. **Cortisol (steroidal anti-inflammatory agent):** inhibits phospholipase A2, and avoids arachidonic. 2. **Aspirin, indomethacin, & phenylbutazone (nonsteroidal anti-inflammatory drugs [NSAIDs]):** format. - Inhibit both COX-1 & COX-2: prevent synthesis of parent PG ($PGH_2$). - Systemic inhibition of COX-1: subsequent damage to stomach & kidneys & impaired blood clotting. - The basis of aspirin’s toxicity. ### Functions of prostaglandins 1. **Inflammation:** - Natural mediators of inflammation. - Anti-inflammatory drugs (e.g. Aspirin & Indomethacin) inhibit PG synthesis. 2. **Ensure gastric integrity:** - PGs inhibit gastric acid secretion in patients with peptic ulcers. - PGs also accelerate healing of gastric ulcers. 3. **Regulation of blood pressure:** - PGE & PGA decrease systemic arterial blood pressure due to vasodilatation. 4. **Maintain platelet homeostasis:** - PGI2 (prostacyclin) inhibits platelet aggregation. - PGE2 & Thromboxane A2 (TXA2) stimulate platelet aggregation. ### Leukotrienes - **Arachidonic acid** - **Lipoxygenase enzyme [LOX]** - **Leukotrienes (LT)** - Synthesized in: - Leukocytes - Platelets - Mast cells - Macrophages - Leukotrienes are mainly involved in chemotaxis & allergic reactions. ### Lipids - **Naturally occurring heterogeneous groups of organic compounds.** - **Water-insoluble & soluble in organic solvents (ether, chloroform & benzene).** - **Hydrophobic in nature due to the predominance of hydrocarbon chains [-(CH2)n-] in their structures.** #### Importance of lipids 1. **Major source of energy for the body.** 2. **Thermal insulator in subcutaneous tissue & around certain organs.** 3. **Electrical insulators in myelinated nerves.** 4. **Help in the absorption of fat-soluble vitamins which act as co-enzymes & have regulatory functions in metabolism.** 5. **Lipids are precursors of steroid hormones which have an important role in body homeostasis.** 6. **Structural components of biological membranes.** 7. **Help in the fixation of internal organs.** 8. **Deficiencies or imbalance in lipid metabolism lead to some health problems as obesity, hyperlipidemias & atherosclerosis.** #### Lipids Classification - **Simple Lipids** - **Compound Lipids** - **Substances associated with lipids** ##### Simple lipids [FA + Alcohol = Ester] - R-COOH (fatty acid) + R'-OH (fatty alcohol) ###### Monohydric fatty alcohol - (CH3(CH2)n OH) ###### Glycerol - **Monoacylgycerol** - **Diacylglycerol** - **Triacylglycerol** - Also known as **triglycerides (neutral fats)** - The form in which fats are stored in adipose tissue - May be **simple:** same R, or **mixed:** different R. ##### Compound lipids [Lipid + Prosthetic group] - **Phospholipids:** lipids + P - **Glycolipids:** lipids + carbohydrates - **Sulfolipids:** Lipids + S - **Lipoproteins:** lipids + proteins ###### Phospholipids - Present in every body cell. - Constituent of cell & mitochondrial membranes. - Two classes of phospholipids: - **Glycerophospholipids:** Most phospholipids are derivatives of glycerol. - **Sphingolipids:** ####### Glycerophospholipids - 1 glycerol molecule (main backbone) + 2 FA + P attached to alcohol. - Phosphate group: negatively charged, polar head, hydrophilic. - Fatty acid chains: uncharged, nonpolar tails, hydrophobic. ###### Phosphatidic Acid (PA) - The simplest phosphoglyceride. - Precursor of other members of this group. - The P on phosphatidic acid (PA) can be esterified to another compound containing an alcohol group. ###### Phosphatidyl Choline (Lecithin) - Dipalmitoyl lecithin or DPPC: 1 & 2 on glycerol occupied by palmitic. - Major lipid component of lung surfactant: the extracellular fluid layering lining alveoli. - Decrease surface tension: preventing alveolar collapse (atelectasis). - Respiratory distress syndrome (RDS) in pre-term infants is associated with insufficient DPPC production, a significant cause of all neonatal deaths in western countries. ###### Sphingolipids - Hydrophobic tails #### Substances associated with lipids - Substances associated with fat in nature & related to them in properties & metabolism, including: - 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. ### Cholesterol - Characteristic steroid alcohol of animal tissues. #### Function of Cholesterol 1. Structural component of all cell membranes. 2. Precursor of bile acids, steroid hormones & vitamin D. 3. Component of plasma lipoprotein. #### Liver regulates cholesterol homeostasis 1. **Sources of cholesterol:** - Dietary cholesterol - De novo synthesis mainly in liver. 2. **Elimination of Cholesterol from liver:** - In bile - Converted to bile salts. #### Imbalance between cholesterol influx & efflux - Results in gradual deposition of cholesterol in tissues, resulting in atherosclerosis & increasing risk of coronary heart diseases #### Structure of cholesterol - Very hydrophobic compound. - 4 fused rings: A, B, C & D - C-17 of D ring: 8C branched chain. - C-3 of A ring: OH gp. - B ring: 1 dB between C-5 & C-6. #### Cholesterol - Major cholesterol is animal cholesterol. - Absorbed form intestinal mucosa. - Daily ingestion of plant steroid esters leads to reduction of plasma cholesterol level (G.R). - Plant sterols are poorly absorbed by humans & appear to block absorption of dietary cholesterol. #### Cholesteryl esters (CE) - Most plasma cholesterol is in an esterified form. - FA 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 & bile salts in bile. ### Derivatives of cholesterol - **Bile Salts:** (salt of bile acids). - Bile acids (cholic acid) conjugated with: - Glycine: glycocholic acid. - Taurine: Taurocholic acid. - **Formation of cholic acid from cholesterol occurs in liver.** #### Female sex hormones - **Estradiol:** - Site of production: - Ovary and placenta in females - Adrenal cortex in both males and females - Functions: - It stimulates the growth of female sex characters and organs #### Male sex hormones - **Testosterone:** - 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 #### Progesterone - Site of production: - Ovary and placenta in females - Adrenal cortex in both males and females - Functions: - It prepares the uterus for implantation of the ovum - It stabilizes pregnancy (it prevents abortion) ### Adrenal cortical hormones #### Glucocorticoids - Control the metabolism of carbohydrates, proteins and fats. - Suppresses the immune system. - **Cortisol:** #### Mineralocorticoids - Control the metabolism of Na, K, Cl and water. - **Aldosterone:** ### Classification of FAs - **Saturated FAs:** - Essential FAs - Non-essential FAs - **Unsaturated FAs:** - Common names - Systemic - A-System - w-system - Derivatives of FAs: - Ketone bodies - Eicosanoids - Prostaglandins - Leukotrienes ### Classification of Lipids - **Simple lipids:** - Monacylglycerol - Diacylglycerol - Triacylglycerol - **Compound lipids:** - **Substances associated with lipids:** - Cholesterol - Bile salts. - Steroid hormones