AIU Medical Biochemistry 2024-2025 Lecture Notes (PDF)

Medical Biochemistry 2024-2025 MACRONUTRIENTS (LIPIDS 2) I. SIMPLE LIPIDS True fats (Neutral fats) These are esters of glycerol and fatty acids. If all the three hydroxyl groups of...

Medical Biochemistry 2024-2025 MACRONUTRIENTS (LIPIDS 2) I. SIMPLE LIPIDS True fats (Neutral fats) These are esters of glycerol and fatty acids. If all the three hydroxyl groups of glycerol are esterified, fats are known as triacylglycerol. The 3 fatty acids linked to glycerol are usually different. Triacylglycerols may be 1. Simple triacylglycerols: i.e. contain a single kind of fatty acid in all the three ester positions. e.g. Tristearin, Tripalmitin and Triolein. 2. Mixed triacylglycerols: i.e. contain 2 or more different fatty acids in the molecule 1  Medical Biochemistry 2024-2025 BIOLOGICAL IMPORTANCE OF TRUE FATS: 1. They form reserve foods in animals, they are found as depot fat in the subcutaneous tissues. This depot fat is mobilized during fasting to produce energy and so its amount is variable, and thus true fats are known as variable element of fat. 2. They are the most compact form in which energy can be stored. (1 gm of fat → 9.3 KCal). 3. True fats are also found as supporting material in some parts of the body as around the kidneys. II- COMPLEX LIPIDS 1. PHOSPHOLIPIDS They are membrane components, amphipathic, ionic compounds. There are two classes of phospholipids: A. GLYCEROPHOSPHLIPIDS, they have glycerol as a backbone B. SPHINGOPHOSPHOLIPIDS. They have sphingosine as a backbone Both are considered as constant element of fat. A. Glycerophospholipids: The precursor compound of glycerophospholipids is L-glycerol-3-phosphate. 2  Medical Biochemistry 2024-2025 The fatty acids present in phosphoglycerides are mostly a saturated FA in the 1st position of glycerol, and anunsaturated FA in the second position. Both are high fatty acids. Phospholipids are considered (amphipathic) because part of the molecule is hydrophilic and polar (phosphoric acid and bases), in addition to their nonpolar hydrophobic hydrocarbon tail. (fatty acids) 3  Medical Biochemistry 2024-2025 Examples of Glycerophospholipids: 1. Phosphatidic acid: is the simplest form. It has no base. It is the precursor of the other members of this group. It is present mainly as an intermediate compound during the synthesis of other Glycerophospholipids and triacylglycerol. 2. Lecithin (phosphatidyl choline): The base is choline. It is present in the animal’s cell membrane. Dipalmitoyl lecithin: in this phospholipid position 1,2 of glycerol are occupied by palmitate. This phospholipid is the major lipid components of lung surfactants. Surfactants serve to decrease surface tension of the fluid layer lining the alveoli; therefore, prevent alveolar collapse. Its absence from the lungs of premature infants causes respiratory distress syndrome (RDS). 4  Medical Biochemistry 2024-2025 3. Lipositol (phosphatidyl inositol): The polar head here is the cyclic hexose sugar alcohol inositol (myoinositol). An important constituent of cell membrane of brain cells and muscles A precursor of second messengers (signaling pathway). 5  Medical Biochemistry 2024-2025 4. Cardiolipin: Is composed of 2 molecules of phosphatidic acid linked together covalently through a molecule of glycerol. It occurs in the inner membrane of the mitochondria of metabolically active tissues e.g. heart muscle. Amphipathic lipids. Compounds which contain both polar and nonpolar groups. The phosphoryl bases are considered as polar, hydrophilic, heads (ionizable heads) present in phosphoglyceride) in addition to their hydrocarbon hydrophobic tails (nonpolar tails). So they are arranged in the cell membrane as bilayer. In such structures, the hydrocarbon tails are hidden from the aqueous medium whereas the hydrophilic polar heads are exposed on the surface. 6  Medical Biochemistry 2024-2025 Phospholipids form the bilayer Phospholipids form micelles and Liposomes 7  Medical Biochemistry 2024-2025 B. Sphingophospholipids This group of phospholipids contain sphingosine instead of glycerol, a longer chain fatty acid as lignoceric acid, phosphoric acid and a base. They are important membrane components both in plants and animal cells. They are present especially in large amounts in brain and myelin of nerve tissues. The combination of sphingosine fatty acid is known as CERAMIDE. Ceramide is the parent structure of all sphingolipids. The most abundant sphingophospholipids in tissues of animals are sphingomyelins. They contain a phosphoryl choline as their polar head group. 2- GLYCOLIPIDS (GLYCOSPHINGOLIPIDS) Glycolipids are widely distributed in every tissue of the body, particularly in nervous tissue such as brain. They occur also in the outer leaflet of the plasma membrane having a role in cell communication. 8  Medical Biochemistry 2024-2025 III.DERIVED LIPIDS From hydrolysis of simple and complex lipids They include: 1. Fatty acids. 2. Glycerol. 3. Alcohols (other than glycerol). 4. Steroids. 5. Carotenoids. 6. Fat Soluble vitamins. They are either derived from simple and compound lipids (1,2,3) or associated with lipids (4,5,6), and they possess the general physical characteristics of lipids. 9  Medical Biochemistry 2024-2025 Steroids Steroids are any compound having steroid nucleus: In this structure, a simple hexagonal ring denotes a completely saturated 6 carbon ring, ie, it is not a benzene ring. There is methyl group at C10 (it makes C19). There is methyl group at C13 (it makes C18). So, this ring is composed of 17 carbon atoms besides two methyl groups (C18, C19). Steroids include: A. Sterols B. Bile acids and salts C. Steroid hormones D. Vitamin D 10  Medical Biochemistry 2024-2025 A) STEROLS: This group of steroids has a hydroxyl group (OH) at C3 i.e. it is an alcohol, and an aliphatic side chain at C17. Types of sterols: 1. Animal sterols: Cholesterol & its derivative 7-dehydrocholesterol. 2. Plant sterols: Ergosterol and 22-dihydroergosterol. Cholesterol: Biomedical importance: 1- Main sterol in human body. 2-It is a major constituent of the plasma membrane. 3-Precursor of sex hormones, cortical hormones, vitamin D and bile acids. 11  Medical Biochemistry 2024-2025 Sources: 1- It is formed in the body from acetyl CoA. 2- It is present in diet: egg yolk, meat, liver and brain. (It occurs in animal fats but not in plant fats). ▪ It is present in blood (normal level 150-200 mg / dl). ▪ High level of cholesterol in blood will lead to “atherosclerosis”. ▪ Also high levels of blood cholesterol may lead to stones in gall bladder (gall stone). Cholesterol derivative: 7-dehydrocholesterol (Provitamin D3) 7-dehydrocholesterol is stored under the skin, and by the effect of ultraviolet rays (in sunlight) it is transformed to cholecalciferol ( vit. D3.) 12  Medical Biochemistry 2024-2025 B) BILE ACIDS: They are obtained in the liver by oxidation of cholesterol at C24 with removal of the last 3 carbon atoms. They are the end products of cholesterol catabolism in the body because the body can not break down the steroid nucleus. Types of bile acids: I. Primary bile acids: Cholic acids: (glycocholic and taurocholic are primary bile acids). II. Secondary bile acids: They are produced by action of intestinal bacteria on 1ry bile acids. (deconjugation from glycine or taurine and 7- dehydroxylation). Deoxycholic acid (from cholic acid) ** Bile Salts: They are the products of conjugation of primary bile acids with glycine or taurine mainly in their sodium or potassium salts. 1. Sodium or potassium glycocholate. 2. Sodium or potassium taurocholate. 13  Medical Biochemistry 2024-2025 BILE ACIDS AND SALTS  Help in lipid digestion and absorption and absorption of fat soluble vitamins  Bile salts secreted into the intestine are efficiently reabsorbed and reused ***Cholestyramine: Bile acid sequestrants, such as cholestyramine, bind bile acids in the gut, prevent their reabsorption and so promote their excretion. They are used in the treatment of hypercholesterolemia because the removal of bile acids relieves the inhibition on bile acid synthesis in the liver, thereby diverting additional cholesterol into that pathway. ❖ Note: Dietary fiber also binds bile acids and increases their excretion. 14