Lec 1 Lipid Met Under 18.9.2024 PDF

Lipid Metabolism Fatty acids properties 18.9.2024 Lipids are a heterogeneous group of substances that are insoluble in water but soluble in organic solvents. They are sometimes defined as substances that are related directly or potentially to fatt...

Lipid Metabolism Fatty acids properties 18.9.2024 Lipids are a heterogeneous group of substances that are insoluble in water but soluble in organic solvents. They are sometimes defined as substances that are related directly or potentially to fatty acids. Properties of fatty acids: - Free or esterified: Fatty acids (F.As) are mostly present as esterified F.As such as in triacylglycerols (TAGs) of adipose tissues. Some F.As are found in the body as free and called non-esterified fatty acids (NEFA) or free fatty acids (FFAs). Under usual conditions, FFAs do occur in low levels in all tissues but substantial amounts can be found in plasma during fasting or starvation. - Short or long: Fatty acids are mostly long in the body. Long chain F.As, even when are free, they are highly hydrophobic, then are really carried in plasma by albumin and, in cell cytoplasm by special proteins. Short chain fatty acids can be really free. - Even-numbered or odd-numbered F.As: In natural fats, most F.As contain an even- number of carbon atoms because they are synthesized from two carbon units (ie, acetyl CoA). - Straight chain or branched chain F.As: FAs are usually straight chain. However, branched chain fatty acids do occur in nature. For example, phytanic acid is present in significant amounts in dairy products and is coming from plants ingested by cattle. Phytanic acid 1 - Saturated or unsaturated: Saturated fatty acids contain no double bonds while unsaturated F.As contain either one double bond (monounsaturated) or two or more double bonds (polyunsaturated). - The melting point of a F.A: It depends on two factors: a. increases or being higher with the increase in chain lenghth ( longer F.As are solid) b. decreases according to unsaturation (unsaturated F.As are more liquid) Example: Triacylglycerols containing all saturated F.As of C12 or more are solid at body temperature, whereas if all 3 fatty acid residues are 18:2, a triacylglycerol is liquid to below 0 Cº. Functionally, membrane lipids are more unsaturated than storage lipids. - Cis or trans isomer: Most naturally occurring unsaturated F.As have ( Cis ) double bonds ,i. e, the acyl chains are on the same side of the bond and the molecule is being bent 120 degrees at the double bond (see the figure). 2 Nomenclature of fatty acids All - cis - 5,8,11,14- Eicosatetraenoic acid 3 Nutritionally essential fatty acids Linoleic and linolenic acids can not be synthesized in the body and must be supplied in the diet and so are known as essential for the complete nutrition of many species of animals including humans. Arachidonic acid also can not be synthesized but can be derived from linoleic acid when it is missing in the diet and linoleic is available (so arachidonic acid is called semi-essential). Essential fatty acids (EFA) are important because: - are components of phospholipids and - are required for fluidity of membrane structure and - are required for synthesis of eicosanoids. A deficiency of EFA will lead to: - scaly dermatitis - hair loss and - poor wound healing. Because EFAs are widely distributed in nature, therefore a deficiency is rare. However, if a patient is only on synthetic diets such as that used in parenteral nutrition then the given diet should include about 2% of calories as linoleic acid. 4  Tiacylglycerols Triacylglycerols (TAGs) are esters of the alcohol glycerol and fatty acids: In naturally occurring fats, few TAGs molecules have the same F.As in all positions represented by R1, R2, and R3. Example: if R1, R2, R3 all are stearic acid then such TAG is named tristearin. Most TAGs are mixed acylglycerols, R1 is usually saturated, R2 is commonly unsaturated and R3 can be either. Example: the Palmito-oleio – stearin. Storage of triacylglycerols: Because TGs are only slightly soluble in water, they coalesce within adipocytes to form oily droplets that are nearly anhydrous. These lipid droplets are the major energy reserve of the body. Synthesis of triacylglycerols Synthesis of TAGs requires activation of fatty acids as well as activation of glycerol. Activation of a free fatty acid: A fatty acid must be converted into its activated form (by attachment to coenzyme A) before it can participate in TAGs synthesis. This reaction is catalyzed by thiokinase (acyl CoA synthetase or acyl CoA ligase). 5  Thiokinase (Acyl CoA synthetase) Activation of glycerol: Glycerol is activated through attachment to phosphate. There are two pathways for glycerol phosphate production: In both, the liver (the primary site of TAGs synthesis) and adipose tissues, glycerol phosphate can be produced from glucose by utilizing glycerone phosphate (dihydroxyacetone phosphate ; DHAP) which is produced in the glycolytic pathway. DHAP undergoes reduction by glycerol phosphate dehydrogenase to glycerol phosphate. A second pathway that is present in the liver but Not in adipose tissues converts free glycerol to glycerol phosphate by the enzyme glycerol kinase, an enzyme that is weak or absent in adipose tissue. Clinical correlation: Adipocytes can take up glucose only in the presence of the hormone insulin. Thus, when plasma glucose is low such as in fasting and insulin level is low and no glucose enters adipocytes then adipocytes have only a limited ability to synthesize glycerol phosphate and can not produce TAGs. In diabetes mellitus, no glucose enters adipocytes in spite of hyperglycemia because insulin is inactive or low in level and again no TAGs are produced. 6  Activation of glycerol Steps of synthesis of a TAG molecule: Synthesis of a molecule of TAG from glycerol phosphate and fatty acyl CoA: The pathway involves four reactions that include sequential addition of F.As (as fatty acyl CoAs), the removal of phosphate, and an addition of a third fatty acyl. 7 Depot fat: This type of fat appears as yellow white droplets in the cytoplasm of adipose tissue cells (adipocytes). Sites: 1- Under the skin. 2- Around important organs e.g: Kidney. 3- In the omentum and mesentry. Composition: Adipose tissues are composed mainly of TAGs with a little of phospholipids (PLs) and cholesterol. Sources: 1- Absorbed fat. 2- Carbohydrates by lipogenesis. 8