Medical chemistry (2) Part II (Lipids) week 4 lectures “Important reactions of lipids” Taif University College of Medicine Preparatory Year Students

Lectures outlines Definition and importance of lipids Classification of lipids Fatty acids structure and properties Important reactions of FA Glycerides Non-glyceride lipids Membranes Lipids

List the Important reactions of FA? Esterification Hydrolysis of esters Hydrogenation Oxidation and Rancidity Effect of radiation

Esterification

H + / Heat Fatty acids +Alcohol Ester+Water Esterification

Hydrolysis of esters Acid hydrolysis Base hydrolyses (Saponification)

H + / Heat Acid+Alcohol Ester Acid Hydrolysis

Hydrolysis of triglycerides TG In hydrolysis, Triacylglycerols (TAG) split into glycerol and three fatty acids Acid or enzyme catalyst is required

OH - Salt of the acid or soap + Alcohol Ester Base Hydrolysis Saponification Soap

Saponification of TG and Soap Saponification is the reaction of a fat with a strong base splits triacylglycerols into glycerol and the salts of fatty acids is the process of forming “soaps” (salts of fatty acids) with KOH gives softer soaps

Hydrolysis of Triglycerides Enzymatic or Acid Hydrolysis Alkaline Hydrolysis Glycerol Saponification Lipase Glycerol

Learning Check What products are obtained from the complete hydrolysis of glyceryl trioleate? A. glycerol and three oleic acids B. glyceryl tristearate C. glycerol and three stearic acids

Hydrogenation

When hydrogen adds to all the double bonds of glyceryl trioleate (triolein) using a nickel catalyst, the product is the saturated fat glyceryl tristearate (tristearin).

Learning Check What products are obtained from the complete hydrogenation of glyceryl trioleate? A. glycerol and three oleic acids B. glyceryltristearate C. glycerol and three stearic acids

Hydrogenation of Unsaturated Fats X ? Carcinogenic

Learning Check Which of the following statements are true and which are false? A. There are more unsaturated fats in vegetable oils. B. Vegetable oils have higher melting points than fats. C. Hydrogenation of oils converts some cis double bonds to trans double bonds. D. Animal fats have more saturated fats.

Summary of Organic and Lipid Reactions

Oxidation

The carbon–carbon double bonds present in the fatty acid residues of a triacylglycerol are subject to oxidation with molecular oxygen (from air) as the oxidizing agent. Such oxidation breaks the carbon–carbon bonds, producing both aldehyde and carboxylic acid products

Oxidation  The short-chain aldehydes and carboxylic acids often have unpleasant odors and flavors. Fats and oils containing them are said to have become rancid. Rancidity is due to a combination of two reactions:  Bacterial hydrolysis of ester bonds.  Air oxidation of alkene double bonds.

Autoxidation Polyunsaturated Fatty Acids Free Radical Initiation H-abstraction Diene Conjugation O 2 uptake Lipid Peroxides Catalysts (Fe, Fe-O 2 ) Decomposition Rancid off-flavor compounds such as ketones,alcohols, hydrocarbons, acids, epoxides Polymerization ( dark color, possibly toxic )

Rancidity In fats containing triacylglycerols with some low- molecular-mass carboxylic acids, hydrolysis by airborne bacteria under moist, warm conditions is directly responsible for rancid odors and flavors.  To avoid this unwanted oxidation process, commercially prepared foods always contain antioxidants—substances that are more easily oxidized than the food:  vitamins C vitamin E (naturally occurring antioxidants).  BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) (synthetic oxidation inhibitors).

Consequences of Lipid Peroxidation Structural changes in membranes – Alter fluidity and ion channels – Alter membrane-bound signaling proteins – Increase membrane permeability Form lipid oxidation products adducts/crosslinks with non lipids – e.g., proteins and DNA Cause direct toxicity – e.g., 4-hydroxynonenal, Malondialdehyde “MDA” DNA damage and mutagenesis

Antioxidant Defenses in Biological Systems Fat-soluble cellular membrane consists – Vitamin E – beta-carotene – Coenzyme Q (10) Water soluble antioxidant scavengers – Vitamin C – Glutathione peroxidase, – Superoxide dismutase – Catalase

Effect of radiation

Changing the configuration of the double bond cis biradical cis biradical trans

Lipids Classification

Neutral- Glycerides Phospho- Glycerides

Neutral Glycerides

Esters of Fatty acids with Glycerol Neutral glycerides Glycerides

HO 3 H 2 O Ester Bond Esterification glyceride Triglyceride

The simple triacylglycerol produced from the triple esterification reaction between glycerol and three molecules of stearic acid (18:0 acid). Three molecules of water are a by-product of this reaction. Structure of the simple triacylglycerol

Three different fatty acid residues are present Structure of a mixed triacylglycerol

Triglycerides Simple Mixed Triglycerides (TG) Tristearin Stearo, Stearo, Palmitin Palmito, Oleo, Stearin Di-acid Tri-acid

Question Draw the structural formula of the triacylglycerol (TAG) produced from the reaction between glycerol and three molecules of oleic acid?