BIOC201_Lipids Chemistry [Series 2].pdf

BIOC201W1 INTRODUCTION TO BIOMOLECULES LIPID CHEMISTRY GLYCERIDES 2. Neutral esters of fatty acids and glycerol - GLYCERIDES Ester of fatty acids and tri-hydric alcohols (glycerol) where they form this neutral lipids by esterification reaction...

BIOC201W1 INTRODUCTION TO BIOMOLECULES LIPID CHEMISTRY GLYCERIDES 2. Neutral esters of fatty acids and glycerol - GLYCERIDES Ester of fatty acids and tri-hydric alcohols (glycerol) where they form this neutral lipids by esterification reaction Page 13 in Handouts  GLYCERIDES Nomenclature oThe product can be named as acylglycerol or glyceride such as monoacylglycerol or monoglyceride oMono-, di- and tri- are used based on the number of fatty acids are esterified with the tri- hydric alcohol oNumber of carbons, where fatty acid molecules are added into the tri-hydric alcohol, are also used before the name of these lipids such as 1-Monoacylglycerol, 2-Monoacyl glycerol, 1,3-Diacylglycerol etc. Page 13 in Handouts GLYCERIDES Based on the number of fatty acids esterified with the tri hydric alcohol, neutral lipids are classified into three classes: i) Monoacylglycerol or Monoglyceride ii) Diacylglycerol or Diglyceride iii) Triacylglycerol or Triglyceride Page 13 in Handouts  CLASSIFICATION OF GLYCERIDES i) Monoacylglycerol or monoglyceride (MG): When only one fatty acid molecule esterified with the anyone of the carbons of tri-hydric alcohol is called monoacylglycerol or monoglyceride such as 1, 2, or 3-Monoacylglycerol or 1,2, or 3-Monoglyceride The hydroxyl (-OH) groups present in the carbon number 1, 2 and 3 are called primary, secondary and tertiary hydroxyl groups and their respective carbons are called α, β, and γ carbon So, if a fatty acid molecule esterified with the carbon-1, 2 or 3 that is also called α, β, or γ-monoglyceride respectively ii) Diacylglycerol (DAG) or diglyceride (DG) When two fatty acid molecules are esterified with any two carbons of tri-hydric alcohol is called diacylglycerol or diglyceride such as 1,3-diacylglycerol or 1,3-diglyceride Two fatty acid molecules may or may not be the same Page 13 in Handouts  CLASSIFICATION OF GLYCERIDES iii) Triacylglycerol (TAG) or triglyceride (TG) When three different or same fatty acid molecules are esterified with a tri-hydric alcohol that is called triacylglycerol or triglyceride This is the most widely available neutral lipid in the animal system (95% of the total lipid in our body) Animal fats are mostly consist of esters of palmitic, stearic, palmitoleic and oleic acids with glycerol Page 13 in Handouts PHOSPHOLIPIDS 3. Ionic esters of fatty acids and glycerol Phospholipids are the ionic esters of: glycerol  fatty acid  phosphoric acid and  a base They have a polar head and a non-polar part in their structure so they are AMPHIPATHIC in nature Page 14 in Handouts PHOSPHOLIPIDS Generally saturated fatty acids esterified with carbon 1 & 2 and unsaturated fatty acids with carbon 2 of glycerol molecule Phosphoric acid binds with the hydroxyl group of carbon 3 and a base is linked with the phosphoric acid molecule Page 14 in Handouts  PHOSPHOLIPIDS 1. Lecithin also called phosphatidylcholine Although triglycerides are most abundant lipids in animals and plants but they are not found in biological membranes. Lecithin is the most abundant lipids in biological membranes and lipoproteins of animals and plants. The name and function of the phospholipids are different mainly based on the types of the base. Page 14 in Handouts PHOSPHOLIPIDS 2. Cephalin also called phosphatidylethanolamine Less abundant than Lecithins in the biological system Present mainly in the central nervous system e.g. white matter of brain, spinal cord, neural tissues and nerves. Whereas lecithin is the principal phospholipid in animals, cephalin is the principal one in bacteria. Contains an ethanolamine base in their structure Page 14 in Handouts  PHOSPHOLIPIDS 3. Phosphatidylserine Originally isolated from the bovine brain but nowadays isolating from soybean although they are not exactly the same Present in the inner side of the cell membrane and beneficial to quickly recover from sports or exercise-related injury Contains a serine amino acid as a base in their structure Page 15 in Handouts PHOSPHOLIPIDS 4. Lipositols also called phosphatidylinositol Widely distributed in brain tissue, bacteria and soybean oil Present in the inner side of cell membrane Phosphorylated forms of phosphatidylinositol are called phosphoinositides and play important roles in lipid signaling, cell signaling and membrane trafficking. Contains a myo-inositol (a sugar alcohol) as a base so it is called phosphatidyl inositol Page 15 in Handouts  PHOSPHOLIPIDS 5. Plasmalogens Present in the brain and heart tissues and in low concentration in non-animal tissues This is an exceptional phospholipids The fatty acid chain in the carbon 1 of glycerol is replaced by an α, β-unsaturated ether It may contain choline, ethanolamine or serine as its base Page 15 in Handouts  SPHINGOLIPIDS 4. Lipids without glycerol These lipids are also the major membrane components Most sphingolipids are the derivatives of C18 amino alcohols or sphingosine, whose double bond has the trans configuration N-Acetyl derivatives of sphingosine are known as CERAMIDE These kinds of lipids are mainly composed of:  A long chain fatty acid  A long-chain amino alcohols such as – sphingosine or one of its derivative and  A polar head group of a phosphate and a base Page 16 in Handouts SPHINGOLIPIDS It is a phosphorylcholine derivative of ceramide, accounting for up to 25% of total lipid in human myelin Mainly located in the nerve tissues but also found in blood (lipo-proteins) They are abundant in the myelin sheath, a protective multilayer for insulation of cells of central nervous system Also located in the nerve of the spinal cord Page 16 in Handouts  SPHINGOLIPIDS - SPHINGOMYELIN The fatty acid and long-chain amino alcohol (sphingosine) together constitute a CERAMIDE Finally, a polar head group of phosphate and choline is connected to the fatty acid part of ceramide to form sphingomyelin Page 16 in Handouts  CLINICAL CORRELATION – MULTIPLE SCLEROSIS oAn auto immune disease when immune system attacks the central nervous system and leading to plaques and lesions formation in the myelin sheath followed by demyelination oPrevalent in young adults and more common in females oThe rate prevalence of this disease is 2-150 / 100 000 persons Symptoms: Involuntary movements of eye balls, Fatigue, depression, cognitive impairment, unstable mood Lack of co-ordination, speech and vision problem, Muscular weakness, pains, loss of sensation Abdominal discomfort, diarrhoea, constipation, Irregular frequency of urination Page 16 in Handouts MULTIPLE SCLEROSIS Diagnosis Plaques or lesions in the white matter of the central nervous system and spinal cord can be detected by Magnetic Resonance Imaging (MRI) Treatments No specific treatment is available Several countries started to treat with various immune suppressors such Interferon Beta 1a (IFNβ-1a) and IFNβ-1b Page 16 in Handouts CLINICAL CORRELATION – NIEMANN PICK DISEASE Sphingomyelins are hydrolyzed by an enzyme named sphingomyelinase to from a ceramide and phosphorylcholine Due to the inherited absence of this enzyme unused or extra lipids are deposited in our body what is called Niemann Pick Disease Lipid-laden cells (Foam cells) store in the lung, liver, bone marrow and brain which cause the enlargement of those organs Page 16 in Handouts  NIEMANN PICK’S DISEASE Symptoms: Swelling of endothelial, mesenchymal, and parenchymal cells of liver, lung, brain, bone marrow and spleen. Mental retardation, early death. Treatments: No specific treatment, organ transplantation, enzyme replacement, and gene therapy are possible ways. Page 16 in Handouts  CLASSES OF GLYCOLIPIDS Classification: oBased on the chemical structure, glycolipids are classified into two major and several sub-classes: Page 17 in Handouts  CLASSES OF GLYCOLIPIDS oNormally present in the outer surface of the cell membrane oThey are also present in the myeline sheath of central nervous system and spinal cord Page 17 in Handouts GLYCOLIPIDS  CEREBROSIDES Most abundant in the myelin sheath of nerves These are mainly a combination of ceramide and monosaccharides The C1 of monosaccharide linked with the C1 of ceramide in a β-linkage fashion Based on the type of monosaccharides attached to the ceramide, cerebrosides are classified into two sub-classes: Glucocerebrosides, Galactocerebrosides Further addition of monosaccharides to glucocerebrosides converts to more complex glycosphingolipids For example, blood group antigens are oligosaccharides which protein or ceramide linked through their reducing end The different antigens have different antigenic determinants at their non-reducing end Page 17 in Handouts CLINICAL CORRELATIONS - CEREBROSIDES Page 17 in Handouts  GANGLIOSIDES oFound in the ganglion cells of CNS oCeramides conjugated to galactose or glucose with several other carbohydrates, e.g. NAcGlu, NAcGalac or NANA (N-acetyl neuramic acid / sialic acid) Page 18 in Handouts  GANGLIOSIDES - ROLE a) GM1 is found in plasma membrane of intestinal mucosal membrane, binds to cholera toxin and activates cAMP cascade system where elevated cAMP levels results in secretion of isotonic fluid – diarrhea b) By similar mechanism, upon binding to diphtheria/tetanus toxin, results in inhibition of eukaryotic protein biosynthesis c) With the influenza, it is a specific ganglioside that binds to the virus and results in the first step of infection d) Also important in cell-to-cell recognition – results in regulation of natural killer cell cytotoxicity and mediating inflammation such as in recognition of a pathogen Page 19 in Handouts  – CLINICAL CORRELATION GAUCHERS DISEASE Due to inherited deficiency of glucocerebrosidase enzyme, glucocerebroside cannot be broken to cerebroside and glucose as a results these lipids are deposited in the several organs such lung, liver, spleen, brain etc. Sign and symptoms: 1. Megaly: painless hepatomegaly, spleenomegaly 2. Hypersplenism: rapid destruction of blood cells leading to anaemia, neutropenia, thrombocytopenia leading to increase risk of infection and bleeding 3. Liver cirrhosis, mental retardation, osteoporosis, yellowish-brown skin etc. Treatments: Enzyme replacement, Organ transplantation, Blood transfusion, Gene therapy, Antibiotics Page 17 in Handouts  – CLINICAL CORRELATION GAUCHERS DISEASE Due to inherited deficiency of glucocerebrosidase enzyme, glucocerebroside cannot be broken to cerebroside and glucose as a results these lipids are deposited in the several organs such lung, liver, spleen, brain etc. Sign and symptoms: 1. Megaly: painless hepatomegaly, spleenomegaly 2. Hypersplenism: rapid destruction of blood cells leading to anaemia, neutropenia, thrombocytopenia leading to increase risk of infection and bleeding 3. Liver cirrhosis, mental retardation, osteoporosis, yellowish-brown skin etc. Treatments: Enzyme replacement, Organ transplantation, Blood transfusion, Gene therapy, Antibiotics Page 17 in Handouts  – CLINICAL CORRELATION TAY SACH’S DISEASE An inherited disorder characterized by early death (2-3 years old) This disease results from a lack of an enzyme, hexosaminidase A, involved in the degradation of GM2 ganglioside or called Tay Sach’s gangliosides Signs and symptoms include mental retardation and paralysis, and characteristic cherry spot on eye or macula followed by blindness Treatments: enzyme replacement therapy, substrate reduction therapy, gene therapy Page 18 in Handouts  OTHER LIPIDS - TERPENES These are the derivatives of isoprene Isoprene is a 5 carbon-containing hydrocarbon with two double bonds A several number of 5 carbon isoprenes are join together to form terpenes such as Squalene (a precursor of cholesterol) Page 20 in Handouts OTHER LIPIDS - WAXES Page 20 in Handouts STEROIDS These compounds almost have the same general structure They contain a fused ring system of at least 3 six-membered rings (such as A, B, and C) and 1 five-membered ring (D) in their structures The precursor of this fused ring system is called – perhydrocyclopentanophenanthrene Page 20 in Handouts OTHER LIPIDS - CHOLESTEROL Widespread in biological membranes It has 27 carbons in its fused ring structure with only one hydroxyl (-OH) group at C3 position Hence, cholesterol is highly hydrophobic in nature Functions include: Important constituent of biological membranes It is precursor of several hormones such as sex hormones It is also the precursor of bile acids which play an important role in the digestion of fat in our system, regulates our blood pressure, pulse rate and body temperature Page 20 in Handouts OTHER LIPIDS - CHOLESTEROL Detrimental effects of cholesterol: In spite of several beneficial effects cholesterol has several detrimental effects in our system, such as hypercholesterimia or hyperlipidemia is a major risk factor of several diseases such as – high blood pressure  hypertension  brain stroke  Atherosclerosis  heart attack and  other cardiovascular diseases. Page 20 in Handouts CHOLESTEROL >>>> Page 21 in Handouts OTHER LIPIDS - WAXES These are the ester of fatty acids and alcohols (not glycerol) such as Myricyl palmitate (bee wax), triacontanyl palmitate Melting point of waxes is 60-100 oC which is much greater than the melting point of triglycerides (TG) Functions & Uses: Tropical plants got wax on their leaves to avoid excessive water evaporation Lanolin oil (from lamb wool) and bee wax are used in the cosmetic and pharmaceutical industries to make lotions, ointments, and polishes, etc. Page 20 in Handouts THE END