With water, I say, Touch me not ee ea Within limits, 1 am dutiful In excess, Lam dangero! ipids (Greek: lipos-fat) are of great importance to L the body as the chief concentrated storage form of energy, besides their role in cellular structure and various other biochemical functions. As such, lipids are a heterogeneous group oi compounds and, therefore, it is difficult to define them precisely. Lipids may be regarded as organic substances relatively insoluble in water, soluble in organic solvents (alcohol, ether etc.), actually or potentially related to fatty acids and utilized by the living cells Unlike the polysaccharides, proteins and nucleic acids, the lipids are not polymers (do not same Further, lipids are mostly small molecules. have repeating units/monomers) Lipidomics is a recent term used for the comprehensive study of lipids that includes chemistry, functions, metabolism, pathology and various other aspects. Classification of lipids Lipids broadly classified into simple, complex, derived and miscellaneous lipids, which are further subdivided into different groups are 1. Simple lipids : 2 ie these are mainly of two tYPES alcohols. These are main! ie a ils (triacylglycerols) + These (a) Fats and oils (riacyivcero esters of fatty acids oa The diterencé—Deiueen fat and —oil is only physical. Thus, oil is @ is a solid at room jiquid while fat temperature. Waxes: Esters of fatty acids (usually iong chain) with alcohols other than glycerol. These alcohols may be aliphatic alicyclic. Cety! alcohol is—-mast commonly found in waxes. Waxes are Used in the preparation of candles, lubricants, cosmetics, ointments, polishes etc 2. Complex (or compound) lipids: These are esters of fatty acids with alcohols containing additional groups such phosphate, nitrogenous base, carbohydrate, protein etc. They are further divided as follows (a) Phospholipids: They contain phosphoric acid and frequently a nitrogenous base. This is in addition to alcohol and fatty acids : (b) 29BIOCHEMISTRY oo 5. Lipids protect the internal organs, serve as terials and give shape and smooth {iy Glycerophospholipids : These phosoho- ioe cenian alvccrol_as.the alcoho! eg, lecithin, cephalin. spholipids : Sphingosine is (i. Sghingophospholipi: the alcohol in this group OF phosphe- Ipids €-8 ee (b) Glycolipids : These lipids contain a fatty nitrogenous base- aid. carbohydrate and nitrogene The_alcohol_is sphingosine, hence they aizalso_called_as_glycospl ingolipids. aTycerol “and phosphate are. absent &.3-, cerebrosides, gangliosides lecular complexes (c) Lipoproteins : Macromol S oF Tipids with protein: (@ quer complextipids: Sulilibids. 2° Ips and ipopolysacchatides ate-amors lipids and li the other complex lipids 3, Derived lipids: These a the derivatives obiail is, 0 FoTipids which possess _the fs. These inciude ghyceroland of ‘and diacylalycerols, lipid (fa are vitamins._steroid hormones, hydto- carbons and Ketone bodies. |, Miscellaneous lipids: These_include 2 large ‘Tumber_of compounds _possessiN® the Fe caeristics of lipids _e.[Link], ‘SHuilene, Bydrocarbons such as pentacosane (in bees wan), terpenes etc NEUTRAL LIPIDS: The lipids which are lipids. These uncharged are refered to as neutral li ‘and triacylelycerols, cholesterol ‘characteristics_o is, lipid are mono-, di-, and cholesteryl esters. Functions of lipids Lipids perform several important functions 1. They are the concentrated fuel reserve of the body (triacylglycerols) 2. Lipids are the constituents of membrane structure and regulate the _ membrane permeability (phospholipids and cholesterol. _ 3, They serve as a source of fat soluble vitamins (A, D, E and K). 4, Lipids are important as cellular metabolic regulators (steroid hormones and prostaglandins) insulating mat the body. appearance 10 acids with ids are carboxylic hy a bon ‘side chain. They are the simplest form of lipids. y occur in the esterified form yy various lipids. They are vesterified) fatty acids. uch simpler in origin Fatty acids main! Fatty acids structure in contrat ften contain group’ which of hydroxy and cyclopentane (MBS: Even and odd carbon fatty acids vr in natural ‘Most of the fatty [Link]-occut lipids are of even < ‘carbons (usually 14C- - 200). This is due to. the fact that. biosynthes' acids mainly occurs with the. sequential addition ee carbon units. Palmitic acid (16C) and Srearie acid (18C) are the most comene! Among, srertdd chain fatty acids, propionic acid (3C) ‘and valeric acid (5C) are well known Saturated and unsaturated fatty acids saturated ‘fatty acids donot contain_¢ double bonds, while unsaturated fatty acids contain one or more double bonds. Both saturated_and ansaturated fatty acids almost equally occur in the natural lipids. Fatty acids with one double unsaturated, and those with 2 oF bond are mono. more double bonds are collectively knowa as polyunsaturated fatty acids (PUFA) Nomenclature of fatty acids The naming of a fatty acid (systematic name) is based on the hydrocarbon from which it is derived. The saturated fatty acids end with a suitix -anoic (e.g., octanoic acid) while the unsaturated fatty acids end with a suffix -enoic32. double bonds, starting from the carboxyl end. Thus, saturated fatty acid, palmitic acid is writen a8 16 : 0, oleic acid as 18 : 1; 9, arachidonic acid a5 20: 4; 5, 8, 11, 14. There are other conventions of representing the double bonds. A? indicates that the double bbond is between 9 and 10 of the fatty acid. w 9 represents the double bond position (9 and 10) from the w end. Naturally occurring unsaturated fatty acids belong to @ 9, @6 and « 3 series Linolenic acid (18 : 3; 9, 12,15) 3 series 6 series Linoleic acid (18 : 2; 9, 12) and arachidonic acid (20 : 4; 5, 8, 11, 14) w9 series Oleic acid (18: 1:9) ‘The biochemically important saturated and unsaturated fatty acids are given in the Table 3.1. ESSENTIAL FATTY ACIDS ‘The fatty acids that cannot be synthesized by the body and, therefore,should be supplied in the diet are [Link]-essential fatty acids (EFA) Chemically, they are polyunsaturated fatty 5 namely linoleic acid (18 : 2; 9, 12) and 118; 3;-9,-12)-15).-Aeachidonic aa 20: 4; 5, 111d) becomes essential, if its precursor linoleic acid is not provided in the diet in sufficient amounts. The steuctures of EFA are given in the Table 3.1 Biochemical basis for essentiality : Linoleic acid and linolenic acid _are_essentidl since ‘anmans lack the enzymes that can introduce double bonds beyond carbons 9 to 10. Functions of EFA: Essential fatty acids are required for the membrane structure and ction, transport of cholesterol, formation of Iipoproteins, prevention of fatty _liver_ete. (Chapter 23). They are_also_needed (or the synthesis of another important group _of compounds, namely eicosanoids (Chapter 32) Deficiency of EFA: The deficiency of EFA results _in__phomodema —or toad sti Characterized by the presence of horny eruptions BIOCHEMISTRY H._(CH,)/COOH Hy ACHa/COOH i WA YCHa)CHy —-HyOtH0)7 “MH Olele acts Etaidic acid (rans orm) (aistorm) eS 3.1: Cistrans isomerism i Fie. rensaturated tatty acids ‘on the post ior and lateral pats of limbs. on the ev i buttocks, loss of hair and poor wound healing Conditionally essential fatty acids Certain fatty acids that become essential under some developmental or disease conditions conditionally essential are referred to as fatty acids, The most important among these is docosahexaenoic acid (DHA; «3 fatty acid; 22 : 6). ‘0 a limited Humans can synthesize DHA, acid (ALA). However, the extent, from a-linoleic capacity to convert ALA to DHA is limited in preterm infant. Therefore, supplementation of developing DHA is required to meet the needs of brain. Many infant nutrient formulas have DHA added to them. Fish oils are good sources of docosahexaenoic acid and eicosapentaenoic acid (EPA). Both of these are considered as heart disease fighting fatty acids. Isomerism in unsaturated fatty acids Unsaturated fatty acids exhibit geometric isomerism depending on the orientation of the groups around the double bond axis. If the atoms or acyl groups are present on the same side of the double bond, it is a cis configuration. On the other hand, if the groups ‘occur on the opposite side, it is a trans configuration. Thus oleic acid is a cis isomer while elaidic acid is a trans isomer, as depicted in Fig.3.1. Cis isomers are less stable than trans isomers. Most of the naturally occurring unsaturated fatty acids exist as cis isomers In the cis isomeric form, there is a molecular binding at the double bond. Thus, oleic acid3: LIPIDS oO ° CH-O-C Ay 3H,-O-" af |ncb-o-fe on 9 Reb-o- Hy-O-C Ry! HOH ‘THacylgtycerol 4,2-Diacylalyeerot 9 | jens rl tle OH HO-GH R-C-0-CH CHZOH CH,OH 1-Monoscylglycerol 2-Monoscyiglycero! Fig. 3.2 : Goneral structures of (For patnity! R= Cighhy for stearoy! = CiyPhs, FOr tnoleoy! Re Coty) exists in an L-shape while elaidic acid is a straight chain. Increase in the number of double bonds will cause more bends (kinks) and arachidonic acid with 4 double bonds will have a U-shape. It is believed that cis isomers of fatty acids with their characteristic bonds compactly pack the membrane structure. Hydroxy fatty acids : Some of the fatty acids are hydroxylated. B-Hydroxybutyric acid, one of the ketone bodies produced in metabolism, is a simple example of hydroxy fatty acids. Cerebronic acid and recinoleic acid are long chain hydroxy fatty acids. Cyclic fatty acid will Fatty acids with cyclic structures are rather rare e.g., chaulmoogric acid found in chaulmoogra oil (used in leprosy treatment) contains cyclopentenyl ring. Eicosanc : These compounds are related to eicosapolyenoic fatty acids and include prosta- sglandins, prostacyclins, leukotrienes and throm- boxanes. They are discussed together (Chapter 32) BULB van aly Trans fatty acids (TFA) possess double bonds and“are formed during hydrogenation (saturation) of natural oils. Further, small amounts of TFA are a0 formed in the rumen by the action of microorganisms on fat containing TFA. TFA are Widely used in food industry (iast foods and ready 10 eat packaged foods) to increase the shelf lie" oF various foods. 33 TFA are known to be hi 7 eaith.-as_tbeit_consumption is_asso- ny ‘increased risk of various ated _with. cites wg aba anf ear wo alevated LOL, reduced HDL etc ee are TFA containing foods should be avoided in the diet. a ine is the most commonly use nae vetaining fat in food industry. In recent years, with improved technology, oft margarine with low TFA content has been developed. However, the warning of health risk on TFA containing foods consumption continues. ears) iacylglycerols_ (formerly. triglycerides) are pe see of glycerol with fatty acids. The fats and oils that are widely distributed in both plants agdanimals are _chemically_triacylghycerols, ‘They_are insoluble in water_and_non-palarin character and. commonly known as neutral fats Fats ae stored fuel : Triacylglycerols are the most abundant. group of lipids. that_primarily function as fuel reserves of animals. The fat reserve of normal humans (men 20%, women 25% by weight) is sufficient to meet the body's caloric requirements for 2-3 months. Fats primarily occur in adipose tissue : Adipocytes of adipose tissue—predominantly found in the subcutaneous layer_and in the abdominal cavity—are specialized for storas triacylglycerols. The fat is stored in the form of globules dispersed in the entire cytoplasm. And surprisingly, triacylglycerols are not the structural components of biological membranes. Structures of acylglycerols: Monoacyl- alycerols, [Link]—tciacylglycerols respectively consisting of one, two and three mole- cules of fatty acids esterified to a molecule of gly- efol, are known (Fig.3.2). Among these, triacyl- glycerols are the most important biochemically. Simple triacylglycerols contain the same type of fatty acid residue at all the three carbons e.g. tristearoyl glycerol or tristearin. ~4 Medical Concepts/ Clinical Correlates. © Upids are important to the body as constituents (of membranes, source of fat soluble (A, 0, E ‘and K) vitamins and metabolic regulators (steroid hormones and prostaglandins). adipose tissue are ‘the body. Fats found in the subcutaneous tissue ‘and around certain organs serve as thermal Insulators. ‘e- The unsaturated fatty acids-linolel and linolenic ‘add—are essential to humans, the deficiency of which causes phrynoderma or toad skin. Mixed_triacylglycerols_are_more_common. They contain 2 or 3 different_types of fatty-acid {ekidues. In genera, fatty acid attached to C; is saturated, that attached to Cy is unsaturated while that on C; can be either. Triacylglycerols are named according to placement of acyl radical on lvcerol eg, 1,3-palmitoyl 2-linoleoyl glycerol Triacylglycerols of plants, in general, have higher content of unsaturated fatty acids compared to that of animals. Stereospecific numbering of glycerol The structure of glycerol gives an impression that carbons 1 and 3 are identical. This is not true in a 3-dimensional structure. In order to represent the carbon atoms of glycerol in an unambiguous manner, biochemists adopt a _ stereospecific ‘numbering (sn) and prefix glycerol with sn [Link] HOCH HOH sn iycerol It should be noted that Cy and C, are different. Cells possess enzymes that can distinguish these two carbons. Thus glycero- kinase phosphorylates sn-3 (and not snl) slycerol to give sn-glycerol 3-phosphate PROPERTIES OF TRIACYLGLYCEROLS, ‘A few important properties of triacylalycerol have biochemical relevance, which ate discussed below 1. Hydrolysis: Triacylalycerols.—underge stepwise enzymatic hydrolysis to finaly liberate free fatty acids and glycerol. The process of hydrolysis, catalysed by lipases is important for digestion of fat in the gastrointestinal tract ang fat mobilization from the adipose tissues, 2. Saponification : The hydrolysis of triacyl. slycerols by alkali to produce glycerol and soaps is known as saponification Triacylglycerol + 3 NOH —> Glycerol + 3 R-COONa (soaps) 3. Rancidity : Rancidity is the term used to represent the deterioration of fats and oils resulting in an unpleasant taste. Fats containing tnsaturated fatty acids are more susceptible to rancidity. Rancidity occurs when fats and oils are exposed to ait, moisture, light, bacteria etc Hydrolytic rancidity occurs due 10 partial hydrolysis of triacylglycerols by bacterial enzymes, Oxidative rancidity is due to oxidation of unsaturated fatty acids. This results in the formation of unpleasant products such as dicarboxylic acids, aldehydes, ketones etc. Rancid fats and oils are unsuitable for human consumption. Antioxidants : The substances which can prevent the occurrence of oxidative rancidity fare known as antioxidants. Trace amounts of antioxidants such as tocopherols (vitamin £), hydroquinone, gallic acid and a-naphthol are added to the commercial preparations of fats and oils to prevent rancidity. Propyl gallate, butylated hydroxyanisole (BHA) and butylated hydroxy- toluene (BHT) are the antioxidants used in food preservation. 4, Lipid peroxidation in vivo: In the living cells, lipids undergo oxidation to produce peroxides and free radicals which can damage the tissue. The free radicals are believed to cause inflammatory diseases, ageing, cancer, atherosclerosis etc. It is fortunate that the cells ‘possess antioxidants such as vitamin E, urate andChapter 3 : Liping 35 a superoxide dismut Peroxidation (Chapter on in vivo lipid Tests to check of fats and oils lodine number Pt is def (number) of iodine lefined as the grams oil. lodine n absorbed by 100 g of fat Unsatration of ag tf Know the relative tot! , 's directly proportic twee ent Ta unsaturation he abet ls the dere o n oils/fats are given below. vol, —___ I cocoa gt line number Butter 7 10 Palm ol 3-2 Olive oi ae Groundnut oi 85 — 100 Cottonseed oil 100 — 110 Sunflower oil fae Linseed oil 175 — 200 ae S200 Determination of iodine number will help to know the degree of adulteration of a given oil Saponification number : It is defined as the img (number) of KOH required to hydrolyse (saponify) one gram of fat or oil. Saponification number is a measure of the average molecular size of the fatty acids present. The value is higher for fats containing short chain fatty acids. The saponification numbers of a few fats and oils are given below Human fat: 195-200 Butter 230-240 Coconut oil : 250-260 Reichert-Meiss! (RM) number : It is defined as. the number of ml 0.1 N KOH required to completely neutralize the soluble volatile fatty acids distilled from 5 g fat. RM number is useful in testing the purity of butter since it contains a good concentration of volatile fatty Se ie acid, caproic acid and on acid). conta toot volte faty acts, Suter fas mtn aie TM 3TY st other ; vs acon of butter can be easily tested Y this sensitive RM number Acid number : It i defined as the cures mg of KOH required to completely a ae free fatty acids present in one gram if od In normal circumstances, refined oils fi ie be free from any free fatty acids. ol _o decomposition—due to chemical or = contamination—yield free fatty acids. Logs ra oils with increased acid number are unsafe for human consumption. Pe al These_are_complex_or_compou! cont rm ic_acid, in addition to fatty acids, nitrogen ‘and_alcohol (Fig.3.3). There are two classes of phospholipids 1. Glycerophospholipids_or_phaspbagluce- rides) that contain glycerol_as the alcohol. rides) that contain gl ohol., 2. Sphingophospholipids (or sphingomyelins) that confarn sphingosine as the alcobal. Glycerophospholipids Glycerophospholipids are the _major_lipids that occur in biological membranes. They consist of glycerol 3-phosphate esterified at its Cy and Cy with “fatty acids. Usually, C, contains a saturated fatty acid while C, contains an unsaturated fatty acid 1. Phosphatidic acid: This is the_simpJest phospholipid. It does not occur in good concen- tration in the tissues. Basically, phosphatidic acid is an intermediate in the synthesis _of triacylglycerols and phospholipids. The other glycerophospholipids containing different nitrogenous bases or other groups may be regarded as the derivatives of phosphatidic acid,Chapter 3 : LIPIOS ‘Trans fatty acids, widely used In food industry, ‘are detrimental to health-inked with Increased risk of diabetes, heart diseases etc, Fats and lls on exposure to ai, moisture, bacteria ete. undergo. rancidity.(deteroration), ‘This can be prevented by the addition of certain antioxidants (vitamin, hyéroau as in E, hydroquinone, gale Une most abundant [Link] phospholipids. inahe cel membrangsen Chemically, lecithin (Greek lecithos—ege yolk) _is a_phosphatidic_acid SOT motne 3 the Base. Floss as (Speen ihe sere on | is_an__ important Fosphattdyleholine Young Wr Tones at acts as_a surfactant (details given later) (b) tYsolecithin is formed by removal faffy_acid either at C; of C, of lecithin. 3. Cephalins _(phosphatidylethanolamine) Ethanolamine is the nitrogenous base present ip cephalins. Thus, lecithin and cephalin differ with regard to the base. J Phosphatidylinositol: The stereoisomer myo-inositol is attached to phosphatidic acid to ive phosphatidylinositol (PN). This is an important component of cell membranes. The action of Gertain_hormMORES (€.g. Oxytocin, vasopressin) is niediated through PI SX Phosphatidylserine: The amino _acid serine is present in this group of glycerophos- pholipids. Phosphatidylthreonine is also found in ‘Tetain_tissues_and plays a role in apoptosis (programmed cell death). 6. Plasmalogens: When a fatty acid is attaché by an ether linkage at C, of glycerol in the glycerophospholipids, the resultant compound is*plasmalogen. Phosphatidal-ethanolamine is the host Important which is similar in structure to Phosphatidylethanolamine but for the ether 7 Tinkage (in place of ester). An unsaturated fatty FeRPaeTurs at Cy. Choline, inositol and serine ‘nay substitute ethanolamine to ive plasmalogens. 7. + Mis so namet fiyst isolated _from.heark- My two—molecules—af Jn additional glycerol —animpasiat iiMiolipin_consists of ‘hosphatidic acid held by Trough phosphate grounselt—ts. Kua ant miactondza_ mente ecu shes miockondeal_membas ‘and essential for_mitoch« eT olin. levels-may result_in Wochondiiat__ dysfunction, i jidism, _cardioskelet. ‘myopathy Barth ae Caolipin’ We only phospho- flvceride that possesses antigenic properties. In recent years, detection of anticardiolipin antibodies is used as a diagnostic tool in tie evaluation of embryo transfers (in assisted reproductive technology) and organ transplan- tation. ‘Sphingomyelins Sphingosine is an_amino_alcohol_present_in sphingomyelins (sphingophospholipids). They do not contain glycerol at all. Sphingosine is attached by an amide linkage. to a fatty acid to produce. Ceramide. The alcohol group. of sphingosineis Bound to phosphorylcholine in sphingomyelin “Structure (Fig.3.3). Sphingomyelins. are important constituents of myelin and are found in good quantity in brain and nervous tissues. It's believed that sphingomyelins are involved in cell signaling, and in apoptosis. Ceramide, acts as a second messenger (signaling molecule) by regulating programmed cell death (apoptosis), cell cycle and_cell differentiation. A cermide containing a 30-carbon fatty acid is a major component of skin, and it regulates skin’s water permeabi Functions of phospholipids ~ + |’ Phospholipids constitute an important group of compound lipids that perform a wide variety of functions 1. In association with proteins, phospholipids form the structural components of membranes and regulate membrane permeabilityBIOCHEMISTRY wo Sohingcsne — on CHy~(CH3)y2—CH=CH~ CH,OH | —o. HO 4) . oR Wa oH 2. Phospholipids (lecithin, cephalin and cardiolipin) in the mitochondria maintain the conformation of electron transport components, and thus cellular respiration 3. Phospholipids participate in the absorption of fat from the intestine. 4. Phospholipids are essential synthesis of different lipoproteins, participate in the transport of lipic 5. Accumulation of fat in liver (fatty liver) can be prevented by phospholipids, hence they are regarded as lipotropic factors. e arachidonic acid, an unsaturated fatty acid liberated from phospholipids, serves: as a precursor forthe synthesis of eicosanoids (prosa- flandins,prostacyclins,thromboxanes et) 7. Phospholipids participate in the reverse cholesterol transport and thus help in the removal of cholesterol from the body. 8, Phospholipids act as surfactants (agents lowering surface tension). For instance, dipalmitoy! phosphatidylcholine is an important Jung surfactant. 9. Cephalins, an important group of phospho- lipids participate in blood clotting. 10. Phosphatidylinositol is the source of second messengers—inositol triphosphate and, diacylglyceol, hat are involved in the action of some hormones. Lung surfactant Lung surfactant is mainly composed of phospholipid-dipalmitoy! lecithin, some proteins ‘and carbohydrates. Dipalmitoyl lecithin is largely responsible for lung surfactant action (i.e., for the and thus GH-CH-NH- “34+ Stare of gatactascoraide (A = Ft 2 & cmon) (CHa) serebronic 2 eatty 010) cH 0-H, OF. —ragancenspowai A 6 Sate ® ner surfaces of lungs), ince of in pret pe oranda Infant respiratory distress syndrome (IRDS) in premature infants is due fo the absence of lung This is caused by inability of immature vynthesize dipalmitoy!Fecithin in (1/5) ratio of amniotic sturity. During the uid is an indicat ae fal growth (up to 26th week), course of eatly fet lung synthesizes more ‘sphingomyelin, and later term healthy infant, nore lecithin. Thus, for a full dn L/S ratio above 2 indicates full lung maturity. 2 Ts ratio (<1) results in IRDS, a comm” Cauce of neonatal morbidity. IRDS is treated by rtificial surfactants. ‘administration of natural or ai cap Glycolipid (glycosphingolipids) are important conatituents_of cell_membrane and nervous ewes (particularly the brain), They occur as cell surface carbohydrates to form glycocalyx in plasma membranes. — Cerebrosides are the STipids. They contain a ceramide (sphinggsine glycolipi attached to a fatty acid) and one or more sugars. Galectocerebroside _ (galactosylceramide] and glucocerebroside are the most _impagtant slycolipids, The structure of galactosylceramide is given in Fig.3.4. It contains the fatty acid cerebronic acid. Sulfagalactosylceramide isthe silfalide derived trom galactosylceramide. Gangliosides : These are predominantly found in ganglions and are the most complex form of alycosphingolipds. They are the derivatives of lungs to Lecithin/sphingo™) itor of fetal mat of for simplestChapter 3 : LIPIDS, + Me shuld dpa in reves rerence of inner surface of the lungs, the absence of which s asmusned nt, Fesplratory distress syndrome in infants © Lecthishingomyein (YS) rato of annoc uid Is an indicator of fetal maturity. /S rato above 2 indicates full ung maturty. * Cephalins participate in blood doting. -erebtosides and contain one or more molecu! 1in one or more molecules of Neacetvin icid (NANA), the iMportant sialic acid, The structure of NANA is 8iven in carbohydrate chemistry (Refer Fig.2.10) ne Me most important gangliosides present in the brain are GM,, GM,, GD, and GT, (G represents ganglioside while M, D and T indicate mono-, di- or tri sialic acid residues, and the number denotes the carbohydrate sequence attached to the ceramide). The ganglioside, GM, that accumulates in Tay-Sachs disease is represented next (outline structure). Ceramide Glucose [Galactose] N-Acetyl- N-Acetyl galactosamine rneuraminic acid Globosides : A type of glycolipids with two or more sugars linked 10 ceramide the sugars usually present are glucose and galactose. Lactosylceramide (ceramide-galactose-glucose) is present in erythrocyte membrane. Peay Lipoproteins are molecular complexes of lipids with proteins. They are the transport vehicles for lipids in the circulation. There are five types of cron, lipoproteins, namely hylan ow density (VLDL) . lipoproteins (LDL), by — (HDL) and free fatty 200°" Their structure, SeParater” diseases are discussed (08 ds containin 2 un ; voids are the compounds O° namely arts Mt a are rings A B CPrsiats of 2 phenanthrene nucleus caea snd ¢) to which a cyclopenta Ter PPP are ‘The structure and numbering, of Cl resents shown in Fig.3.5. The steroid nucleus room ae crowed carbons, unless sPeCIHEAY 5 ang double bonds. The methyl side | page eg Ta) attached to carbons 10 and 13 are S00 single bonds. At carbon 17, steroids contain a side chain. i ical ‘There are several steroids in the bioloBie® system. These include cholesterol, bile 260% vitamin D, sex hormones, adrenocorticn, hormones, sitosterols, cardiac glycosides ane’ alkaloids. If the steroid contains ‘one of mot hydroxyl groups it is commonly known 35 sterol (means solid alcohol) CHOLESTEROL Cholesterol, exclusively found in animals, is the most abundant animal sterol. It is widely distributed in all cells and is a major component of cell membranes and lipoproteins. Cholesterol (Greek ; chole-bile) was first isolated from bile. Cholesterol literally means ‘solid alcohol from bile. Structure and occurrence The structure of cholesterol (Cy7Hyg0) is depicted in Fig.3.5. It has one hydroxyl group at Cy and a double bond between C; and Cy ‘An 8 carbon aliphatic side chain is attached to yz. Cholesterol contains a total of 5 methyl groups‘a: METABOLISM OF LIPIOS i SOO RR Choesterot Wg —— Apoprtein oy |< — Prospoin Neutra coe a1 T a cel Ve traeyyoort . (+ chotesterat ester }$—_—— sre (coat) Tyg A general structure of Ipoproten compen. 1 14 pe sake of C8), Onl a pat ofthe shod ‘snd core ar filed withthe constvents). Mata) Lipoproteins are molecular complexes that const of lipids and proteins (conjugated rateins). They function as transport vehicles for fois in blood plasma. Lipoproteins deliver the iid, components (cholesterol, triacylglycerol atc) 10 various tissues for utilization Structure of lipoproteins A lipoprotein basically consists of @ neutral fipid core (with triacylglycerol and/or cholestery| ester) surrounded by 2 coat shell of phospho- lipids, apoproteins and cholesterol (Fig. 14.35) The polar portions {amphiphilic} of phospho- lipids and cholesterol are exposed on the surface of lipoproteins so that lipoprotein is soluble in aqueous solution Classification of lipoproteins Five major classes of lipoproteins are identified in human plasma, based on their separation by electrophoresis (Fig. 14.36). 1. Chylomicrons : They are synthesized in the intestine, and transport exogenous (dietary) tiacylglycerol to various tissues, They consist of highest (99%) quantity of fipid and lowest (1%) concentration of protein. The chylomicrons are the least in density and the largest in size, among the lipoproteins, 2. Very low density lipoproteins (VLDL) = They ate produced in liver and intestine and are 9 Fesponsible for the transport of endogenously synthesized triacylglycerols 3. Low density lipoproteins (LDL) : They are formed from VLDL in the blood circulation. they transport cholesterol from liver to other tissues 4. High density lipoproteins (HDL) : They are ‘mostly synthesized in liver. Three different fractions of HDL (1, 2 and 3) can be identified by ultracentrifugation. HDL particles transport cholesterol from peripheral tissues to. liver (reverse cholesterol transport 5. Free fatty acids—albumin : Free fatty acids in the circulation are in a bound form to albumin. Each molecule of albumin can hold about 20-30 molecules of free fatty acids. This lipoprotein cannot be separated by electro- phoresis Apolipoproteins (apoproteins) The protein components of lipoproteins are known as apolipoproteins or, simply, apoproteins. ‘They perform the following functions 1. Actas structural components of lipoproteins. 2. Recognize the cell membrane surface receptors, 3, Activate enzymes involved in lipoprotein metabolism, The comparative characteristic features of different lipoproteins with regard to electro- (-) Cathode | | VLDL (pre-f-lipoprotein) la (Anode Fig. 14.36 : Electrophoresis of plasma (serum) Spoprotens.