UIT (11) MLEULES F LIFE: LIPIDS AD PTEIS 11.1 Types f Lipids Lipids are als bichemical cmpunds that cntain carbn, hydrgen, and xygen. But lipids, unlike carbhydrates, share n cmmn structural features. The definitin f a lipid is mre functinal r peratinal. Lipids are bimlecules that are insluble in water but sluble in rganic slvents. We will classify lipids int tw majr categries: fatty-acid cntaining lipids and nnfatty acid cntaining lipids. Lipids fatty acid cntaining lipids nnfatty acid cntaining lipids fats and ils waxes phsphlipids sterids 11.2 Fatty Acids The fundamental building blcks f many lipids are lng-chain carbxylic acids called fatty acids. Fatty acids always cntain an even number f carbn atms and typically range between 10 and 20. This is a direct result f the bisynthetic pathways used t prduce fatty acids. The fatty acids can be saturated, mnunsaturated, r plyunsaturated. A saturated fatty acid cntains nly carbn-carbn single bnds in the hydrcarbn chain. A mnunsaturated fatty acid cntains ne = duble bnd in the hydrcarbn chain. A plyunsaturated fatty acid cntains tw r mre = duble bnds in the hydrcarbn chain. Table 11.1 lists the names and structures f cmmn fatty acids ften fund in lipid structures. 11-1
Fatty acid general structure palmitic acid 16 14 15 13 12 11 10 9 8 6 4 7 5 3 2 1 3 -( 2 ) 6-2 2 - ( 2 ) 6 - leic acid "the cis ismer" Table 11.1 mmn Saturated and Unsaturated Fatty Acids umber f carbn atms umber f duble bnds ame Frmula Surce 12(12:0) 0 Lauric 3 ( 2 ) 10 2 ccnut acid 14(14:0) 0 Myristic 3 ( 2 ) 12 2 nutmeg acid 16(16:0) 0 Palmitic 3 ( 2 ) 14 2 palm acid 16(16:1) 1 Palmitleic acid 3 ( 2 ) 5 =( 2 ) 7 2 macadamia nuts 18(18:0) 0 Stearic 3 ( 2 ) 16 2 lard acid 18(18:1) 1 leic acid 3 ( 2 ) 7 =( 2 ) 7 2 lives 18(18:2) 2 Linleic acid 18(18:3) 3 Linlenic acid 3 ( 2 ) 4 (= 2 ) 2 ( 2 ) 6 2 safflwer 3 2 (= 2 ) 3 ( 2 ) 6 2 flax 11.3 The Structure f Fats and ils Animal fats and vegetable ils are lipid esters knwn as triglycerides. ecall frm unit 9 that esters are made up f an acid part and an alchl part. The acid part f the lipid esters are fatty acids and the alchl is glycerl. 2 - - 2 - Glycerl (Glycerin) 11-2
Glycerl (lder name glycerin) is a small chain alchl cntaining three carbns with a hydrxyl (-) grup bund at each carbn. A single mlecule f glycerl can react with up t three fatty acid mlecules, ne at each grup. A mnglyceride cntains ne fatty acid attached t glycerl, a diglyceride cntains tw fatty acids and a triglyceride cntains three fatty acids. Mst naturally ccurring triglycerides cntain three different fatty acids and are called mixed triglycerides. Althugh the fatty acid chain length can vary in mixed triglycerides, they tend t be all saturated r unsaturated. Triglycerides cntaining saturated fatty acid chains and unsaturated chains n the same mlecule are rare. The type f fatty acid present in a triglyceride influences its physical appearance. Fats are triglycerides cntaining saturated fatty acids and are slids at rm temperature, ie: lard, while ils cntain unsaturated fatty acids and are liquids at rm temperature. This is a direct result f the packing ability f the triglycerides. Saturated chains can pack clse tgether because there are n carbn-carbn duble bnds t disrupt the linear nature f the chains. The result is a slid. In cntrast, unsaturated chains are kinked by a cis-cnfrmatin f the carbn-carbn duble bnd. This prevents unsaturated chains frm packing clsely tgether. The result is a liquid. Unsaturated fats can als have a trans-cnfiguratin. Mst peple generally recgnize unsaturated fats as a healthy alternative t saturated fats. wever, trans-fats are nt required by the bdy and d nt prmte gd health because they have a packing ability cmparable t saturated fats. But technically they are unsaturated and therefre can easily mislead cnsumers seeking unsaturated fats in their daily diet. This is the reasn mst fd prducers must nw specify the cntent f trans-fat in their prducts. G l y c e r l Fatty acid Fatty acid Fatty acid A generalized frmula f a triglyceride can be shwn as: 2 -- --' 2 --'' 11-3
Wrked Example 11-1 Write an equatin fr the esterificatin f glycerl with three mlecules f stearic acid. Slutin 2 + --( 2 ) 16 3 2 --( 2 ) 16 3 + --( 2 ) 16 3 --( 2 ) 16 3 2 + --( 2 ) 16 3 2 --( 2 ) 16 3 glycerl three stearic acids glyceryl tristearate + 3 2 11.4 hemical Prperties f Fats and ils The chemical reactins f fats and ils are the same as thse discussed fr esters (unit 9, hydrlysis f esters)) and alkenes (unit7, hydrgenatin f alkenes). 1. Sapnificatin (sap making) Triglycerides (fats r ils) can be hydrlyzed (brken dwn) t prduce glycerl and three fatty acids. When a strng base is used (ie; a), glycerl and the sdium salts f the fatty acids are prduced. The sdium salts f fatty acids are called saps. Fats r il + strng base glycerl + sap Fr example, the sapnificatin f glyceryl tripalmitate (tripalmitin, frm palm il) prduces sdium palmitate (a sap) accrding t the fllwing reactin: 2 --( 2 ) 14 3 --( 2 ) 14 3 + 2 3 a + - + 3 3 ( 2 ) 14 - a + 2 --( 2 ) 14 3 2 3 sdium palmitate (sap) tripalmitin glycerl 11-4
2. ydrgenatin ecall frm unit 7 that duble bnds in alkenes can be reduced t single bnds by reacting the alkenes with hydrgen ( 2 ) in the presence f a catalyst. arbn-carbn duble bnds in unsaturated fatty acids f triglycerides can underg the same reactin. (2 ) n unsaturated fatty acid + 2 catalyst i ( 2 ) n saturated fatty acid In a cmmercial applicatin called partial hydrgenatin, vegetable il is treated with hydrgen, but the reactin is stpped befre all f the duble bnds have been remved. mplete hydrgenatin wuld prduce a very brittle prduct; whereas partial hydrgenatin changes the il t a sft semi-slid fat. 11.5 Waxes Waxes are simple lipids that, like ils and fats, are als esters f fatty acids. wever, the alchl prtin f a wax is derived frm lng-chain alchls (12-32 carbns) rather than glycerl. mpare the wax structure belw with that f a triglyceride. te the presence f lng hydrcarbn chains n each side f the ester functinal grup in waxes. Wax: Fatty acid Lng-chain alchl A fatty acid A lng chain alchl 3 ( 2 ) 14-2 ( 2 ) 28 3 3 ( 2 ) 14-2 ( 2 ) 28 3 A wax ester (beeswax) 11-5
11.6 Phsphglycerides Phsphglycerides are a family f lipids that are similar t glycerides except that ne grup f glycerl is replaced by the ester f phsphric acid and an aminalchl. G l y c e r l Fatty acid Fatty acid Phsphric acid Aminalchl 11.7 Sterids Structurally, sterids are easily recgnized because they all cntain a characteristic furfused ring system; three cyclhexane rings and ne cyclpentane ring. Each carbn f a sterid mlecule is numbered and each ring carries a letter designatin. 12 13 17 11 1 D 16 9 10 2 14 15 A B 8 3 4 5 7 6 Sterid ring system The mst abundant sterid fund in the human bdy, and the mst imprtant, is chlesterl. 2 3 3 3 3 12-13 17 2-2 - 2-3 11 1 9 D 16 3 10 14 15 A B 8 4 5 7 6 chlesterl 11-6
The l ending in chlesterl indicates an alchl functinal grup, this is lcated n carbn 3. tice the fllwing: A hydrxyl ( ) grup n carbn 3. A methyl ( 3 ) grup n carbn 10. A methyl ( 3 ) grup n carbn 13. A duble bnd between carbns 5 and 6. A carbn chain at carbn 17. In humans, mst sterids functin as hrmnes, pwerful chemical messengers that transprt signals frm ne cell t anther. There are tw main classes f sterid hrmnes: the sex hrmnes and the adrencrtical hrmnes. Sex hrmnes cntrl reprductin and secndary sex characteristics and adrencrtical hrmnes regulate numerus bichemical prcesses. Sex rmnes Majr grups Bilgical effects Mst imprtant Estrgens Female sex hrmnes Estrne and Estradil Prgestins Pregnancy hrmnes Prgesterne Andrgens Male sex hrmnes Teststerne and Andrsterne 11-7
3 3 estrne estradil 3 3 3 prgesterne 3 3 3 3 teststerne andrsterne 11-8
PTEIS The wrd prtein is derived frm the Greek wrd prteis, meaning first, an indicatin f the imprtance f these substances. Prteins play an imprtant rle in a variety f bilgical systems, ie: xygen transprt, cmpnents f skin and hair, muscle mvement, as bilgical catalysts (enzymes), regulate metablic prcesses (hrmnes), and the list ges n and n and n. Prteins are large cmplex plymers f amin acids, the mnmeric unit f prteins. Amin acids are cnnected by an amide linkage called a peptide bnd. ur study f prteins begins with a survey f amin acids cmmnly fund in prteins. 11.8 The Amin Acids Amin acids are rganic mlecules that cntain an amin grup and a carbxyl grup. The amin acids in prteins are called alpha (α)-amin acids because the amin grup is attached t the α-carbn. A carbn cnnected t any carbxylic acid carbn is termed an α-carbn. Amin acids as are generally represented using the fllwing frmula: alpha carbn carbxylic acid grup 2 amin grup the side chain All amin acids (except prline) cntain, - 2, and bund t the α-carbn. They are differentiated by the side chains (called -grups) als bund t the α-carbn. 11.9 lassificatin f Amin Acids The difference between amin acids depends n their side-chain grups because this is the nly pint f difference (all amin acids cntain a carbxyl grup, an amin grup, and a ). The mst imprtant characteristic f grups is plarity. As a result, amin acids are classified int fur grups: nnplar, plar acidic, plar basic, and plar-neutral amin acids. Amin acids are knwn by cmmn names and each is abbreviated using a three-letter cde. The 20 amin acids cmmnly used t make prteins are listed in the fllwing table. 11-9
nplar Amin Acids 2 2 2 3 3 3 Glycine (Gly) Alanine (Ala) Valine (Val) 2 2 2 2 3 2 3 2 2 3 3 S Leucine (Leu) Islucine (Ile) 3 Methinine (Met) 2 2 2 2 Prline (Pr) Phenylalanine (Phe) Tryptphan (Trp) 11-10
Plar-Acidic Amin Acids 2 2 2 2 Aspartic acid (Asp) 2 Glutamic acid (Glu) Plar-Basic Amin Acids 2 2 2 2 2 2 2 2 2 2 2 2 Lysine (Lys) 2 Arginine (Arg) istidine (is) 11-11
Plar-eutral Amin Acids 2 2 2 2 2 3 S Serine (Ser) Threnine (Thr) ysteine (ys) 2 2 2 2 2 2 2 2 Tyrsine (Tyr) Asparagine (Asn) 2 Glutamine (Gln) 11.10 Amin Acid Stereismers All α-amin acids, except glycine, are chiral because the α-carbn is bund t fur different grups. Glycine is exempt because it has tw hydrgen atms attached t the α- carbn (recall chiral carbns must have fur different grups attached). As chiral mlecules, amin acids can exist as D r L ismers (recall unit 10). When writing Fischer prjectins fr amin acids, the - grup is always written at the tp and the grup at the bttm. If the 2 is n the Left we have the L- ismer, if it is n the right, we have the D- ismer. In bilgical systems, nly L ismers are fund in prteins. An example: L-Alanine, and D-Alanine 2 3 L-Alanine 2 3 D-Alanine 11-12
11.11 Amin Acids as Acids and Bases Amin acids cntain an acidic grup (-) and a basic grup ( 2 ). Basic grup 2 Acidic grup The carbxylic acid () has a tendency t dnate + and the amine grup ( 2 ) has a tendency t accept +. The prduct f this internal acid-base reactin is a diplar in (tw ples) called a zwitterin (frm the German meaning duble in ). When the carbxylic acid dnates + it becmes carbxylate ( - ). Therefre, the name indicates whether + is present (carbxylic acid) r absent (carbxylate). Fr example; glutamic acid ( + present n carbxylic acid) and glutamate ( + absent). 2 3 + _ Zwitterin Zwitterins are simultaneusly electrically charged and electrically neutral. They cntain psitive and negative charges that cancel resulting in a net charge f zer. Zwitterins are the neutral frm f the amin acid despite the presence f in in the name. Zwitterins gain + in acidic slutins and lse + in basic slutins. + + 3 3 + _ - 2 _ 11-13
At a certain p the psitive and negative charges f an amin acid are equal resulting in an verall net charge f zer. This p is called the iselectric pint (pi), nly the neutral frm f the amin acid (zwitterin) exists at the pi. Wrked Example 11-2 The pi value fr an amin acid is 6.0. Draw the general frm f the amin acid that predminates in slutin at each f the fllwing p values: a) p < 1 b) p = 6.0 c) p > 12 Slutin At lw p ( p<1) bth amin and carbxyl grups are prtnated giving an verall charge f 1+. At high p (p>12) bth grups have lst their prtns giving an verall charge f 1 -. Zwitterin present at p = pi. 3 + 3 + 3 + 3 + (a) b) c) - - - 2 p < 1 p = 6.0 p > 12 (charge =1+) (charge = 0) (charge =1-) Zwitterin - 11.12 The Peptide Bnd Individual amin acids in a prtein mlecule are linked by peptide bnds. A peptide bnd frms when a carbxylic acid frm ne amin acid reacts with the amin grup f anther amin acid. Peptide bnd is the name that bichemists give t the amide bnd. 3 + - + 2 3 + - + amin acid 1 amin acid 2 3 + - dipeptide 11-14
If three amin acid residues are present in a mlecule, it is a tripeptide; if fur, a tetrapeptide; and s n. It is wrth nting that nce amin acids are cnnected, we n lnger call them amin acids, instead, we refer t the bnded units as residues. amin acid amin acid amin acid amin acid peptide bnd All peptide chains will have an amin grup at ne end (a free, unbund - 3 + ) and a carbxylate at the ther (a free - ). By cnventin, we draw peptides and prteins with the -terminal (unreacted r free amin grup) n the left end f the peptide chain and the -terminal (the carbxylate grup) n the right end f the plypeptide. Peptides are named by listing the amin acid residues in rder frm the - t -terminal. Fr example, a dipeptide culd be written as (Ala-Gly), a tripeptide as (Thr-Gly-Ala), and a pentapeptide as (Lys-is-Ala-Thr-Gly). Wrked Example 11-3 Explain why the ntatin Gly-Ala and Ala-Gly represent tw different mlecules. Slutin Gly is the -terminal end f Gly-Ala and Ala is the -terminal end f Ala-Gly. 11.13 Prtein Structure In general, prteins are defined as plypeptide chains having 50 r mre amin acids. Prtein structure is described using fur levels f rganizatin: primary, secndary, tertiary, and quaternary structure. The Primary Structure f Prteins The primary structure f a prtein is simply the sequence f amin acids that makes up the peptide chain. We shw a segment f a prtein that cntains leucine, glutamine, asparagine, tyrsine, cysteine, and asparagines as: Leu Glu Asn Tyr ys Asn 11-15
The Secndary Structure f Prteins Prteins fld r align in a cnsistent manner which generates specific repeating patterns. These patterns are referred t as secndary structures. There are tw cmmn types f prtein secndary structures: the alpha helix (α-helix) and the beta pleated sheet (β-pleated sheet). ydrgen bnding is respnsible fr the secndary structure f prteins. α-helix: An α-helix is basically a spring-like structure stabilized by hydrgen bnds frmed between a carbnyl xygen and an amin hydrgen separated by 4 amin acid residues. This bnding hlds the plypeptide chain in the helical shape. arbxyl Terminal Amin Acid = n + 4 Amin Acid = n ydrgen Bnd 3 Amin Terminal β-pleated sheet: A less cmmn type f secndary structure is called a β-pleated sheet. β-pleated sheets frm when prtins f the plypeptide chain align side by side in a sheet-like array held tgether by hydrgen bnds. The hydrgen bnds are again frmed between carbnyl xygens and amin hydrgens, but unlike α-helices, the residues may be separated by great distances n the plypeptide chain. The directin f the plypeptide chain is always determined frm the amin terminal and fllws the repeating pattern f - - (carbnyl) -- - (carbnyl) -- - (carbnyl). The sheets may be parallel r antiparallel depending n the directin f the chains invlved. 11-16
A parallel β-pleated sheet. te the chains invlved run in the same directin. Peptide hain Directin f peptide chain ydrgen Bnds arbxyl Terminal 3 Amin Terminal Peptide hain α carbn Directin f peptide chain An antiparallel β-pleated sheet. Directin f peptide chain 3 Directin f peptide chain The Tertiary Structure f Prteins The verall three-dimensinal shape that results frm attractive frces between amin acid side chains is referred t as a tertiary structure f prteins. Tertiary structures are the first frm f functinal prteins and are frmed by interacting secndary structures. 11-17
The Quaternary Structure f Prteins The highest level f prtein rganizatin is called the quaternary structure. It is frmed by interacting tertiary structures and it represents sme f the mst cmplex prteins knwn. Quaternary structures are typically cmpsed f tw r mre prtein subunits (tertiary structures). nprtein cmpnents may als be present. emglbin is a tetramer (fur subunits) cntaining tw cpies f ne plypeptide and tw cpies f anther: tw identical chains f 141 amin acid residues each (alpha) and tw identical chains f 146 residues each (beta). 11.14 Denaturatin f Prteins Denaturatin is the partial r cmplete disrganizatin f a prtein s characteristic three-dimensinal shape as a result f disruptin f its secndary, tertiary, and quaternary structural interactins. Denaturatin renders the prtein nnfunctinal and can be caused by a variety f factrs, ie; heat, acids, bases, rganic cmpunds, heavy metal in, and mechanical agitatin. 11.15 Prtein ydrlysis ur bdy s digestive system must break dwn prteins int amin acid units fr them t be absrbed frm the intestine int the bld. nce absrbed, amin acids can be used t synthesize the human prteins. The prcess f prtein digestin invlves hydrlysis reactins that are catalyzed by enzymes. acid r acid r prtein + 2 smaller peptides amin acids base base 11-18
mewrk Prblems 11.1 What are the prducts when the fllwing triglyceride underges sapnificatin with a? 2 --( 2 ) 12 3 --( 2 ) 14 3 2 --( 2 ) 7 = ( 2 ) 7 3 11.2 Write an equatin fr the full hydrgenatin f a triglyceride cntaining glycerl, leic acid, linleic acid, and palmitic acid. w many mles f 2 are required t cmpletely hydrgenate this triglyceride? 11.3 A drug called U486 has the fllwing structure: 3 3 3-3 U486 a. w is the structure f U486 similar t that f prgesterne? b. w d the tw structures differ? 11.4 Use the three-letter abbreviatin t name the amin acid(s) having a. An alchl functinal grup b. An acidic side grup c. An α-amin grup in a ring d. A benzene ring 11.5 The pi value fr amin acid cysteine is 5.1. Draw the structure f cysteine that predminates in slutin at each f the fllwing p values: 11-19
a. p < 1 b. p = 5.1 c. p > 12 11.6 There are a ttal f six different amin acid sequences fr a tripeptide cntaining ne mlecule each f alanine, leucine, and glutamic acid. Using three-letter abbreviatins fr the amin acids, draw the six pssible sequences f amin acids. 11.7 Suppse a sample f prtein is denatured and anther sample f the same prtein is cmpletely hydrlyzed. mpare the final prducts f these prcesses. 11-20