General Chemistry II
General Chemistry II CHM 204
Popular in Course
Popular in Chemistry
verified elite notetaker
This 0 page Class Notes was uploaded by Houston Kovacek on Sunday November 1, 2015. The Class Notes belongs to CHM 204 at Marshall University taught by Staff in Fall. Since its upload, it has received 11 views. For similar materials see /class/233288/chm-204-marshall-university in Chemistry at Marshall University.
Reviews for General Chemistry II
Report this Material
What is Karma?
Karma is the currency of StudySoup.
Date Created: 11/01/15
Chapter 14 Aldehydes and Ketones 141 Structures and Physical Properties of Aldehydes and Ketones Ketones and aldehydes are related in that they each possess a CO carbonyl group They differ in that the carbonyl carbon in ketones is bound to two carbon atoms RCOR while that in aldehydes is bound to at least one hydrogen H2CO and RCHO Thus aldehydes always place the carbonyl group on a terminal end carbon while the carbonyl group in ketones is always internal Some common examples include common name in parentheses O O K H H H methanal formaldehyde trans3phenyl2propenal cinnamaldehyde preservative oil of cinnamon 0 2K 0 Propanofle acetone 3methylcyclopentadecanone muscone all P011511 remOVer a component of one type of musk oil Simple aldehydes e g formaldehyde typically have an unpleasant irritating odor Aldehydes adjacent to a string of double bonds e g 3phenyl2propenal frequently have pleasant odors Other examples include the primary avoring agents in oil of bitter almond Ph CH0 and vanilla C6H3OHOCH3CHO As your book says simple ketones have distinctive odors similar to acetone that are typically not unpleasant in low doses Like aldehydes placing a collection of double bonds adjacent to a ketone carbonyl generally makes the substance more fragrant The primary avoring agent in oil of caraway is just a such a ketone oil of carraway Because the CO group is polar small aldehydes and ketones enjoy signi cant water solubility They are also quite soluble in typical organic solvents 142 Naming Aldehydes and Ketones Aldehydes The IUPAC names for aldehydes are obtained by using rules similar to those we ve seen for other functional groups eg 70H 1 Locate the longest carbon chain in the molecule that includes the aldehyde group Name it like an alkane except use the ending ml in place of 6 2 Number the carbonyl carbon 1 and name all other functional groups as you ve seen previously Since aldehydes are always terminal there is no need to number them Cl HO N0 W0 W0 propanal 2chlorobutanal 3hydr0Xypr0pana1 Common names occur frequently for aldehydes These fall into two broad classes The first type of name is derived from the name used for a common carboxylic acid The name of the carboxylic acid typically comes from a Latin origin For example formaldehyde CHZO is derived from formic acid HCOZH You may know of formic acid as the major component of an ant bite The bite stings because the ant has injected formic acid into some of your cells and the acid causes those cells to die or be damaged For a creature the same size as an ant the effect is devastating The beginning form in formaldehyde comes from the Latin word for ant formica Note this is the same word as is used for some synthetic countertops Formica tabletops are made of a polymer of formaldehyde with a second substance The other type of common name occurs in compounds such a avorants On the rst page of the notes the compound 3phenyl2propenal was presented In fact it is never called this Rather it goes by its common name cinnamaldehyde Chemical names derived from terms such as this are common for substances that had been identi ed before their structures could be determined Ketones V As usual nd the longest carbon chain that includes the carbonyl group Use the alkane name except drop the nal e and insert one Ketones except propanone and butanone must have a number to indicate the location of the carbonyl group 2 V Name other functional groups as usual 0 O l O I C1 0 J bma one 4chlorobutanone cyclohexanone 2pentanone An older way of naming ketones was to name the groups attached to the carbonyl then add the word ketone Thus butanone was methyl ethyl ketone and 2 pentanone was methyl propyl ketone Finally propanone is nearly always called acetone 143 Oxidation of Aldehydes and Ketones Your book begins this section discussing Tollens and Benedict s tests Both tests are commonly used in qualitative organic chemistry to detect the presence of aldehydes by converting them to the corresponding carboxylate anions however neither is a particularly practical way of making aldehydes on the large scale The major reason is cost and this can be seen in the use of silver and copper reagents respectively On the industrial scale when compounds are frequently made in thousand to million pound quantities the use of this much precious or semiprecious metal would be prohibitively expensive When all one is trying to do is nd out if you have some aldehyde present these are quick and cost effective methods of accomplishing this It is in this context that they are of value in a medical laboratory As your book notes this method is of great importance when checking urine for glucose since glucose exists in an equilibrium in which one of its forms is an aldehyde see p 7 of notes When the latter is found it means that the body is not properly metabolizing sugar and there is a real possibility of diabetes AgNH32 is a complex ion These are species in which a simple metal ion eg Ag binds to a lone pair of electrons on a second species called a M The bond is reasonably strong so the species behave as a single unit Formation of the diammine silverI complex is shown below Your book points out that Benedict s reagent is a complex between Cu2 and citrate ion H H Ag HNH gt H7N Ag NH H H H however the formula Cucitrate2 is undoubtedly wrong The correct structure is complicated These complexes are common in nature For example hemoglobin containing Fe3 and chlorophyll Mg2 are complex ions Many of the metals your body needs are used as complex ions in your body frequently by enzymes Heavy metal poisoning frequently occurs when the heavy metal e g lead Pb2 or mercury Hg2 replaces another metal ion e g Mg2 or Zn2 and thereby deactivates the enzyme This also explains why mercury and lead salts are much more dangerous than the metals As metals they don t form complex ions in the body Thus they must first be oxidized and that generally doesn t happen in your body Nonetheless the metals are still bad for your health for other reasons and shouldn t be ingested Large scale conversions of aldehydes to carboxylic acids frequently employ either potassium permanganate KMnO4 or chromic acid H2Cr04 as the oxidant The metal by products of this reaction are more readily recycled than either the Tollens or Benedict s reagents For example ll KMHO4 l CH3CH25CH CH3CH25COH 144 Reduction of Aldehydes and Ketones In reduction reactions of aldehydes and ketones we add hydrogen across the double bond That is a hydrogen atom will be added to each atom of the double bond converting the aldehyde or ketone into an alcohol We can add this hydrogen in one of two different ways The first is to split apart a hydrogen molecule and add the two product hydrogen atoms or to use a hydride donor followed by adding a proton H For industrial scale reductions of small aldehydes and ketones the former reactions are frequently employed Hydrogen is mixed with either an aldehyde or ketone in the presence of a metal catalyst usually nickel platinum or palladium Aldehydes reduce to lo alcohols and ketones to 2 alcohols and under extreme conditions not shown the hydroxy group can be removed altogether II H CH3CH2CH2CH CH3CH2CH2CH20H Chemical reductions employing hydride reagents such as NaBH4 and LiAlH4 are also common Each acts as a source of the H39 ion although this ion never actually exists freely in solution The reaction proceeds in two steps In the first the electrons on the negatively charged hydride ion attack the positive end of the CO dipole The source of H ions may be either a 3 262 OH L gt RR Hgt RR H R R V H H dilute acid or even water Reagents like NaBH4 and LiAlH4 could never survive most biological conditions and your body uses enzymes to accomplish the same reactions For example LiAlH4 frequently ignites on exposure to water In the human body the NADH unit serves as the hydride ion source NAD nicotinamide adenine dinucleotide and water as the H source But otherwise the mechanism of reaction is largely the same 145 Reactions of Aldehydes and Ketones with Alcohols We will discuss a few other reactions of aldehydes and ketones now The first is that with alcohols This reaction is unusual in that the products of these reactions are normally unstable We are interested in them because in one important biological case the synthesis of carbohydrates the products possess high stability In this reaction an alcohol molecule adds across the carbonyl double bond with the alcoholic hydrogen atom attaching to the carbonyl oxygen Ifyou look back in your notes you will see 539OH Q H l Q39R gt R H that this reaction resembles the addition of water to a CC double bond to form an alcohol Chapter 12 notes p 7 This molecule one in which the same carbon is bound to both an OH and an OR group is called a hemiacetal A nearly identical reaction takes place with ketones to yield a hemiketal The difference is that the hemiacetal carbon is also bound to an H atom while the hemiketal carbon is bound to an R group H H Q Q RH RR O O R R hemiacetal hemiketal In sugars the molecule has an aldehyde group at one end and an alcohol group on the other The chain that connects them is 5 or 6 carbons long Ifthe molecule does an intramolecular internal reaction of this type the resulting product is a 5 or 6membered ring Rings of this size are particularly stable and in the case of sugars can polymerize into carbohydrates in a way the straight chain molecules can t Even so individual sugar molecules exist in an equilibrium between the ringopen and ringclosed forms H O T HOTH CHZOH CHZOH H C OH H H 0 OH H 0 H OH H OH H HO C H HO H HO OH HO C H H OH H OH HZC XDglucose BDglucose OH Hemiacetals and hemiketals can react with another equivalent of alcohol to yield acetals and ketals respectively The net effect is to replace the alcoholic hydrogen on the former with the R group of the alcohol An acid catalyst and large excess of added alcohol are needed for this reaction to proceed A typical conversion of a hemiacetal to an acetal would proceed as follows H Rquot Q Q H4r catal st R H RquotOH ygt R H H20 0 03 R R In the presence of a large excess of water the reaction will run in reverse When comparable amounts of water and alcohol are present the reaction is an equilibrium This is how the cyclic hemiacetal form of D glucose polymerizes to form a carbohydrate chain Have you ever noticed that if you chew a piece of bread or a saltine cracker for a few seconds and then leave it in your mouth for a minute or so it begins to taste sweet This is the acid and water in your saliva breaking down the carbohydrates starch in bread to their component sugars In your stomach this reaction occurs more quickly because it is more acidic there stomach acid is approximately 01 M HCl The nal reaction of aldehydes and ketones we will consider is the aldol condensation This a reaction where an aldehyde or ketone reacts with itself with the help of a base OH39 catalyst CH 101 H OH39 2 CH3CH W CH3CHCH2CH The reaction takes several steps shown below As you can see the hydroxide ion used up in the first step is regenerated in the third 0 II II CH3CH OH gt 39CHZCH H20 0 0 39 II II I II CH3CH 39CHZCH gt CH3CHCH2CH 039 0 OH 0 I II I II CH3CHCH2CH H20 CH3CHCH2CH OH39 This reaction is important because it leads to the formation of a new carboncarbon single bond a process that is generally difficult to do in organic chemistry We will see this type of reaction again later when a biochemical reaction uses an enzyme in place of OH39 to accomplish the same synthetic goal January 5 2002 Chapter 24 The lecture notes for this chapter will be briefer than those of previous chapters More than in those chapters these notes are going to simply point out highlights that you should pay close attention to Finally the notes below will concentrate on the chemistry of the cell That is to say things such as molecular structure and reactivity 241 Heredity and the Cell This chapter will concern it self with two macromolecules polymers with attached nucleic acids deoxyribonucleic acid DNA and ribonucleic acid RNA The former contains all of the information necessary to create a living entity To put it most brie y one type of RNA is created directly from part of a DNA molecule and through a series of steps involving several types of RNA it creates enzymes These are the catalysts that cause nearly all of the reactions in a cell to occur 242 Structure of Nuclei Acids There are some terms and structures you will need to become familiar with First at a very basic level DNA and RNA share the same structure phosphate PemOSe sugar There are two significant structural differences between DNA and RNA The first is DNA employs deoxyribose in its backbone while RNA incorporates ribose into its background The second major difference is that for DNA the four pendant bases are adenine thymine guanine and cytosine while RNA substitutes uracil for thymine You aren t responsible for the structures of the individual bases but you should remember which bases are associated with which nucleic acid The base always attaches at the aldol carbon You should know the difference between ribose and deoxyribose These species are called nucleic acids because the phosphate groups have one 0H left after the backbone forms and this hydroxy group is acidic As you already know DNA consists of two strands wrapped around each other like braids called a double helix They are hooked together by pairs of bases hydrogen bonded to one another Figure 245 p 673 In particular it is worth remembering that each base can hydrogen bond effectively to only one other base thus they M appear paired along the double helix Guanine always pairs with cytosine CT and adenine always pairs with thymine DNA AT or uracil RNA AU Thus the strands are said to be complimentary One final note Since the bases along the strands each bind to its complement on the other strand one would be tempted to say this was the strongest interaction between the two strands In fact it is a hydrophobic interaction The bases are hydrophobic and turn inward to avoid water This gives rise to the twisting of the strands While your book doesn t say this my guess is that the complimentary bases come about for two reasons First is that it maximizes hydrogen bonding and hence stability of the double helix The second is that this mechanism results in a minimum of transcription errors and this is crucial to the health of an organism Finally one tends to think of the DNA as being one continuous string of useful information While this may well be true at the present time it appears that there are sections with no useful information that are place holders Some of this seems pretty logical You d expect a spacer between the code to make hemoglobin and the code to make collagen What s interesting is that there are spacers in the middle of the code to make nearly all proteins Why this is so is still a mystery 24 3 Ribonucleic Acids There are several different types of RNA and each has a unique function What is of primary importance to us here is how one creates a protein from a nucleic acid As we have already seen nucleic acids and proteins share no common elements This naturally gives rise to the question How can the former create the latter We begin with a basic bit of math There are twenty standard amino acids used to make proteins so the RNA must be able to select from among them at each linkage If only one base was necessary for the selection we could only choose between 4 amino acids one for each different base Iftwo consecutive bases along the backbone were used we could chose between a maximum of 16 amino acids there are 16 different pairings of the 4 bases AA AU AG AC UA UU the ordering of the pairs matters while 3 consecutive bases would allow for 64 different amino acids Since we only need 20 using 3 consecutive bases called an anticodon also provides for multiple combinations to signify the same amino acid A look at Table 241 p 681 shows that for many amino acids the identity of the third base doesn t affect the amino acid selected Thus an error at this site will not result in a defective protein This redundancy provides some genetic protection to us when proteins are synthesized A codon is similar to an anticodon except that it is used create the anticodon An anticodon is generated by determining the complimentary base for each base on the codon then listing them in reverse order Finally a protein is synthesized by taking the amino acids designated by the anticodon and polymerizing them into a single molecule in the order the anticodons appear on the transfer RNA The rest of this chapter is written such that I don t believe I can much to it here April 27 2002 Chapter 19 Lipids In the last chapter we looked at what constitutes the major energy source for most people We now turn to a group of compounds that is not only a major portion of our diet but also a major constituent of our own bodies Lipids include fats oils and cholesterol as well as other compounds that are less well known but very important for the operation of our bodies 191 What Lipids Are Lipids are a class of compounds that are de ned by how they are isolated rather than by their composition This makes them different from all of the other molecules we ve seen so far Until now all molecule types were de ned by functional groups Lipids are molecules that can be extracted from plants and animals by low polarity solvents such as ether chloroform or even acetone They are not appreciably soluble in water Fats and the fatty acids from which they are made belong to this group as do oils waxes and steroids Other classes of molecules belong to this class as we will see We now explore a number ofways to classify lipids Hydrolyzable lipids are those that contain a functional group that will react with water The functional group is usually an ester and the list of compounds includes neutral fats waxes phospholipids and 39J quotIf 39 lquot 39 39 39Vzable lipids lack such 3 quot 39 groups and include steroids and fatsoluble vitamins eg A D E and K Fats and oils are composed of triacylglycerols These are compounds prepared by the union of glycerol 123trihydroxypropane and 3 fatty acids to form a triester These are the neutral fats and a generic example is shown below HZC OER 0 II HC OCR 2 HZC OCRquot The old name for these molecules was triglycerides and that name is still used by physicians in blood tests Complete hydrolysis of triacylglycerols yields three fatty acids and a glycerol molecule Fatty acids are long chain carboxylic acids typically 16 or more carbon atoms which may or may not contain carboncarbon double bonds Fatty acids almost always contain an even number of carbon atoms and are usually unbranched Oleic acid CH3CH216C02H is the most abundant fatty acid in nature It is monounsaturated Those fatty acids with no carboncarbon double bonds are called saturated those with one double bond are monounsaturated and those with two or more double bonds are called pol gnsaturated Typically each triacylglycerol contains 3 fatty acids These fatty acids may be the same or different Saturated fats are typically solids and are derived from animals while unsaturated fats are liquids and usually extracted from plants In all unsaturated fats the double bond assumes a cis geometry This prevents the molecules from packing as efficiently as they do in saturated molecules and this causes the lower boiling points of unsaturated fats Fatty acids may also be classified as essential or nonessential Essential fatty acids are those that our bodies cannot synthesize and must be obtained from our diets Nonessential fatty acids are those that we can make in our bodies because we have the proper enzymes present Waxes are simple esters with very long hydrocarbon chains In Chapter 15 you learned that short chain esters frequently generated pleasant odors eg CH3CH22C02CH2CH3 pineapple One of the reasons they give a pleasant smell is that with short hydrocarbon chains they are slightly watersoluble so can be dispersed throughout fruits and vegetables and being small and lightweight they have high vapor pressures evaporate readily In contrast the wax CH3CH224C02CH229CH3 melissyl cerotate a major component of beeswax is a water insoluble solid at room temperature The chain including an ester oxygen is 57 atoms long For all intents and purposes this material is no more watersoluble than any alkane Lanolin is another wax In plants waxes cover the outside of fruits vegetables and leaves to prevent excessive loss of water and to protect against attack by parasites In animals waxes can make feathers water repellent or keep skin soft among other things Whale oil CH3CH214C02CH215CH3 cetyl palmitate was once used as fuel in oinments and cosmetics and in candles Its use has been banned since 1970 The first part of the compound name cetyl is derived from the biological order cetacz39a to which whales belong 192 Chemical Properties of Tliu 39 39 39 As was mentioned in the previous section hydrolysis of a triacylglycerol yields a glycerol molecule and 3 usually different fatty acid molecules Unlike the acids used by chemists to accomplish such a task the body employs the enzyme triacylglycerol lipase to catalyze the hydrolysis 9 9 HZC OCR HZC OH HOCR u 3H O triacylglycerol 9 HC OCR 2 gt1ipase HC OH HOCR O 9 H2COE39R HZC OH HOCRquot As you know our bodies retain fat as an energy storage mechanism not simply to deny us fun foods as we get older When a fat molecule is hydrolyzed some of that energy is released The three new OH bonds are stronger than the three CO bonds that are broken The difference in the bond strengths accounts for most of the energy released When fats are ingested the body cleaves off one or two of the acid groups in the intestines This is because fat molecules are too large to pass through cell membranes The monoacylglycerol or diacylglycerol and fatty acid then pass into the cell Later the molecules are recombined into fat molecules Fat molecules travel through the body by hitching a ride on proteins traveling in the bloodstream Soaps were discussed brie y in Chapter 15 pp 7 7 8 of the notes The reaction of sodium hydroxide with fat molecules releases glycerol and the sodium salts of the fatty acids RCOZNa No source I have found discussing the production of soap says that they are made from synthetic fatty acids Although none explicitly says that they are made by the saponification and further processing of animal fat it appears that that is how they are in fact made My guess is that soap manufacturers are trying to avoid grossing out their customers By now you have almost certainly seen the phrase partially hydrogenated vegetable oil in the ingredient list of some food What does it mean We learned in Chapter 12 that hydrogen could be added to alkenes carboncarbon double bonds to make alkanes This process is called hydrogenation As we learned a short time ago most vegetable oils contain very high percentages of unsaturated acids By hydrogenating some not all of the CC double bonds in the oil its melting point slowly rises until it becomes a solid at room temperature This is the major reason for making partially hydrogenated fats Solid fats are easier to store and many people prefer the texture and convenience of solids For example natural peanut butter or homemade stuff you can make yourself will separate with time When you open a bottle of natural peanut butter there will be a significant oil layer on top that must be stirred back in to soften it enough to spread on a piece of bread Wait a day or two and the oil begins to come out again Standard commercial brands remove some of the peanut oil partially hydrogenate it and then put it back This prevents separation and helps maintain texture In terms of caloric content all fats are the same 90 Calories per gram Because they are liquids and won t form solid deposits in your veins and arteries fats with very high percentages of monounsaturated and polyunsaturated fatty acids are healthier than those with high percentages of saturated fatty acids Partially hydrogenated vegetable oil differs from animal fat only in that it lacks cholesterol 193 Phospholipids There are two classes of phospholipids The first are the glycerophospholipids which are themselves subdivided into two groups The first group phosphatides is molecules composed of glycerol substituted with two fatty acid esters just like in fats and at the third position a phosphate unit connects to an alcohol You will see that the picture I ve drawn is different from that shown in your book p 557 in that this picture has charges on the phospho part of the molecule This is because Ihave found no examples of neutral phospholipids While they may well exist they are clearly not among the most important examples of this class of compounds 9 H2O OCR 9 HC OCRquot 9 H2O 0130R 0 Three alcohols that form phosphatides are choline ethanolamine and serine These compounds are important to the body and are transported as the following phosphatides The enzymes either cut the molecule free when it is needed or convert it to some other necessary material The phosphate group and the organic chain attached to it carry electrical charges All three phosphatides are components of cell membranes 0 II II II HZC OCR HZC OCR HZC OCR O l O 0 II II II HC OCR39 HC OCR39 HC OCR39 O 2 9 ll HZC OlIDOCHZCHzNCH33 HZC 01IDOCHZCHZNH3 HZC Oll30CH2IZHCOz O39 O39 O39 NH phosphatidylcholine phosphatidylethanolamine phosphatidylserine lecithin cephalin Choline is a watersoluble vitamin as recognized by the Food and Nutrition Board usually classi ed as a B vitamin used to make complex lipids Phosphatidylcholine is the principal phospholipid of cell membranes It is also converted to acetyl choline CH3C02CH2CH2NCH33 which is an important neurotransmitter it carries electrical charges from one nerve cell to another Choline helps break down homocysteine 7 a cardiovascular disease risk factor A lack of this vitamin leads to fatty livers andor hemorrhagic kidney disease Serine is the parent of a family of amino acids that also includes glycine and cysteine Enzymes convert serine as part of phosphatidylserine to glycine and cysteine Serine is also involved in the generation of ethanolamine which is in turn converted to choline Interestingly phosphatidylethanolamine is de cient in Alzheimer s patients They also act as a histamine blocker in the body The other subclass of glycerophospholipids are the plasmalogens These differ from triacylglycerols by even more than the phosphatides A generic plasmalogen would look like HZC OCHCHCH215CH3 note the ether linkage and adjacent CC double bond ll HC OCR Hzc Og OCHZCHZNR R H or CH3 0 The compound with R CH3 is called platelet activating factor It is a strong bronchoconstrictor It also stimulates other cells to increase their functional and metabolic activities The second major class of phospholipids are the sphingolipids Sphingolipids include the sphingomyelins and cerebrosides Both are based on the molecule sphingosine Sphingomyelins have the basic formula OH H39 CHCHCH212CH3 9 HC NHCR lt fatty acid this is the only group that can vary 0 HZC OP OCH2CH2NCH33 0 As the name suggests this lipid is affiliated with the myelin sheath surrounding the cells of the central nervous system Sphingomyelins comprise about 25 of the lipids in the myelin sheath and their role is key to brain function and electrical transmission through our nervous system The other type of sphingolipids we are concerned with are cerebrosides which are not phospholipids These compounds are again based on attachments to a sphingosine molecule a sugar OH I OH HC CHOCHCH212CH3 l CHZOH O I m H NHCR 4 fatty acid HO OH OCH2 Not surprisingly these molecules are called glycolipids cf glycosides are acetals of sugars Most of these molecules incorporate BDgalactose sugars Cerebrosides are found most commonly in cell membranes in the brain One cerebroside found outside the brain a glucocerebroside is found in the membranes of macrophages cells that destroy foreign microorganisms Several disorders are associated with malfunctioning of sphingolipid metabolism Probably the best known is TaySachs disease which strikes infants and is typically fatal by age 3 NiemannPick disease also strikes infants and is fatal early in life Gaucher s disease and Fabry s disease strike later in life and are generally less devastating 194 Steroids Steroids are nonhydrolyzable lipids All steroids contain the following fused ring system Like other fats these molecules have high molecular weights Several important ones are pictured on pp 55961 of your textbook Most have so few polar groups that they will have negligible water solubility Cortisol with two keto and 3 hydroxy groups is an exception having slight solubility in hot water Your book does a nice job describing several steroids and you should read about them Your book calls bile salts detergents that aid in the digestion and absorption of various lipids and fatty acids Why is the term detergent appropriate Ifyou didn t read the Interaction 194 on p 556 now is a good time Detergents belong to a class of molecules called surfactants for surfaceactive agents They are molecules with a very polar end typically an ionic group and a long nonpolar segment When placed in a polar environment as both Tide and bile are the polar end associates well with water The nonpolar tails will congregate together While this is an oversimplification you can think of these as forming a ball with the ionic groups forming the cover and the organic hydrophobic tails pointing in towards the center These structures are called micelles see Figure 192 p 562 of book for a representative picture When one of these micelles comes into contact with fats fatty acids fatsoluble vitamins etc the fat is drawn into the center of the micelle for transport to the intestinal wall At the wall the hydrophobic groups can interact with cell membranes which are themselves hydrophobic water avoiding in such a way as to allow the nutrient to pass into the intestinal cells We will return to this at the end of the chapter The only steroids discussed in the text are animal steroids and more speci cally ones found in humans Steroids also occur in plants and the cardiac steroids form an important class This might strike you as odd at first it certainly did me because plants don t have hearts One member of this family is digitoxin a powerful heart stimulant shown below It is somewhat O 0 digitoxin HO similar in composition to cholesterol and is used to treat congestive heart failure Needless to say too much of this steroid like all steroids is harmful and is potentially fatal Doses as low as 1 mg have a measurable effect on heart function Digitoxin is extracted from the foxglove plant digitalis purpurea 195 Cell 39 39 7 Their Lipid In several places in this section you have been told that suchandsuch compound is an important component of the membrane of some type of cell We will now discuss the construction of a cell membrane and will end the chapter discussing why this is both marvelous and fascinating at least to me Consider a generic phospholipid E O39 OCR O ROllioCH2 IEH CHz 05Rquot The phosphate end is charged and will have strong attractive interactions with water hydrophilic The rest of the molecule will except a minor dipolar interaction interact very poorly with water hydrophobic When this substance is added to water it will undergo self assembly to a larger structure By that we mean the molecules will all by themselves associate and form a larger structure This contrasts with adding acetic acid to water If you added one million acetic acid molecules to a liter of water and stirred what would happen Ifwe cut the liter in half we would expect to find 500000 acetic acid molecules in each 500 mL If we divided it into 1 mL samples we would expect each mL to have just about exactly 1000 acetic acid molecules Ifwe divided each mL into uL samples ll000000 L we would expect almost all to have 1 acetic acid molecule although some would have 2 and some 0 because of random motion The point here is that when the vast majority of substances are added to a solvent they dissolve and randomly distribute Ifwe added a substance that is completely insoluble in the solvent we expect the layers to stay completely separate Phospholipids are intermediate molecules however One part wants to go into solution the other part resists it The result is that the hydrophobic ends tend to congregate together and the hydrophilic ends do likewise but that isn t quite enough The natural shape for assembly is a sphere This maximizes hydrophobic interactions on the inside and hydrophilic interactions on the surface The result is the micelle shown in Figure 192 p 562 As with detergents molecules with little to no hydrophilic parts will be pulled into the micelle Needless to say this will cause the micelle to expand to accommodate the extra volume The result is that the micelle will become ovate oval shaped 63111 cholesterol le As more things are added the oval becomes longer and atter until it is essentially two layers This is called a lipid bilayer and is the basic construction of the cell membranes Thus molecules like cholesterol help to stabilize the cell membrane by keeping the membrane at Figures 193 and 194 p 563 show this progression The cell membrane also includes proteins that assist in moving things into or through the cell membrane We discuss them in the next chapter Cell membranes are selfsealing for the 12 same reason that they form in the first place Ifsomething displaces some of the molecules in a cell membrane intermolecular forces will push the hydrophilic and hydrophobic parts of each molecule back into place This brings us back to the first paragraph in this section In all general chemistry courses we teach and learn that covalent and ionic bonds are quite strong and that intermolecular forces are relatively weak Indeed London forces p 161 183 of your book are generally thought of as being very weak These forces are the ones operating between the tails in cell membranes Ion dipole forces and hydrogen bonding operate between the phosphate groups and water Yet we have just seen that cell membranes are not one giant molecule stretching around the cell but rather a large number of molecules only loosely associating Thus the cumulative effect of intermolecular forces in this arrangement is so strong that it not only permits single cell creatures to eXist but also us The cells in our bodies form from this aggregation of lipids and we too are held together by what we lea1n are only weak forces This is truly something at which to marvel March 16 2002 Chapter 20 Proteins The previous two chapters Carbohydrates and Lipids have dealt with substances with a primary mission to provide energy to the body Lipids are also the primary constituents of cell membranes In contrast although we can obtain energy from proteins this is not a major function they serve As a molecular class proteins and polypeptides the primary difference is molecular length are jackofalltrades molecules Each proteinp0lypeptidepeptide will have only one very specific function but those functions range from fighting infections to carrying oxygen through the blood to being the major constituent of hair We will begin by considering their chemical composition then proceed to an examination of their structure Along the way and at the end we will look at various proteins and the bodily functions they serve As a final note relatively few structures in this chapter are dealt with using their chemical structures For that reason you will need to have your book available as you read these notes I don t have the capability of drawing many of the structures you will see in this chapter 201 Amino Acids The Building Blocks of Proteins Proteins polypeptides and peptides are all composed of a string of ocamino acids As the name suggests amino acids are compounds that contain an amine group NH2 and an acid group COZH The 06 refers to the relative locations of these groups In ocamino acids the NH2 and C02H groups are attached to the same carbon In Bamino acids these groups are on adjacent carbon atoms and in y amino acids there is a carbon between the carbons to which they are attached An interesting and important structural feature of amino acids is that the acid group on the molecule transfers its proton to the base group Thus although the molecule remains electrically neutral it has two charged groups within it The following pictures show 06 5 and y amino acids H 0 I II II II H3No0039 H3NCH2CH2CO39 H3NCH2CH2CH2CO39 substituent ocamino acids Bamino acids y amino acids Only ocamino acids appear in proteins polypeptides and peptides so we will only discuss those in the future Substituents can replace a carbonbound hydrogen in B and y amino acids For that reason unless otherwise stated assume that the term amino acid refers to Xamino acid The amino acids that comprise proteins and peptides come from the consumption eating of proteins and peptides and from production within our bodies Those amino acids that our bodies cannot produce are called essential amino acids while those that it can are called nonessential In the typical diet meats provide these materials although certain plants particularly beans provide can substitute for meat When we eat meat our body breaks the protein down into its constituent amino acids then reassembles them into ones our body uses Since we are animals too the ratio of different amino acids in our diets is similar to those we need The result is that a diet that includes meat provides us with our amino acid needs without effort Ifone chooses a vegetarian diet one must be careful in selecting protein sources The amino acids appearing in plant proteins typically occur in different ratios from our bodily needs Complicating a vegetarian diet is the fact that our body cannot store amino acids Excess amino acids are either burned for fuel or excreted This means that vegetarians must blend protein sources from different plants on a regular basis This is not as big an inconvenience as one might imagine Just like you don t need to eat meat at each meal one doesn t need to get the protein balance just right at each meal Furthermore dairy products can provide an animal based protein source Around the world most people live on diets that are completely vegetarian or very nearly so for economic reasons In these cultures speci c food combinations generate the right balance of amino acids Two such combinations are tofurice and tortillarefried beans When your body digests protein all the amino acids it uses to recreate peptides and proteins fall into a group of 20 amino acids called the standard amino acids A table listing them is provided on p 569 of your textbook Other amino acids appear in proteins and peptides in your body but all of these are derived from a standard amino acid That is once a standard amino acid is incorporated into a peptide or protein it is altered to a different amino acid We ll return to this later in the notes We now need to discuss some properties of amino acids As you know amines are weak bases and carboxylic acids are weak acids When amino acids form the carboxylic acid proton is transferred to the amine group A molecule 39 39 both a p itiv l and quot 39J charged group is called a zwitterion The pH of this solution depends on how strong the acid and base are relative to one another If the acid was stronger the pH will be less than 7 while if the base were stronger the pH would climb to above 7 Can you gure out how changing the substituent would cause the relative strengths of the acid and base to change That amino acids exist as zwitterions affects their properties For example if glycine existed as H2NCH2C02H do you think it would be a solid liquid or gas It would probably be a liquid Propionic acid CH3CH2C02H is a liquid and weighs just a little more Butyl amine CH3CH2CH2NH2 weighs a bit less and is also liquid Thus the fact that all standard ocamino acids are solids is a function of their existence as zwitterions Iftwo electrodes are placed in a solution of sodium chloride and one is charged positively anode see p 204 of your textbook and the other negatively cathode the sodium ions will be drawn to the cathode and the chloride ions to the anode This is true of any ionic species What about the zwitterionic amino acids Since each molecule of an amino acid is electrically neutral the positive and negative charges offset none will be drawn preferentially towards either electrode This pH is called the isoelectric point pI Ifwe lower the pH below pI then there are excess protons available to add to the weak base C0239 H I ll I ll H3NClCO H H3N9COH substituent substituent The product molecule is no longer electrically neutral and would be drawn towards the cathode In very highly acidic solutions only the ion on the right would exist but typical biological solutions e g blood never become very acidic or basic vide infra So that as solutions become more acidic than pI an equilibrium exists between the two species Ifthe pH of a solution is raised above the pI a proton is removed from the weak acid NH3 H H3N c b039 B HZN c EO39 HB substituent substituent Again the product carries an electrical charge and in this case is pulled to the anode In biological uids the pH will never be so basic as to drive the reaction all the way to the right so the reaction will exist as an equilibrium in most situations At the pI almost every molecule is electrically neutral no excess or de ciency of Hf This is because at the pI both of the equilibria just described operate Thus while the large majority of amino acid molecules exist as the zwitterion small but equal amounts exist as the protonated and deprotonated forms We ll return to this topic in Section 203 There are a number of ways to classify the side chains substituents One way is to group them according to their interaction with water ie solubility Nonpolar side chains include all of those in the first group in Table 201 p 569 textbook and methionine from the sulfur side chains group at the bottom of the table These hydrophobic side chains interact poorly with water Almost half 9 of the amino acids contain nonpolar side chains A second group includes polar side chains Some are neutral ie not acidic or basic These molecules include all of the side chains with alcohols and amides Cysteine is frequently included with this group although sometimes it is placed in the nonpolar group Others incorporate acidic and basic side chains These amino acids include an extra carboxylic acid or amine group respectively Summarizing nonpolar 7 alanine valine leucine isoleucine phenylalanine tryptophan proline methionine polar neutral 7 glycine serine threonine tyrosine asparagine glutamine cysteine polar acidic 7 aspartic acid glutamic acid polar basic 7 lysine arginine histidine Cysteine has the special property of being able to form a disulfide linkage In Chapter 13 Section 6 p 12 notes p 420 textbook we learned that thiols readily oxidize to disulfides When amino acids with nonpolar side chains are dissolved in water they tend to associate with the nonpolar side chains grouping together somewhat like a micelle p 9 Chapter 19 notes These interactions are usually weak and therefore uid A disulfide linkage is a covalent bond and hence much stronger Thus disulfide linkages have a prominent role in maintaining the threedimensional structure of proteins Finally all but one standard amino acid is optically active Look at table 201 and try to figure out which one isn t The requirement for a molecule to be optically active is for it to have a chiral center and that usually requires four different groups bound to a tetrahedral carbon Glycine has two hydrogens bound to the 1 carbon and that is the only tetrahedral center in the molecule so glycine is achiral Almost all naturally occurring amino acids are Lamino acids 202 Overview of Protein Structure All proteins have 3 levels of structure some have 4 As we shall see peptides will generally have only one or two levels of structure Level 1 structure is simply the sequence of attached amino acids in the chain remember proteins are amino acid polymers Level 2 structure short range results from the interactions between small groups of amino acids along the chain Level 3 structure longrange results from the interactions between level 2 structures Level 4 structure results from 2 separate protein chains interacting Thus for proteins that function in the absence of other proteins this level of structure is missing 203 Prima Structures of Proteins To generate a polymer we must first see how the amino acids combine to form a larger structure Reaction of the amine end of one amino acid with the acid end of a second amino acid yields a special type of amide bond called a peptide bond A molecule containing only two peptide bond 0 r H o Ill 9 Ill 9 Ill II I II H3NIDCO39 H3NIZCO39 m H3NIDC NHCCO39 H20 substituent l substituent 2 subst l subst 2 amino acids linked by an amide bond is called a dipeptide A natural question that follows from this picture is Can the peptide form in the other direction ie H O H O I ll I ll enzymes I I ll H3NCCO H3NIECO H3NCC NHIZCO H20 substitluent 1 substituent 2 sublst 2 subst 1 As you might have expected the answer is yes although a different set of enzymes must catalyze the reaction After amino acids have combined to form part of a peptide they are referred to as amino acid residues We now need to go over a few definitions Peptides polypeptides and proteins differ in that they contain different numbers of amino acids in their primary structure chain A peptide is composed of 2 7 10 amino acids while a polypeptide ranges from 10 7 50 Fifty or more amino acids make up proteins Please remember these are not hardandfast numbers except the lower limit of 2 for peptides Different individuals use different ranges Enzymes construct peptides polypeptides and proteins Consider glycine and alanine An enzyme that begins a peptide glycinealanine is incapable of generating the reverse combination at the beginning It is this property that allows the body to construct very specific amino acid sequences from the standard amino acids This specificity is required because the 20 standard amino acids can generate almost 400 different dipeptides 202 and almost 8000 tripeptides 203 The number of possible combinations for a protein is mindboggling A single enzyme cannot generate an entire protein but it will produce peptides that other enzymes will combine into polypeptides and still others will construct the protein To simplify writing out peptideprotein amino acid sequences 3letter abbreviations are used for each amino acid Thus glycylalanine shortens to glyala Like all polymers peptides and proteins have a backbone that runs the length of the molecule The polymers discussed in Chapter 12 p 10 notes all had a carbon backbone with all CC single bonds Proteins have a more elaborate backbone because of the presence of peptide amide bonds Their backbone looks like R Ill 0 N H3N W N NO 0 0 substituent H Adding an amino acid to the end of the existing peptide expands the peptide By convention for amino acids through proteins the amine part is written to the left and the carboxylate group to the right Just like the parent amino acids peptides and proteins exist as zwitterions And just like amino acids proteins have isoelectric points However there is an important difference While amino acids are not in nitely water soluble under standard biological conditions they do not become insoluble In general as molecules become larger they become less soluble Thus all other things equal proteins will be less soluble than the amino acids from which they are formed You were told in Section 201 p 6 that the solubility decrease for amino acids at the pI was not of major signi cance but it is for proteins At the pI of a protein its solubility is at a minimum and many proteins can precipitate from solution become largely insoluble This is why understanding pH is so important in the life sciences Ifthe pH of a biological solution e g blood strays too far from its normal value proteins may begin to precipitate and this may cause cell or even organism death 204 Seconda Structures of Proteins Now that we have the sequence of amino acids that make up a protein what does it tell us about the 3dimensional molecular structure On the surface not much but if we look deeper the information is there To begin answering this question let s look at the groups that make up the protein backbone In particular pay attention to the atoms bonds and electrons highlighted in blue and green H3N O39 In CHM 203 you learned that the angles made by hydrogen around ammonia are approximately tetrahedral 1095 p 106 textbook the same is true of organic amines But the angles around amides are much closer to 1200 than 10950 Why In Chapter 12 p 4 notes you learned that double bonds resulted from a standard single bond plus the sidetoside overlap of 2 porbitals If instead of placing the lone pair of electrons in an orbital like the ones it uses to bond to its neighbors the electrons go into a porbital that orbital can overlap the porbital on carbonyl carbon just like the porbital on the oxygen can This is very similar to the way bonding happens in benzene p 13 Chapter 12 notes O Nquotquot39IIIII X 200 E 6 R H When this happens it is not possible for the molecule to twist around the CON bond like it can the CsubstituentN bond The result is that all of the atoms and bonds colored green lie in the same plane as do all of the atoms and bonds in blue Because each plane can rotate around the carbonRquot bond these planes will rarely be parallel coplanar Because bond rotation can occur at only every third atom this backbone is fairly rigid and this has important structural implications as we shall soon see All peptides have many groups capable of hydrogen bonding Each hydrogen bound to nitrogen can hydrogen bond to a carbonyl oxygen either in an adjacent chain or if the backbone curls around on itself to a carbonyl oxygen further down the chain Both kinds of associations occur Thus two out of every three backbone positions are indirectly available for hydrogen bonding The third position always carries a substituent Whether the substituent can hydrogen bond or not affects protein structure Recall that substituents fall into one of two categories polar or nonpolar All of the polar substituents can hydrogen bond while none of the nonpolar substituents can Without getting into detail here peptide and protein strands will twist and or align to group the nonpolar substituents together An isolated nonpolar substituent can disrupt a sequence of twists In short switching between polar and nonpolar groups and even different groups within a category because of different sizes and shapes will disrupt coils and sideby side associations This contributes to the 3dimensional structure of a protein The two most common secondary structures are the Xhelix and Bpleated sheet We begin with the former You have of course heard of the double helix associated with DNA and we will examine that in the final chapter The shape of the Xhelix is related to it It takes 36 amino acid residues to complete a single turn of an Xhelix Thus each amino acid residue hydrogen bonds to another amino acid residue 4 residues before and 4 residues after it in the coil The length of one coil is about 54 nm for comparison one carbon atom diameter and a CC single bond are each about 015 nm The hydrogen bonds between the amide hydrogens and the carbonyl oxygens are parallel to the length of the coil In an Xhelix all substituent groups point outward Your book shows an Xhelix on p 579 As with all secondary structures some R groups are poorly compatible with the Xhelix For example glycine tends to make the coil too exible very small R while proline tends to make it too rigid including the amine N in the R group makes it too rigid Likewise acid groups and large groups tend to disrupt the coils This is not to say that these groups M be absent only that they cannot appear frequently in an Xhelix ocKeratin is a protein that makes up hair nails and hooves of most land animals One of the distinctions of the particular Xkeratin that makes up human hair is that the only secondary 11 structure that appears is the Xhelix It is important to remember that these secondary structures generally do not involve large numbers of amino acid residues Your book tells us that 11 residues are common roughly 3 full turns around the coil and that 53 residues are the maximum 14 turns The point is that in any protein we can expect to see several different coils andor other secondary structures present Thus in the example of human hair Xhelices generally come in groups of 3 We shall soon see that this group of 3 helices makes up a tertiary structure ocKeratin is discussed in more detail on pp 2021 The second major secondary structure in proteins is the Bpleated sheet Let s go back to the picture of the protein highlighted in blue and green on p 8 of these notes Looked at in the proper orientation the planes intersect to form a Vshape In the picture shown below the blue and green lines represent the planes from the earlier structure planes perpendicular to the plane of the paper Ellquot RH Ifarranged properly the following arrangement occurs R H 5 lt sideview topView gt g RH omitted H R for clarity IT where the blue zigzag line represents carbonylamide planes perpendicular to the plane of the paper You might call this a pleated strand A pleated sheet arises when several pleated strands line up sidebyside and add depth to the structure A pleated strand will incorporate 6 7 15 amino acid residues while a sheet will be made of 2 7 15 pleated strands BPleated sheets are held together by hydrogen bonds just like Xhelices You can make a similar structure with a sheet of paper by folding it at oneinch intervals accordion style When unfolded you can see the origin of the name pleated sheet At each ridge maximum and minimum lies a pivoting carbon to which R and H bind Along a top ridge these groups point up and along the ridge while at the bottom they point down and along the ridge Flexible lengths of amino acid residues permit the strands to wrap around and align next to each other connecting into pleated strands The strands can either align in the same or opposite directions In general those with amino acid residues occurring in opposite sequences proceeding in the opposite direction are somewhat more stable than those with the same residues lined up sidebyside Your book has a nice picture Figure 206 p 580 that shows how these two patterns of alignment can occur 205 Tertiary Structures of Proteins The actual 3dimensional shape of an entire protein is its tertia structure Why make a fuss over this After all all molecules have a 3dimensional shape don t they The answer to this question as you have already guessed is not usually Some molecules like benzene have their atoms locked into place e g by double bonds and so have an enforced structure Most molecules have many atoms with tetrahedral geometries that can rotate freely For example a molecule as simple as butane has two predominant rotational arrangements while pentane has 4 In each case the presence of multiple structures arises because there is free rotation about the C C single bonds Thus in most molecules there is no fixed shape As we have learned proteins contain at least dozens of amino acid residues and each residue contains usually two or more tetrahedral carbon So why do these molecules have only one structure When secondary structures form there are consequences beyond generation of that structural unit For example when an Xhelix forms the R groups bound to the tetrahedral 06 carbon point out from the spiral Ifthe R groups are hydrophobic water will bind poorly to it causing the protein to coil in such a way as to keep water away from this region Ifthe groups are hydrophilic the protein may open up to allow water in or it may twist to increase intramolecular hydrogen bonding The point of this discussion is that each secondary structure affects the environment around it and the protein as a whole will rearrange to maximize interactions that stabilize it This larger structure is held together in a number of ways 1 Hydrophobic groups tend to cluster together 2 Disulfide linkages form to provide the strength of covalent bonds between various structures These bridges are generically called crosslinks 3 Ionic interactions between side chain ionic groups C0239 and NH3 provide ionic bonds between different regions of the protein backbone These ionic interactions are sometimes called salt bridges 4 Hydrogen bonding between amino acid residues Another tertiary structural feature warrants comment Proteins frequently require the incorporation of one or more additional organic groups that are not amino acid based into their structures These groups are called prosthetics and frequently are the groups that actually accomplish the function associated with that protein Your book discusses the heme group in myoglobin When the heme group Figure 207b includes an Fe2 ion the protein acts as an oxygen storage unit In hemoglobin this unit causes the protein to be an oxygen carrier Some other examples include m Prosthetic group Function casein phosphate ester milk protein immunoglobulin saccharide antibody 5 different types A D E G M RNAbound protein nucleic acid protein synthesis in ribosomes see Chapter 24 206 Quaterna Structures of Proteins Quaternary structures arise when two or more polypeptides or proteins assemble into a larger structure In this structure they retain their separate identities Each polypeptide is called a m The subunits are held in place by the same 4 forces that operate in generating tertiary structures You should read the discussion of collagen in your book as an example of a quaternary structure We will see in the next section the consequences of altering a protein s shape and how easy it is to do so Hemoglobin is a quaternary structure consisting of 4 different proteins 207 Common Properties of Proteins As you have seen proteins carry out a wide variety of functions in the body It is interesting that despite this proteins behave in chemically similar ways This is because they are composed of similar perhaps the same amino acid residues and are strung together using the same peptide linkages The most severe thing that can be done to a protein is hydrolysis occurring as digestion In this process your body releases enzymes into the digestive tract that break the peptide bonds to form individual amino acids These are then absorbed into the body for reassembly into proteins it can use In a similar way enzymes in your body can break proteins down into amino acids for repair of damaged proteins or conversion of one protein into another Under ordinary conditions the damage to a protein is most likely to occur through denaturing Denaturing is the disruption of the shape organization of a protein in its naturally occurring state called the native protein Generally speaking disrupting any signi cant part of the secondary tertiary or quaternary shape may result in protein denaturation Denaturing a protein is bad because it renders the protein inactive at best What s worse is that under normal biological conditions denaturation is not routinely reversible Many things will denature a protein although only a few of them are problems under normal biological conditions Table 202 lists the major ways to denature a protein Of these heat as in frying boiling microwave radiation violent mechanical agitation soaps and the addition of organic solvents do not normally occur in living beings And as any lobster will tell you protein denaturation is the least of its problems when dropped into boiling water The other problems UV radiation adding strong acidsbases adding heavy metal ions and altering the ionic concentration of the bodily uid not listed in your book are all problems that can occur in real living systems Let s examine them individually UV radiation is only a problem near your body s skin UV light can penetrate the skin and can conceivably denature proteins in cells at or very near the surface of your body The power of UV radiation to affect molecules is demonstrated by causing both suntans and sunburns in the short term and it can lead to skin cancer over the long term Exposure to UV light also causes cataracts While strong acids and bases are not normally a problem for people or animals managing the pH of your bodily uids is of utmost importance For example your blood has a slightly basic pH 735 and changes of more than 02 7 03 units from that value can be fatal Since your bloodstream is a closed system under nonbleeding conditions it might seem as if this were a minor point Not so A waste product of energy production is carbon dioxide C02 and you may recall from CHM 203 Chapter 8 p 211 that it reacts with water to form carbonic acid H2CO3 C02 g H20 H2CO3 aq The pH of a saturated carbonic acid solution is about 38 far lower than that of blood The result of a failure of the body s system of removing C02 would be the rapid lowering of blood pH and the concomitant denaturing of blood borne proteins Shortly thereafter death would likely result That this is valid may be shown by C02 re extinguishing systems In remote unmanned chemical storehouses automatic C02 re extinguishers work by rapidly lt 30 seconds replacing all of the air with C02 Within a minute even if one tries to hold one s breath unconsciousness and death follow C02 release Another way to denature proteins is by heavy metal poisoning Metal ions generally from the second and third transition series e g Pb2 Hg2 Cd2 tend to bind strongly to the sulfur atoms in cysteine These links either result in the protein precipitating from solution or the generation of multiple metalS links that alter the protein con guration The nal real world way you can denature your proteins is by altering the ionic balance of bodily uids This is similar to pH changes in that a crucial regulatory system in your body must break down Denaturing occurs here because the change in ionic balance changes ionic bonding between amino acid residues and alters patterns of hydrogen bonding Each results in a modi ed protein 3dimensional geometry The devastating effects caused by only a small amount of altered proteins is demonstrated by prions Prions are a class of infectious agents that has only recently been recognized 1982 Dr Stanley Prusiner Univ of Calif School of Medicine at San Francisco The word prion is derived from the phrase proteinaceous infectious particle It is different from all other infecting agents because it has no nuclear material of the biological type It appears that prions work by infecting a cell and inducing other proteins to alter their shapes Once altered the protein ceases to perform its normal function and may engage in harmful activity Several diseases are now recognized as originating from a prion infection They include CreutzfeldtJakob disease kuru GerstmannStrausslerScheinker disease and the socalled mad cow disease Each exhibits very similar symptoms Both kuru and mad cow disease have been established as resulting from the consumption of contaminated meat human and beef respectively CreutzfeldtJakob disease has been accidentally transmitted by corneal transplants and human growth hormone therapy As stated in Section 203 changing the pH of a solution to the pI of a protein will result in its precipitation Thus even if the pH change doesn t denature a particular protein it may be removed from solution The result is essentially the same thing as denaturing the absence of a protein that is necessary for life functions 208 Cell quot RevisitediC39 39 C In Chapter 19 we learned that cell membranes were made up mostly of lipids fatty acids and steroids but also had protein components that allow material to be transported into and out of the cell All cell membrane proteins are glycoproteins That is all of these proteins contain a sugar molecule oligosaccharide as a prosthetic group As you might expect the sugar joins to the protein through the acetal 70H group It always joins to the protein at the terminal ammonium position instead of the C0239 terminus Furthermore the number 2 carbon is always substituted either with an amine amide or sulfate group Representative examples include CHZOH o CHZOH o CHZOH o I I I I I I H O ONCCHZ H O ONCCHZ H O ONCCHZ I I I H H H H H H OH H OH H OH H RO H RO H RO H H NH2 H NHgCH3 H s05 O When a substance is added to a normal uid eg water there are regions of high concentration and zero concentration at the beginning but over time the concentration of the substance becomes equal everywhere Consider a cup of hot water Ifyou dunk a tea bag in it there will be a brown splotch where the bag went in and out Even if you don t stir the tea after a while the water will develop a uniform light brown color as the tea diffuses through the cup In nature the equalizing of such concentration gradients occurs spontaneously ie without outside intervention In cells this natural diffusion is deadly We have larger concentrations of some ions in our cells than outside eg in blood and lower concentrations of others For the cell to function properly it must have a system whereby the proper concentrations of all ions are maintained ie sustaining a concentration gradient One such concentration gradient in the body relates to sodium Na and potassium K ions Your body maintains a higher concentration of sodium ions in the blood than in cells The reverse is true of potassium ions This protein compleX called the sodiumpotassium pump moves potassium ions into cells and sodium ions out of them to maintain the proper balance Proteins of this type were described brie y in the last chapter Another type of protein extends from the interior of one cell through its membrane and the membrane of a neighboring cell into the second cell s interior This type of protein is called a gap junction and it allows the transport of materials from one cell directly to another These proteins are necessary because not all cells are directly adjacent to blood vessels and a means of supplying nutrients and removing waste products is necessary Your book discusses these molecules in some greater detail A third type of protein acts as a w for molecules outside the cell The receptor binds molecules with only a very speci c shape e g hormones The binding alters the protein in such a way as to cause the part inside the cell to generate a physiological change One example of such a protein is the one that binds insulin On binding insulin the protein initiates a series of changes that result in the cell bringing in glucose Some receptors in the brain bind enkephalins molecules which on binding appear to block pain sensation Heroin and morphine activate these receptors All along we have been telling you that proteins bind only a certain shape Drugs and diseases sometimes work by mimicking that shape You would think or at least I would that the part involved in binding would have to be essentially identical to the natural binding agent Differences could occur further away but not really close to the binding site If you assumed this you too would be wrong Below are the structures of methionine enkaphalin and morphine both activate the same protein Apparently the pocket ts morphine and heroin just right Heroin looks just like morphine except the 0H groups are replaced by 70COCH3 groups N 9H 9H 9H 9H H3N l C N E C N E C N E C N f COZ CH2 5 HO O OH OH methionine enkephalin tryglyglyphemet morphine 20 The primary difference between morphine and heroin and enkephalins is that when the latter binds to a receptors cell the body rapidly sends an enzyme to hydrolyze the polypeptide so that its effect is short lived The body has no way to breakup a morphine or heroin molecule so their effects last much longer Without going into detail the addiction associated with these drugs is caused by the longterm attachment of the drug to the receptor This causes a prolonged suppression of a compound that tells the body there is pain somewhere Increasing dosages increase the suppression When the drug is removed the cells in the body enter a hyper mode r J this pain 39 J39 quot r J to get levels up to where they should be Unfortunately the body has gets accustomed to the lower level and then it reacts as if there is pain everywhere This is commonly called withdrawal 209 Classes of Proteins Two ways proteins may be classified are by solubility and function Within the solubility category there are subcategories that describe either a second physical property or a function Fibrous proteins are water insoluble They include the collagens elastins keratins myosins and fibrin Globular proteins are watersoluble and include the globulins and albumins The name of each category tells you something important about each classes physical shape Two globular proteins are hemoglobin and myoglobin The latter is discussed brie y in your book One fibrous protein is Xkeratin there are two types Each protein molecule is an extended XheliX because it employs no amino acids that disrupt the formation of Xhelices Furthermore because it projects all of its hydrophobic groups outward its quaternary structure is that of a pair of intertwined Xhelices a double helix A hair is composed of a collection of these pairs 21 coiling around one another in a superhelix The helices within the superhelix are held together by hydrogen bonding and disulfide bridges The way the hair treatment called a perm works is the hair is rst treated with a reducing agent to break the disulfide bonds then it is curled into the desired shape then an oxidant is added to reestablish the disulfide bonds The treated hair is thereby held permanently in the determined shape The perm is lost because the treatment doesn t alter how the hair is grown Collagen 20 types has a similar structure to keratin except that it exists as a triple helix This is the most abundant protein found in vertebrate animals and is found in teeth nails bone skin and tendons In teeth and bones the collagen is strengthened by the incorporation of inorganic materials such as hydroxyapatite polymer Ca5PO43OHX Collagen is discussed in your book on p 583 in some detail Nine categories of protein functionality are enzymes contractile tissue hormones neurotransmitters toxins and storage transport structural and protective proteins Examples of each are provided in the book on pp 596597 March 24 2002