What should you know in this chapter? Recognize the structure and properties of functional groups (e.g.

an -OH gives a molecule polor properties, -CH3 groups make it non polar, -COOH groups make a molecule acidic etc.); what is the importance of condensation reaction and hydrolysis; what are enantiomers, what makes a molecule optically active; sugars : aldoses have -OH groups and a -CHO , ketoses have -OH groups and a -CO group; recognize the cyclic structure of glucose; how does galactose and mannose differ from glucose, why is glucose the most abundant sugar; know some disaccharides ( table sugar or sucrose consists of a glucose bonded to fructose; know the structural difference between starch, glycogen, cellulose; know the names of some polar, non polar, ionic and aromatic amino acids; know the basic structure of an amino acids, what is the amino acid residue; know the different levels of protein structure and the molecular / atomic interactions which stabilize the structure; properties and function of proteins; recognize the fundamental difference of lipids compared to other biol. molecules (lipids are mostly non polar molecules); basic structure, properties and function of phospho - and glycolipids ( e.g. phospholipids: fatty acids, glycerol, phosphate and a polar alcohol) ; significance of cis and trans fatty acids; what are triglycerides ( know structural difference to phospho-, glycolipids), why do phospholipids form bilayers ?; Functional Groups The major elements found in biological molecules are carbon, hydrogen, oxygen, nitrogen, sulfur and phoshorous. Carbon can bind in covalent bonds to all of these atoms. In addition long chains of carbon atoms can be formed yielding structures which are common in living systems. Most biological molecules have so called functional groups. These are groups of atom that exhibit always the same chemical properties. The -OH group, -SH group, carbonyl group (-CO-), aldehyde group (-CHO) and amide function (H2N-CO-) increase always the polarity of a molecule. Ionizing functions, which make molecules very polar include -COO- ( -COOH ), -NH3+ ( -NH2 ) and under certain circumstances also -OH. Aliphatic groups such as -CH3 or CH3-CH2 and aromatic groups increase the hydrophobicity of a molecule i.e. they make it less polar. Some groups are chemically not stable. For example the aldehyde function ( -CHO) is easily oxidized to the carboxylic group (-COOH) or reduced to an alcohol group (-CH2OH). The -SH group is also oxidizable to -S-S- , a reaction which is very important in the folding of proteins. Condensation reactions All biopolymers are formed from monomeric molecules, in reactions that eliminate water. Functional groups, such as OH, COOH and NH2 are envolved in the reaction. For example: lipids are formed in a condensation reaction between an alcohol (glycerol) and fatty acids : R-COOH + HO-R' react to R-CO-OR' (ester) + H2O Nucleic acids are formed in a condensation reaction of the alcoholic OH groups of ribose and phosphoric acid to form phosphodiester bonds , which are the backbone of DNA and RNA chains. Ribose-OH + HOPO-(OH)2 react to Ribose-O-PO-(OH)2 + H2O Ribose-OH + HO-PO(OH)-O-Ribose react to Ribose-O-PO(OH)-O-Ribose + H2O In a similar reaction phospholipids are formed. Amino acids which have NH2 groups and COOH groups react with each other to form proteins (R is a residue or substituent group): H2N-CHR-COOH + H2N-CHR'-COOH react to H2N-CHR-CO-NH-CHR'-COOH + H2O The bond formed is a peptide bond. The reverse reaction is called hydrolysis, it means biopolymers are easily degraded into monomeric biomolecules by addion of water. Man made polymers are not made in a condensation reaction, thus, addition of water will not degrade them. Carbohydrates Carbohydrates are compounds which consist of carbon, hydrogen and oxygen. A common form of carbohydrates are the monosaccharides which have between 3 to 7 carbon atoms and a summary formula of CH2O. The simplest monosaccharide (or sugar) is glyceraldehyde The molecule has two types of functional groups: -OH and -CHO. The center carbon atom has three different substituents or groups attached to it and thus exhibits a molecular asymmetry known as optical activity . The structure with the OH pointing out of the plane is assigned the letter D (dextrorotary). The + sign indicates that the compound causes the plane of polarized light to be turned to the right. L(-) glyceraldehyde ( L for levorotary) which has its OH group pointing into the plane is the other optical isomer or enantiomer of glyceraldehyde and it rotates the plane of polarized light to the left (- sign). As seen above the two enantiomers are not superimposable, eventhough their chemical composition is identical. Glyceraldehyde plays an important role in the energy metabolism of the cell and is also an important intermediate in the synthesis of cellular compounds. The most abundant monosaccharides are pentoses (sugar s with 5 carbon atoms) and hexoses (sugars with 6 carbon atoms).

Hexoses Hexoses can have two different types of structures, aldoses and ketoses. Aldoses are sugars which possess one aldehyde group ( -CHO ) and several OH groups. The most common aldohexose is glucose. D-Glucose, when dissolved in water undergoes a chemical reaction to form two cyclic compounds known as alpha D-glucopyranose (OH in position 1 points down) and beta Dglucopyranose (OH in position 1 points out of the plane of the ring). In this structure all bulky residues (-OH and CH 2OH) point away from the ring (equatorial position), representing the thermodynamically most stable conformation. This is the reason why glucose is the most abundant hexose. All bulky groups are in equatorial position and all H-atoms are in axial position.

All hexoaldoses are stereoisomers of each other. For example galactose has a similar conformation as glucose except for the OH group in position 4. The 4-OH group in galactose is in axial position, whereas in glucose it is in equatorial position. Galactose is said to be a 4-epimer of glucose.

Ketoses Aldoses have one aldehyde group ( -CHO ) and several OH groups as functional groups, whereas ketoses have one carbonyl or keto group ( -CO- ) and several OH groups. The most common ketose is a hexose called fructose. It stereochemical arrangement of the OH groups is similar to glucose and if dissolved in water fructose will also form a cyclic compound: alpha (or beta) D-fructofuranose.

Polysaccharides As mentioned previously, the cyclization reaction in monosaccharides involves the reaction between an -OH group and an -CHO (or -CO-) group to the so called hemiacetal (this is the reaction which leads to the cyclization of hexoses, e.g. glucose to glucopyranose or fructose to fructofuranose). The hemiacetal group of one sugar can react with the OH group of a second sugar to form an acetal. This type of bond is called a glycosidic bond.

Since water is eliminated in the formation of the acetal, th`e reaction is classified as a condensation reaction as described above

Polysaccharides such as starch, cellulose and glycogen are formed in condensation reactions with glucose as the sole reactant, as shown below.

Starch (an energy storage polymer) and cellulose (a structural polymer) are straight chain carbohydrates, whereas glycogen (the storage form of glucose in animals) is a polysaccharide with alpha 1-4 linkages and occational alpha 1-6 cross linkages, i.e. it is a branched polysaccharide. As we will see later glucose is oxidized by the cell to CO2 and H2O in a reaction which releases much energy. This energy fuels all metabolic processes of the cell. Thus storage of glucose is very important. Rather than concentrating glucose, the cell converts it into a polymer which increases the storage capacity immensly. Glucose becomes easily available through hydrolysis of starch or glycogen. Amino Acids The general formula of alpha amino acids is shown below. Since the molecule contains a basic group (-NH2) and an acidic group (-COOH), the proton from the -COOH group is transferred to the amino group forming a positively charged (-NH3)+ and a negatively charged -COO- group. The amino acid becomes a zwitter ion since it contains both a positive and a negative charge. Since the alpha carbon has four differnt substituents all 20 common amino acids (except Gly) are optical active . They have L-configuration, which is interestingly opposite from the sugars (have D-configuration). Depending on the chemical nature of the side chain, there are polar, hydrophobic, aromatic, and ionic amino acids. (review the names of all 20 common amino acids, essential amino acids : Val, Ile Leu, Phe, Trp, Met, Thr, Lys).

Peptide bond Implication on the secondary structure of proteins.The planar stereochemistry of the peptide bond has important

Free rotation is only possible around the C-NH bond (phi) and the C-CO bond (psi) . Imaging that you would rotate phi by 180o, the two negatively charged oxygen of the two CO groups would come too close and repell each other. Such a conformation would be instable and would never form. Similar, if you rotate psi by 180o, the two positively charged hydrogens of the two NH groups would be too close, repelling each other. Thus only a few angles of psi and phi result in stable conformations. Hydrogen bond formation along the helix axis produces four distinct structures. H-bonds between (dotted line) between the CO group an the NH group of the second amino acid causes the peptide to assume a ribbon structure. The structure is not very stable since the H-bonds have not a 180o geometry. H-bond interaction with the NH group of the third amino acid produces an 310 helix, which is more stable because of a better overlap of the CO -- H-N hydrogen bond. An exact 180o geometry is reached if the H-bond is form between the the carbonyl oxygen and the NH group of the fourth amino acid. The result in the famous alpha helix, which was discovered by Linus Pauling. The alpha helix is the most stable helical structure formed by proteins (picture of alpha-helix). Hydrogen bond formation with the fifth amino acid produces a pi helix, which is much wider than the alpha helix and also less stable. The three dimensional structure of proteins is essentially determined by its amino acid sequence. The protein chain will fold into a certain shape which is determined by the

interaction of the amino acid side chains with each other. Such interactions includes the formation of salt bridges, -S-S- bridges, Hbonds, polar interaction as well as hydrophobic interactions. Proteins exhibit 4 levels of structure: 1o: amino acid sequence 2o: helix (310, alpha, pi,) beta sheet 3o: three dimesional folding 4o: association of proteins with more than one petide chain

Proteins have many different functions: Structural proteins which form long fibers: alpha keratin (horns, hooves, nails, hairs etc.), Collagen (skin, catilage), microtubules and microfilaments: cellular support, cell division, cellular transport Enzymes: Catalyst for chemical reactions in living organisms

Transporter proteins: the flow of most substances in and out of the cell is controlled by these proteins Mobile transport vehicles : these proteins act as carrier molecules, distributing substances throughout the body (hemoglogin: O2 and CO2) Electron carriers: these proteins play an important role in the extraction of energy from food sources Antibodies : recognize and attach themselves to foreign proteins, which then are enzymatically degraded (hydrolyzed) Hormones: some proteins function as hormones, regulating e.g. blood glucose levels, and function of secretory glands. Actin and Myosin: proteins in muscles, which control contraction

Lipids Lipids are a class of non polar and polar cellular components. Phospholipids are the major building blocks of the biomembrane, a barrier which controls the flow of substances in and out of the cell. A major component of phospholipids are fatty acids. The structures of three fatty acids are shown below.

The molecule consists of a long aliphatic side chain (CH2 groups) and a carboxylic group (COOH). Thus, a fatty acid molecule has an very non polar or hydrophobic moiety (long tail of CH2 groups) and very polar COOH group capable of dissociating. Saturated fatty acids have no double bonds in their hydrophobic tails, whereas unsaturated fatty acids have one or more carbon carbon double bonds. The double bonds in these fatty acids have the cis orientation. Phospholipids consist of glycerol (an alcohol with three OH groups) to which two hydrophobic fatty acids residues are bonded via an ester bond. The remaining OH group is connected to a hydrophilic phosphate group which is attached to a polar alcohol. The plasma membrane is made up a double layer of these phospholipids. The orientation is such that the hydrophobic tails phase each other, and the hydrophilic head groups are pointing to the outside. The degree of unsaturation in the fatty acid tails controls the fluidity of the membrane. In addition to phospholipids the biomembrane also contain glycolipids, in which the polar head group consists of a sugar or oligosaccaride.

The other type of fatty acid containing lipids are triglycerides (also kown as fats) which function as energy storage molecules. They are formed by esterification of glycerol with three fatty acids. Depending on the content of unsaturated fatty acids, triglycerides can be solids (fats) or liquids (oils).

A third class of lipids are steroids such as cholesterol, which is abundant in the biomembrane. The hydrophilic OH group of the molecule is facing the oudside of the membrane and the hydrophobic ring portion is embedded in the interior. Steroids function also as hormones, regulating cellular metabolism, growth and reproduction. Nucleic Acids For review, please refer to your text book. You should know the names of the two purine bases adenine (A) and guanine (B) and the three pyrimidine bases cytosine (C), thymine (T) and uracil (U) and their occurrence in either DNA or RNA. Know which bases can pair via H-bonds. Problems: (funct. groups, amino acids, proteins, carbohydrates, lipids) 1. 2. 3. What causes optical activity in organic molecules? What is the configuration of naturally occuring sugars and amino acids? Hexoses differ in their chemical structure by the spacial orientation of their OH groups. Among all possible structures only a few exist in nature.Why? Why is glucose is the most abundant hexose ? 4. What is the name of a non polar, polar, acidic and basic amino acid? 5. Which of the following amino acids are either found on the exterior (E), interior (I) or on either side (EI) of globular proteins? Val, Phe, Gly, Lys, Asp. 6. Explain how Cys is involved in protein folding. Where (exterior, interior) would you expect to find Cys. 7. Outline the different levels of structural organization of proteins 8. For each of the polymers listed below indicate which properties apply. Cellulose, DNA, Fibrous (structural) proteins, Globular proteins, Starch, Glycogen 1. Branched chain polymer, 2. alpha linkage, 3. Peptide bond, 4. Helical structure is possible, 5. beta linkage, 6. phosphodiester bonds, 7. Informational polymer, 8. Denaturing (loss of its native structure) by increasing the pH 9. What is the structural difference between glucose and fructose? 10. What are the subunits of a fat and how are the bonded ? 11. What are the differences between saturated and unsaturated fats? Which is a liquid at room temperature? 12. Which type of fatty acids would you predominantly expect in the membrane of a thermophilic organism which lives in a pool at 60 degr.C ? How about a fish in the arctic ocean? Answer to Problems 1. 2. 3. assymetric carbon atom, a carbon atom that has four different substituents e.g. carbon 2 in glyceraldehyde sugars : D ; amino acids : L the structure of glucose is the most stable, since the OH groups (bulky groups) are all in equatorial position. The molecule is free of steric pressure and is thermodynamically stable. All other hexoses exhibit steric interference of the OH groups and are either instable or may not even be formed. non polar: Ala (Gly, Val, Leu, Ile, Phe) polar; Ser (Thr, Tyr, Trp, Asn Gln, Met, Cys) acidic: Asp (Glu) basic : Lys ( Arg, His) protein. Gly is also an amino acid with a non polar residue. However the residue is only a H-atom, Thus the non polar properties are not very dominant and Gly can be on the queous (exterior) side or the interior side of proteins. Lys, Asp are amino acids with ionic ) -NH3 and -COOH) residues and can only be on the exterior side. Cys-SH + HS-Cys form disulfide bridges Cys-S-S-Cys and can crosslink protein chains. Since the crosslinking brings two chain close Cys will always be postioned in the interior of the protein structure cellulose: 5 ; DNA: 4,6,7,8; Fibrous proteins: 3,4; Globular proteins: 3,4,8; Starch: 2; Glycogen: 1, 2 glucose = aldose ( has an aldehyde group, CHO) ; fructose = ketose ( has a keto group, C=O) glycerol + fatty acid bonded via ester bond unsaturated fats have double bonds. e.g. oils have highly unsaturated fatty acid chains and are liquid at room temperature. Thermophilic organisms : cellular membrane contains highly saturated fatty acids. Arctic fish : highly unsaturated fatty acid residues

4.

5. Val, Phe are amino acids with non polar residues , which can not interact with water and are therefore in the interior of the

6.

7. prim: amino acid sequence; sec: alpha helix (and beta sheet); tert: folding; quat: assoc. of individual peptide chains.
8. 9. 10. 11. 12.