AMINO ACID TUTORIAL AMINO ACIDS STRUCTURES AND NOMENCLATURE

Transcription

1 Tutorial 1: Amino acids Four tutorials are provided as recordings in MediaSpace. You might find it useful to have the following pages in front of you so that you can take notes as you listen to the recordings. AMINO ACID TUTORIAL AMINO ACIDS STRUCTURES AND NOMENCLATURE The structure and properties of amino acids are discussed in the tutorial, Knowing the structures of biologically important compounds facilitates the understanding of relationships between different biochemical pathways [e.g. between amino acid/nitrogen metabolism and the tricarboxylic acid (TCA) cycle/carbon metabolism]. Therefore, you DO need to be able to recognize and identify the structures of the side chains of amino acids. Suggested reading: Ferrier: p. 1-5, Chapter 1, I. Overview through II. Structure Objectives: 1. Identify and recognize the structures of the 20 primary amino acid components of proteins, as well as secondary amino acids. 2. Classify the amino acids based on their hydrophilicity/hydrophobicity. 3. Identify the chemical groups of amino acids that are important in buffering proteins. Measurable Outcomes: What you should be able to do A. List the amino acids and identify which are hydrophilic, which are hydrophobic, which have side chains charged at ph 7.0, and which are important in buffering by proteins. (Obj. 2 and 3) B. Recognize amino acid residues in polypeptide chains. (Obj. 1) C. Recognize the difference between primary and secondary amino acids. (Obj. 1) 1

2 Tutorial 1: Amino acids I. AMINO ACIDS A. General structural features H 2 N H C R kinds of side chains, differing in size, charge properties, hydrogen bonding and chemical reactivity 20 different amino acids = called the primary amino acids because are the ones coded for by the genes 2. In general, proteins of all species (bacteria to humans) are constructed from the same set of 20 amino acids. 3. Range of functions by proteins results from the diversity and versatility of the combination of the 20 a.a. B. Stereochemistry O C OH chiral carbon atom O C OH C C H 2 N R H H R NH 2 L-α-amino acid D-α-amino acid FOUR DIFFERENT groups bonded to a single carbon confers optical activity; this type of carbon is called a chiral carbon atom (a.k.a. chiral center or asymmetric carbon). two mirror images: L-isomer and D-isomer proteins isolated in nature (after hydrolysis in HCl) only L-amino acids are found Therefore, only L-amino acids are constituents of proteins 2

3 Tutorial 1: Amino acids C. The R groups of amino acids Name Symbol Structural Formula Characteristics With Aliphatic Side Chains Glycine Gly (G) H 2 N CH H Alanine Ala (A) H 2 N CH CH 3 Valine Val (V) H 2 N CH CH CH 3 CH 3 Leucine Leu (L) H 2 N CH CH 2 CH CH 3 CH 3 Isoleucine Ile (I) H 2 N CH CH CH 2 CH 3 CH 3 With Side Chains Containing Hydroxyl (-OH) Groups Serine Ser (S) H 2 N CH CH 2 OH Threonine Thr (T) H 2 N CH CH OH CH 3 Tyrosine Tyr (Y) H 2 N CH CH 2 OH With Side Chains Containing Acidic Groups or Their Amides Aspartic acid Asp (D) O H 2 N CH CH 2 C OH Asparagine Asn (N) O H 2 N CH CH 2 C NH 2 Glutamic acid Glu (E) O H 2 N CH CH 2 CH 2 C OH Glutamine Gln (Q) O H 2 N CH CH 2 CH 2 C NH 2 3

4 Tutorial 1: Amino acids Name Symbol Structural Formula Characteristics With Side Chains Containing Basic Groups Arginine Arg (R) H NH H 2 N CH CH 2 CH 2 CH 2 N C NH 2 Lysine Lys (K) H 2 N CH CH 2 CH 2 CH 2 CH 2 NH 2 Histidine His (H) H 2 N CH CH 2 N NH With Side Chains Containing Aromatic Rings Histidine His (H) H 2 N CH CH 2 N NH Phenylalanine Phe (F) H 2 N CH CH 2 Tyrosine Tyr (Y) H 2 N CH CH 2 OH Tryptophan Trp (W) H 2 N CH CH 2 N H With Side Chains Containing Sulfur Atoms Cysteine Cys (C) H 2 N CH CH 2 SH Methionine Met (M) H 2 N CH CH 2 CH 2 S CH 3 With Side Chains Containing Imino Acids Proline Pro (P) + H 2 N CH H 2 C CH 2 CH 2 4

5 Tutorial 1: Amino acids D. Secondary amino acids found in proteins 1. Are NOT coded for by the genes 2. Are formed from post-translational modifications (after synthesis of the polypeptide) 3. Secondary amino acids a. Cystine formed by a disulfide bond between two cysteines Intrachain disulfide bond: between Cys residues within the SAME polypeptide chain Interchain disulfide bond: between Cys residues on DIFFERENT polypeptide chains b. Hydroxyproline and hydroxylysine 4-hydroxyproline5-hydroxylysineH2CCH2CHOHCH+H2NH2NCHCH2CH2CH2NH2CHOH(1) Hydroxyl groups (-OH) are added (2) Note: Hydroxylation of Pro and Lys occurs in collagen c. Phosphoserine, phosphothreonine, and phosphotyrosine H2NCH2OO--OPOCHH2NCHCHCH3OPO--OOH2NCHCH2OP-OO-O(1) The addition of phosphate groups to amino acids with hydroxyl groups (2) Note: Phosphorylation of hydroxyl-containing amino acids in certain proteins regulates the activity d. Other modifications (1) Acetylation (i.e. histones) (2) Glycosylation (addition of sugars to make glycoproteins) (3) γ-carboxylation (addition of extra group) i.e. in blood clotting +2HcysteinecysteinecystineH2NCHCH2SHH2NCHCH2HSH2NCHCH2SH2NCHCH2S5

6 H2H2H2CH2CH2HOCHCH2NH2BMB 516 Tutorial 1: Amino acid problem set NAMINO ACID TUTORIAL PROBLEM SET H For the above molecules, identify which one is a secondary amino acid. HA. 1 B. 2 C. 3 D. 4 E. 5 A. 1 B. 2 C. 3 D. 4 E. 5 A. 1 B. 2 C. 3 D. 4 E. 5 HCCH2N2CHOH2. For the molecules shown above, identify which one is threonine. 3. Of the molecules shown above, identify which one is not a chiral amino acid. NCHHHNCCHC2CH2 4 H6 H2COOOH3N5 HC

7 Tutorial 1: Amino acid problem set For the peptide shown above, the amino acid side chains are numbered 1 through For the peptide shown above, which amino acids have hydrophilic side chains? A. 1 only B. 2 only C. 5 only D. All five E. None of them 5. For the peptide shown, which of the amino acids have side chains that can become ionized (charged) depending on the ph? A. 1 and 2 B. 2 and 3 C. 3 and 5 D. 2, 3, and 5 E. All five 6. For the peptide shown, identify the five amino acids that make up the peptide above HHOOOOOHHHHN2CCNCCNCCNCCNCCOHCHCHCHHHH222OHOHSH3CHCHH22COCH2CHNH122CH42NH2257

8 Tutorial 1: Amino acid problem set ANSWERS 1. E: Amino acid number 5 is 5-hydroxylysine. 2. D ANSWERS 3. C: Amino acid number 3 is glycine. Glycine is the only amino acid that is NOT chiral. Since its side chain is simply a hydrogen atom, it does not have 4 different groups attached to the alpha carbon atom. 4. D: All five of the amino acids that make up the peptide can be hydrophilic. Tyrosine can be either hydrophilic OR hydrophobic depending on the environment. 5. D: While all 5 can be hydrophilic, only 2, 3, and 5 can become charged is serine 2 is tyrosine 3 is cysteine 4 is asparagine 5 is lysine 8

9 Tutorial 2: Nucleotides NUCLEOTIDE TUTORIAL NUCLEOTIDES STRUCTURES AND NOMENCLATURE As background to our discussion on vitamins and DNA and RNA pathways, you need to learn their structures. The nucleotide tutorial can be found at You DO need to be able to recognize and identify the structures of the nucleotides as indicated in the objectives below. Suggested reading: Ferrier: p , Chapter 22, I. Overview through II. Structure Objectives: 1. Identify and recognize the structures of the components of DNA. 2. Identify and recognize the structures of the components of RNA. Measurable Outcomes: What you should be able to do A. Be able to distinguish between purine and pyrimidine nitrogenous bases. (Obj. 1 and 2) B. Recognize and name the structures of the common bases (adenine, guanine, cytosine, uracil, and thymine) and their corresponding ribo- and deoxyribo-nucleosides and nucleotides. (Obj. 1 and 2) C. Identify specific positions of principal carbon and nitrogen atoms in the common bases and corresponding ribo- and deoxyribo- nucleosides and nucleotides, using the conventional numbering system. (Obj. 1 and 2) 9

10 Tutorial 2: Nucleotides I. Nucleotide Structure and Nomenclature A. Three components of nucleotides: purine 1. nitrogenous base pyrimidine ribose 2. five-carbon sugar deoxyribose 3. phosphate B. Purine structures NNCCNCCNHHHCHNNCCNCCNHHCHNH2NCCNCCNHCHH2NNHOPurine Adenine (A) Guanine (G) CCCCNHCONHONHNHOCCCCNHCONHONHNHCCCCNHCONHNNHHCCCCNCONONHH3CCH3NCH3Uric Acid Xanthine Hypoxanthine (H) Caffeine (1,3,7-Trimethylxanthine) C. Pyrimidine structures NNCCCCHHHHNCCCCHHNH2ONHCCCCHHONHONHCCCCHONHONHCH3Pyrimidine Cytosine (C) Uracil (U) Thymine (T) 10

11 Tutorial 2: Nucleotides I. Nucleotide Structure and Nomenclature (continued) D. Nucleoside: base + sugar Purine or pyrimidine linked to D-ribose or 2-deoxy-D-ribose via an N-glycosidic bond 1'2'3'4'5'HOOHHHOHOHHCH2HO1'2'3'4'5'HOOHHHOHHCH2HOHβ-D-ribose β-2 -deoxy-d-ribose 3'2'HOHHOHOHHCH2HONNCCNCCNHCHNH ' 4' 5' 2'3'HOHHOHHCH2HOHNCCCCHHNH2ON ' 4' 5' Adenosine Deoxycytidine Nucleoside atomic numbering: Base = 1, 2, 3, Sugar = 1, 2, 3, E. Nucleotide: base + sugar + phosphate (ester) Adenosine-5 monophosphate diphosphate triphosphate Adenosine triphosphate (ATP) HOHHOHOHHCH2NNCCNCCNHCHNH2OPOO-OPOO-OPO-OO-11

12 Tutorial 2: Nucleotides I. Nucleotide Structure and Nomenclature (continued) F. Summary of nomenclature: Base Ribonucleoside Ribonucleotide (5 -monophosphate) Adenine (A) Adenosine Adenosine 5 -monophosphate (AMP); adenylate Guanine (G) Guanosine Guanosine 5 -monophosphate (GMP); guanylate Hypoxanthine (H) Inosine Inosine 5 -monophosphate (IMP); inosinate Cytosine (C) Cytidine Cytidine 5 -monophosphate (CMP); cytidylate Uracil (U) Uridine Uridine 5 -monophosphate (UMP); uridylate Base Deoxyribonucleoside Deoxyribonucleotide (5 -monophosphate) Adenine (A) Deoxyadenosine Deoxyadenosine 5 -monophosphate (damp); deoxyadenylate Guanine (G) Deoxyguanosine Deoxyguanosine 5 -monophosphate (dgmp); deoxyguanylate Cytosine (C) Deoxycytidine Deoxycytidine 5 -monophosphate (dcmp); deoxycytidylate Thymine (T) Deoxythymidine Deoxythymidine 5 -monophosphate (dtmp); deoxythymidylate G. Examples of nucleotide functions: 1. nucleic acid biosynthesis 2. energy transfer 3. coenzyme components 4. carbohydrate, lipid metabolism 5. hormonal activity 6. allosteric regulation of enzymes and regulatory proteins 12

13 Tutorial 2: Nucleotides problem set NUCLEOTIDE TUTORIAL PROBLEM SET 1. Which of the structures below is used in energy transfer reactions? Identify which of the structure(s) below are components only of DNA (not RNA) HOHHOHOHHCH2NNCCNCCNHCHNH2OPOO-OPOO-OPO-OO-HOHHOHHCH2HNNCCNCCNHCHNH2OPOO-OPOO-OPO-OO-HOHHOHHCH2HNCCNCCNCHH2NNHOOPOO-OPOO-OPO-OO-HOHHOHHCH2HNCCCCHHNH2ONOPOO-OPOO-OPO-OO-CCCCHHONHONHHOHHOHOHHCH2NCCNCCNCHH2NNHOOPO-OO-HOHHOHHCH2HNCCCCHHNH2ONOPO-OO-HOHHOHHCH2HCCCCHONONHCH3OPO-OO-HOOHHHOHHCH2HOH13

14 Tutorial 2: Nucleotides problem set 3. a. Match the following names or abbreviations to the structures below (not all of the choices will be used) A. datp I. inosine 5 -diphosphate B. hypoxanthine J. cytosine C. guanine K. inosine D. deoxyguanosine L. thymidine 5 -diphosphate E. CDP M. uric acid F. guanosine N. deoxyadenosine G. uracil O. cytidine H. uridine 5 -diphosphate P. dttp b. Classify each of the 6 structures in part a as a purine base, pyrimidine base, ribonucleoside, deoxyribonucleoside, ribonucleotide, or deoxyribonucleotide. HOHHOHHCH2HCCCCHONONHCH3OPOO-OPOO-OPO-OO-NCCCCHHNH2ONHCCCCNHCONHONHNHOHOHHOHOHHCH2HOCCCCNCONHNNHHHOHHOHHCH2HOHNCCNCCNCHH2NNHOHOHHOHOHHCH2CCCCHHONONHOPOO-OPO-OO-14

15 Tutorial 2: Nucleotides problem set ANSWERS NUCLEOTIDE TUTORIAL ANSWERS TO PROBLEM SET 1. Molecule 4 is ATP the primary chemical form of energy used in biochemical pathways. (Note: The other 3 molecules are all deoxyribonucleotides. The deoxyribonucleotide forms are not used as chemical forms of energy in biochemical reactions.) 2. Molecule 1 is dtmp; Molecule 3 is dcmp; Molecule 5 is deoxyribose. All three of these are components only of DNA molecules. Recall any of the bases (except uracil Molecule 4) attached to deoxyribose are only components of DNA. Molecule 2 is GMP a ribonucleotide. Bases attached to ribose (except thymine) are used in making RNA. 3. Molecule 1 J. cytosine; a pyrimidine Molecule 2 P. dttp; a deoxyribonucleotide [Note: because the deoxy is understood for thymidine, you may also see it abbreviated TTP; or TMP and TDP for the monoand di-phosphate forms] Molecule 3 M. uric acid; a purine Molecule 4 K. inosine; a ribonucleoside Molecule 5 H. uridine 5 -diphosphate; a ribonucleotide Molecule 6 D. deoxyguanosine; a deoxyribonucleoside 15

16 Tutorial 3: Carbohydrates (Part 1) CARBOHYDRATE TUTORIAL: PART 1 IMPORTANT: Read through the section I. Terminology and Rules for Carbohydrate Structure Recognition (the first two pages). If you understand and can apply these terms and rules to carbohydrate structures, then you do not need to listen to the Carbohydrate Tutorial: Part 1. Therefore, this part is designated as OPTIONAL. If you have never had a biochemistry course and/or you do not recall these terms and how to apply them, it would be in your best interest to listen to Part 1 of the tutorial on carbohydrates. You are responsible for understanding these terms and rules whether or not you listen to the optional tutorial. The CARBOHYDRATE TUTORIAL: Part 1 can be found at: The optional carbohydrate tutorial covers these terms and rules by providing examples and explaining the relationship between D and L carbohydrates as well as the relationship between the linear and cyclical structures of carbohydrates. Be sure to read through the terms and rules before listening to the optional tutorial. The tutorial will cover the terms and rules using examples, but these two pages will NOT be read directly on the tutorial recording. OBJECTIVES: 1. Recognize the linear and cyclic structures of glucose, galactose and fructose. 2. Know and be able to apply the definitions of isomer, enantiomer, diastereomer, epimer, anomer, aldose, ketose, pyranose, furanose, D- and L-sugars, deoxysugar, amino sugar, -onic sugar, -uronic sugar, hemiacetal, acetal, glycoside, reducing end, and non-reducing end. 16

17 Tutorial 3: Carbohydrates (Part 1) I. Terminology and Rules for Carbohydrate Structure Recognition A. Definitions: 1. Stereoisomers (a.k.a. isomers) different compounds that have the same structure, differing only in the arrangement of the atoms in space. 2. Chiral any object that cannot be superimposed on its mirror image (i.e. your right and left hands are non-superimposable mirror images). A plain cup would be achiral superimposable on its mirror image. 3. Enantiomers a pair of stereoisomers that are non-superimposable mirror images; i.e. a chiral molecule and its mirror image molecule (note: these two molecules are DIFFERENT compounds). Examples: the D and L series of sugars and amino acids. 4. Diastereomers non-enantiomeric stereoisomers (are NOT mirror images, though they have the same number of each atom i.e. the same number of carbons, oxygens, and hydrogens). Example: galactose and mannose 5. Epimers diasteromers that differ at only one of their chiral carbon atoms (i.e. glucose and galactose). 6. Anomeric carbon the carbonyl carbon in any monosaccharide. This is the carbon that becomes chiral in the cyclization reaction resulting in an α- or β- sugar. 7. Anomers diastereomers of monosaccharides that differ only in the configuration at carbon 1 (for the aldoses). For the ketoses, they would differ at carbon 2 because carbon 2 is the carbonyl carbon in the straight-chain form. 8. Furanose ring a monosaccharide in the form of a 5-membered oxygen heterocycle (4 carbons and an oxygen in the ring). 9. Pyranose ring a monosaccharide in the form of a 6-membered oxygen heterocycle (5 carbons and an oxygen in the ring). 10. Carbohydrates polyhydroxyl aldehydes and ketones and their derivatives 11. Hemiacetal the product of a reaction between an aldehyde and an alcohol. 12. Reducing group the aldehyde group or hemiacetal group of an aldose sugar. 13. Digestion catalyzed hydrolysis of complex dietary compounds to simpler ones which can be absorbed. 17

18 Tutorial 3: Carbohydrates (Part 1) 14. Glycosidic bonds bonds linking sugars to each other in disaccharides and polysaccharides. They form by reaction of the OH group of a hemiacetal and another alcohol group with the loss of H2O. The products are termed glycosides in general, or more specifically glucosides, galactosides, etc., for a particular sugar, donating the hemiacetal group. 15. Dextrin product of hydrolysis of glycosidic bond of a polysaccharide leaving a relatively large oligo or smaller polysaccharide the dextrin. B. Other Rules in regards to carbohydrates: 1. The highest numbered asymmetric (chiral) carbon determines the configuration of D or L. a. Example: In the Fischer projection (the straight chain form) for the aldoses (aldehyde sugars), all of the aldehyde groups are carbon #1 and the last carbon in the chain is CH2OH (also a non-chiral carbon). Thus the carbon just before the CH2OH is the highest numbered asymmetric carbon. b. If the highest numbered asymmetric carbon has an OH group pointing to the right in this Fischer projection, it is a D-sugar. c. If the highest numbered asymmetric carbon has an OH group pointing to the left, it is an L-sugar. 2. In the Haworth (ring) structures by convention, the oxygen atom in the pyranose ring is in the upper right corner and carbon #1 is the first carbon below and to the right of this oxygen. 3. By convention in the Haworth ring structures, the D-sugars all have the terminal CH2OH group pointing up from the plane of the ring. The L-sugars have the terminal CH2OH group pointing down from the plane of the ring. 4. Also, any group that points to the RIGHT in the Fischer (straight-chain) projection, points DOWN in the Haworth (ring) structure; any group that points to the LEFT in the Fischer projection, points UP in the Haworth structure. 5. For the alpha (α) and beta (β) anomers of sugars: a. if the OH group on carbon 1(of the aldoses) points down from the plane of the ring for D-sugars (meaning it is trans- to the terminal CH2OH), it is the alpha-anomer. Note: this applies to carbon 2 of the ketoses. b. if the OH group on carbon 1 (of the aldoses) points up from the plane of the ring for D-sugars (meaning it is cis- to the terminal CH2OH), it is the beta-anomer. Note: this applies to carbon 2 of the ketoses. 6. Aldoses are reducing sugars because aldehydes can be further oxidized to a carboxylic acid (thus they REDUCE something else). Ketoses (generally) are NOT reducing sugars because their anomeric carbon is not free ketones CANNOT be further oxidized, thus they CANNOT reduce something else. 18

19 Tutorial 3: Carbohydrates (Part 1) OPTIONAL CARBOHYDRATE TUTORIAL Examples of Terminology and Rules for Carbohydrate Structure Recognition I. The aldose (aldehyde) sugars from 3 to 6 carbons in length A. The chiral carbons outlined in blue all have the OH group pointing to the right. This is the highest asymmetric carbon that indicates all of these sugars are D-sugars. B. The chiral carbons outlined in brown are the new carbons introduced in going from a 3 carbon to a 4 carbon sugar, or 4 carbon to 5 carbon, etc. The OH group on these carbons can point either right or left, yielding 2 different sugars (i.e. erythrose and threose). C. Note: the hierarchy shown below does NOT indicate how these sugars are synthesized only how all of these sugars are related to one another. CCOHHOHCH2OHCCH2OHCCOHOHOHHHCH2OHCCOHOHHHCCHOHHOCH2OHCCOHOHHHCCHOHOHCH2OHCCOHHHOHCCOHOHHCH2OHCCOHHHOHCCOHHOHCH2OHCCOHOHHHCOHHCOCHOHHCH2OHCCOHOHHHCOHHCOCHHOHCH2OHCCOHOHHHCHHOCOCHOHHCH2OHCCOHOHHHCHHOCOCHHHOCH2OHCCHOHHOHCOHHCOCHOHHCH2OHCCHOHHOHCOHHCOCHHOHCCH2OHCCOHOHHHOHCH2OHCCHOHHOHCHHOCOCOHHHCH2OHCCHOHHOHCHHOCOCHHHOD-glyceraldehydeD-erythroseD-threoseD-ribose(rib)D-arabinose(ara)D-xylose(xyl)D-lyxose(lyx)D-aloseD-altroseD-glucose(glc)D-mannose(man)D-guloseD-idoseD-galactose(gal)D-talose CarbonnumberALDOTRIOSEALDOTETROSESALDOPENTOSESALDOHEXOSES19

20 Tutorial 3: Carbohydrates (Part 1) OPTIONAL CARBOHYDRATE TUTORIAL (continued) II. The relationship between D and L sugars III. The linear and cyclical structures of monosaccharides A. D-glucose: an aldose (an aldehyde sugar) CH2OHCCCCCOHHOHHOHHHOHOHOCCCCCHCH2OHHOHHOHHOHHOHOCCCCCHCH2OHHOHHOHHOHOHHOR (specialformof ) -D-glucopyranose -D-glucopyranose (formedbyreactionofanaldehyde+alcohol)cch2ohhohchohcohhccohhhoch2ohccohohhhchhocochohhcch2ohhohchohchhoccohohhl-idose L-glucose D-glucose 20

21 Tutorial 3: Carbohydrates (Part 1) OPTIONAL CARBOHYDRATE TUTORIAL (continued) 2. D-fructose: a ketose (a ketone sugar) CH2OHCCCCCH2OHHOHHHOHOHOOCH2OHOHOHHOHHCH2OHHOOHHOHHCH2OHHOHCH2OHOR -D-fructofuranose -D-fructofuranose (formedbyreactionofaketone+alcohol)21

22 Tutorial 4: Carbohydrates (Part 2) CARBOHYDRATE TUTORIAL: PART 2 IMPORTANT: Read through the Terminology and Rules for Carbohydrate Structure Recognition section (the first two pages). If you understand and can apply these terms and rules to carbohydrate structures, you do not need to listen to the optional Part 1 of the carbohydrate tutorial. These concepts are not discussed in detail in this Part 2 of the carbohydrate tutorial. If you have never had a biochemistry course and/or you do not recall these terms and how to apply them, it would be in your best interest to listen to the optional Part 1 of the tutorial on carbohydrates You are responsible for understanding these terms and rules whether or not you listen to the optional tutorial as well as the further details (as defined by the objectives below) in this Part 2 of the carbohydrate tutorial. CARBOHYDRATE TUTORIAL: PART 2 can be found at: This will be referred to as REQUIRED, to distinguish it from the optional Part 1. Suggested reading: Ferrier: p , Chapter 7, I. Overview through II. Classification and Structure Objectives: 1. Know common terminology as applied to the chemical structures of carbohydrates and their derivatives. 2. Recognize linear and cyclical structures of common biological sugars and their derivatives, particularly glucose, galactose, and fructose. 3. Identify the carbohydrates components of common disaccharides (i.e. sucrose, lactose, and maltose) and complex carbohydrates and know their biological significance. Measurable Outcomes: What you should be able to do A. Recognize the linear and cyclic structures of glucose, galactose, and fructose. (Obj. 2) B. Know and be able to apply the definitions of aldose, ketose, pyranose, furanose, D- and L-sugars, epimer, anomer, deoxysugar, amino sugar, -onic sugar, -uronic sugar, hemiacetal, acetal, glycoside, reducing end, and non-reducing end. (Obj. 1, 2 and 3) C. Recognize simple sugars, sugar acids, amino sugars, sugar alcohols, complex sugars and proteoglycans. Know their metabolic, functional and structural significance. (Obj. 1, 2, and 3) D. Recognize and know how to identify and designate the carbons involved in alpha (α) versus beta (β) linkages of sugars. (Obj. 1 and 3) NOTE: Do the practice problem set at the end of this tutorial section. 22

23 Tutorial 4: Carbohydrates (Part 2) Terminology and Rules for Carbohydrate Structure Recognition A. Definitions: 1. Stereoisomers (a.k.a. isomers) different compounds that have the same structure, differing only in the arrangement of the atoms in space. 2. Chiral any object that cannot be superimposed on its mirror image (i.e. your right and left hands are non-superimposable mirror images). A plain cup would be achiral superimposable on its mirror image. 3. Enantiomers a pair of stereoisomers that are non-superimposable mirror images; i.e. a chiral molecule and its mirror image molecule (note: these two molecules are DIFFERENT compounds). Examples: the D and L series of sugars and amino acids. 4. Diastereomers non-enantiomeric stereoisomers (are NOT mirror images, though they have the same number of each atom i.e. the same number of carbons, oxygens, and hydrogens). Example: galactose and mannose 5. Epimers diasteromers that differ at only one of their chiral carbon atoms (i.e. glucose and galactose). 6. Anomeric carbon the carbonyl carbon in any monosaccharide. This is the carbon that becomes chiral in the cyclization reaction resulting in an α- or β- sugar. 7. Anomers diastereomers of monosaccharides that differ only in the configuration at carbon 1 (for the aldoses). For the ketoses, they would differ at carbon 2 because carbon 2 is the carbonyl carbon in the straight-chain form. 8. Furanose ring a monosaccharide in the form of a 5-membered oxygen heterocycle (4 carbons and an oxygen in the ring). 9. Pyranose ring a monosaccharide in the form of a 6-membered oxygen heterocycle (5 carbons and an oxygen in the ring). 10. Carbohydrates polyhydroxyl aldehydes and ketones and their derivatives 11. Hemiacetal the product of a reaction between an aldehyde and an alcohol. 12. Reducing group the aldehyde group or hemiacetal group of an aldose sugar. 13. Digestion catalyzed hydrolysis of complex dietary compounds to simpler ones which can be absorbed. 23

24 Tutorial 4: Carbohydrates (Part 2) 14. Glycosidic bonds bonds linking sugars to each other in disaccharides and polysaccharides. They form by reaction of the OH group of a hemiacetal and another alcohol group with the loss of H2O. The products are termed glycosides in general, or more specifically glucosides, galactosides, etc., for a particular sugar, donating the hemiacetal group. 15. Dextrin product of hydrolysis of glycosidic bond of a polysaccharide leaving a relatively large oligo or smaller polysaccharide the dextrin. B. Other Rules in regards to carbohydrates: 1. The highest numbered asymmetric (chiral) carbon determines the configuration of D or L. a. Example: In the Fischer projection (the straight chain form) for the aldoses (aldehyde sugars), all of the aldehyde groups are carbon #1 and the last carbon in the chain is CH2OH (also a non-chiral carbon). Thus the carbon just before the CH2OH is the highest numbered asymmetric carbon. b. If the highest numbered asymmetric carbon has an OH group pointing to the right in this Fischer projection, it is a D-sugar. c. If the highest numbered asymmetric carbon has an OH group pointing to the left, it is an L-sugar. 2. In the Haworth (ring) structures by convention, the oxygen atom in the pyranose ring is in the upper right corner and carbon #1 is the first carbon below and to the right of this oxygen. 3. By convention in the Haworth ring structures, the D-sugars all have the terminal CH2OH group pointing up from the plane of the ring. The L-sugars have the terminal CH2OH group pointing down from the plane of the ring. 4. Also, any group that points to the RIGHT in the Fischer (straight-chain) projection, points DOWN in the Haworth (ring) structure; any group that points to the LEFT in the Fischer projection, points UP in the Haworth structure. 5. For the alpha (α) and beta (β) anomers of sugars: a. if the OH group on carbon 1(of the aldoses) points down from the plane of the ring for D-sugars (meaning it is trans- to the terminal CH2OH), it is the alpha-anomer. Note: this applies to carbon 2 of the ketoses. b. if the OH group on carbon 1 (of the aldoses) points up from the plane of the ring for D-sugars (meaning it is cis- to the terminal CH2OH), it is the beta-anomer. Note: this applies to carbon 2 of the ketoses. 6. Aldoses are reducing sugars because aldehydes can be further oxidized to a carboxylic acid (thus they REDUCE something else). Ketoses (generally) are NOT reducing sugars because their anomeric carbon is not free ketones CANNOT be further oxidized, thus they CANNOT reduce something else. 24

25 Tutorial 4: Carbohydrates (Part 2) I. Carbohydrates A. What are carbohydrates? 1. Polyhydroxyl aldehydes, ketones, AND their derivatives 2. Originally they were thought to contain only a simple sugar formula (CHO), however, this is too simple, since sugars can be modified and some contain,, and groups. B. General classifications 1. Monosaccharide simple, single unit sugar (i.e. glucose) 2. Disaccharide contains 2 monosaccharides linked by a glycosidic bond a. Maltose grains b. Sucrose table sugar c. Lactose milk sugar 3. Polysaccharide a. Long polymer of monosaccharides b. Examples: starch and glycogen 4. Complex sugars a. A polysaccharide attached to a non-sugar molecule b. Examples: glycoproteins and glycolipids 5. Sugar derivatives a. Sugars with substitutions or functional groups at one or more of their hydroxyl groups b. Example: β-d-glucose-1-phosphate II. Carbohydrate Structures and Functions A. Monosaccharides 1. D-glucose a. A major source of through glycolysis b. Aldose: an aldehyde sugar CH2OHCCCCCOHHOHHOHHHOHOHOCCCCCHCH2OHHOHHOHHOHHOHOCCCCCHCH2OHHOHHOHHOHOHHOR (specialformof ) -D-glucopyranose -D-glucopyranose (formedbyreactionofanaldehyde+alcohol)25

26 Tutorial 4: Carbohydrates (Part 2) II. Carbohydrate Structures and Functions A. Monosaccharides (continued) 2. D-fructose a. An intermediate in glycolysis b. An isomer of D-glucose converted by an c. Ketose: a ketone sugar 3. D-galactose a. Part of lactose b. A building block of many polysaccharides c. An epimer of glucose (at C-4) converted by an CH2OHCCCCCH2OHHOHHHOHOHOOCH2OHOHOHHOHHCH2OHHOOHHOHHCH2OHHOHCH2OHOR -D-fructofuranose -D-fructofuranose (formedbyreactionofaketone+alcohol)ch2ohcccccohhohhohhohhhoch2ohcccccohhohhohhhohohd-galactosed-glucose213456ch2ohccccch2ohhohhhohohoch2ohcccccohhohhhohohhohd-fructosed-mannose26

27 Tutorial 4: Carbohydrates (Part 2) II. Carbohydrate Structures and Functions B. Disaccharides (two monosaccharides linked by a glycosidic bond) 1. Maltose a. A starch derivative b. + (α-1,4-d-glucoside) 2. Lactose a. Primary sugar found in milk b. + (β-1,4-glycoside) 3. Sucrose a. Table sugar b. An inverted sugar because fructose is inverted c. + (α-β -1,2 -glycoside) OCH2OHOHOHOHOCH2OHOHOHOHOOCH2OHOHOHOHOCH2OHOHOHOHOOCH2OHOHOHOHOH -D-glucoseOCH2OHOHOHCH2OHHOH -D-fructoseOCH2OHOHOHOHOCH2OHOHOHCH2OHOOCH2OHOHOHOHOCH2OHOHOHHCH2OHO '2'3'4'5'6'27

28 CHO2HH2OHO2HCHO2HOOOOOHOOHOHOOHOHOHOHOHOHBMB 516 Tutorial 4: Carbohydrates (Part 2) II. Carbohydrate Structures and Functions C. Polysaccharides (polymers of monosaccharides) 1. Structural polysaccharides a. Cellulose (1) Major structural building block of plant cell walls (2) An insoluble fiber (3) A glucose polymer with β-1,4-glycosidic bonds COn CHb. Glycosaminoglycans (1) Major structural polysaccharide in vertebrates (2) Family of linear polymers composed of repeating disaccharide units (3) One of the two monosaccharides is always either N-acetylglucosamine or N-acetylgalactosamine (4) Examples: dermatan sulfates ( ), keratan sulfates, and hyaluronic acid ( ) 28

29 Tutorial 4: Carbohydrates (Part 2) II. Carbohydrate Structures and Functions C. Polysaccharides (continued) 2. Storage polysaccharides a. Energy storage especially important to muscle tissue b. Glucans are polymers of glucose c. (a glucan) (1) Primary storage polysaccharide for animals and microbial cells (2) Branched polymer with α-1,4 and α-1,6-glucose linkages CH2OHOHOHOHOCH2OHOHOHOOOHOHOCH2OHOHOHOOOCH2OHOHOHOOOHCH2CH2OHOHOHOHOOCH2OHOHOHOOglycogenD. Complex sugars 1. Sugar components attached to non-sugar molecules 2. Examples: a. : blood group antigens b. : cell surface antigens c. : components of the extracellular matrix; has more sugar, less protein (huge molecules) 29

30 Tutorial 4: Carbohydrates (Part 2) II. Carbohydrate Structures and Functions E. Sugar derivatives 1. Sugar phosphates a. Sugars that contain one or more phosphate groups b. Used in glycolysis and polysaccharide formation 2. Deoxysugars a. Formed by the reduction of on the sugar b. Essential building blocks of DNA 3. Amino sugars a. Are amino derivatives of simple sugars b. Primarily building blocks for polysaccharides and polymers for cartilage and mucous CH2OPO32-OHOHOHOOH -D-glucose6-phosphateHOOHHHOHOHHCH2HOHOOHHHOHHCH2HOH -D-ribose -D-deoxyriboseCH2OHNH3OHOHOOH -D-glucosamine[2-amino-2-deoxy- -D-glucopyranose]30

31 Tutorial 4: Carbohydrates (Part 2) II. Carbohydrate Structures and Functions E. Sugar derivatives (continued) 4. Sugar acids a. The oxidation of either (or both) end carbons of a sugar to a carboxylic acid b. Often form stable cyclical structures with loss of H2O to form lactones c. Examples: (1) Gluconic acid: C-1 of glucose is oxidized to (2) Glucuronic acid: C-6 of glucose is oxidized to (3) Glucaric acid: Both C-1 and C-6 of glucose is oxidized to (4) Vitamin C has the lactone functionality of the carboxylic acid group 5. Sugar alcohols a. The C-1 positions of sugars are reduced to alcohols b. Example: glucose converted to sorbitol (sorbitol is an intermediate in the conversion of glucose to fructose) CH2OHCCCCCOHHOHHOHHHOHOHCH2OHCCCCHOHHOHHHOHOHCCCCCOHHOHHOHHHOHOHCCCCHOHHOHHHOHOHD-glucoseD-gluconicacidD-glucuronicacidglucaricacidOOCHOHCH2OHHOOHOOCHOHCH2OHOOascorbicaciddehydroascorbicacidVitaminCCH2OHCCCCCOHHOHHOHHHOHOHCH2OHCCCCCH2OHHOHHOHHHOHOHD-glucosesorbitol31

32 Tutorial 4: Carbohydrates (Part 2) CARBOHYDRATE TUTORIAL PROBLEM SET 1. Draw the alpha (α) and beta (β) anomers of galactose and mannose. 2. Which of the structures shown below are enantiomers? Which of the following structures are epimers? Which are anomers? CH2OHCCOHOHHHCHHOCOCHOHHCCH2OHHOHCHOHCOHHCCOHHHOCCH2OHHOHCHOHCHOHCCOHOHHCCH2OHHOHCHOHCHHOCCOHOHHCH2OHCCOHOHHHCOHHCOCHOHHHOOHHHOHOHHCH2HOOCCCCCHCH2OHHOHHOHHOHOHHOCCCCCHCH2OHHOHHOHHOHHOHOCCCCCHCH2OHHOHHOHOHHOHHOOHHOHHCH2OHHOHCH2OH32

33 Tutorial 4: Carbohydrates (Part 2) 4. Identify the two sugars, the linkage, and the reducing end of the following disaccharide. CARBOHYDRATE TUTORIAL ANSWERS TO PROBLEM SET 1. α-d-galactose β-d-galactose α-d-mannose β-d-mannose OCCCCCCH2OHOHOHOHOCCCCCCH2OHOHOHOHOOCCCCCHCH2OHHOHHOHHOHOHHOCCCCCHCH2OHHOHHOHOHHOHHOCCCCCHCH2OHHOHHOHOHHOHHOCCCCCHCH2OHHOHHOHHOHOHH33

34 Tutorial 4: Carbohydrates (Part 2) 2. Molecules 1 (D-glucose) and 4 (L-glucose) are enantiomers non-superimposable mirror images. Note that the aldehyde group and the CH2OH groups are not chiral and can be easily rotated to complete the mirror image. Molecule 2 is an L-sugar, but it is not an enantiomer of molecule 1 because it is not a mirror image it only differs at the configuration of carbon 5. Molecules 3 and 5 are D- and L-sugars, respectively. Again, they only differ at the configuration of carbon 5 and thus are not enantiomers (not mirror images). 3. Molecule 1 (α-d-glucose) and Molecule 2 (α-d-galactose) are epimers only differing at one carbon in configuration. Molecule 2 (α-d-galactose) and Molecule 5 (β-d-galactose) are anomers a special class of epimers differing only at carbon 1 in configuration. [So technically, these two are epimers, too just a special case.] Note: Molecule 3 is β-d-fructose and Molecule 4 is β-d-ribose these are not isomers at all. Fructose has 6 carbons and ribose only has 5 carbons. 4. The two sugars linked in this disaccharide are both galactose (actually they are both β-dgalactose). The linkage is a 1,4-β-glycosidic linkage. (Note the junction from carbon 1 of the first galactose points up meaning the OH group that was originally on that anomeric carbon was in the beta configuration.) This disaccharide does have a reducing end. It is the free anomeric carbon (carbon #1) of the second galactose because its OH group is still free not tied up in a glycosidic bond. 34