University of Khartoum Faculty of Medicine Department of Biochemistry MSc of Biochemistry By course

Assignment on :

Isomerism in Biomolecules

Prepared by: Naji Mohammed Elfatih Ibrahim

Supervisor : Prof. Abdulrahim Osman

Introduction
The chemistry of living organism is organized around carbon atom, which account for more than half of the dry weight of cells. Carbon atom can form single bond with hydrogen atom; can form both single and double bonds with oxygen and nitrogen atoms, but the most interesting it can form very stable carbon-carbon single bond. Each carbon can form single bond with up to four other carbon atoms. Two carbons can share two or three electron pairs thus forming double or triple bonds. Carbon carbon bond allow atoms to arrange in more versatile complex structure: linear, cyclic, branched or even planner. (1) Carbon skeleton is the backbone of organic molecules, to which sometimes a group of other atoms is added, this is called a functional group. The functional groups, the covalent bonds and the arrangement of the molecules atoms in three -dimensional space are central to its function (2)

Isomers and isomerism

Carbon containing compounds commonly exist as isomers, they show isomerism Isomerism can be defined as phenomenon by virtue of which two or more compounds having same molecular formula can be assigned different molecular structures and isomers are molecules with the same molecular formula, but different arrangements of atoms (3) Isomers can be broadly classified into two categories, structural isomers or constitutional isomers and stereoisomers. Further both types can be classified on the basis of their structural difference and orientation in three dimensional space.(3)

Structural isomers
Structural isomers have different molecular structures due to different arrangement of atoms in their molecules. They differ in the order in which the atoms are connected with each other so they contain different functional groups and or bonding patterns like branching

There are five types of structural isomers: chain isomers, positional isomers, functional isomers, tautomers and metamers (3) Chain isomers are differing in their skeletons of carbon atoms; therefore arise due to the possibility of branching of carbon chain. The most interesting chain isomers are the amino acids leucine and isoleucine

Positional isomers have different positions of functional groups or multiple bonds. I think alanine and alanine are good example for a positional isomerism with different position of functional group

Also the two 18 3 polyunsaturated fatty acids linolenic acid and linolenic acid show positional isomerism with different position of double bond

Isomers with different functional group belongs to different families are functional isomers of each other, and of course glucose is functional isomer of fructose since glucose is an aldose but fructose is a ketose. Aldose ketose isomerism of monosaccharide is good example of functional isomerism

Tautomerism is a special type of functional isomerism, in which isomers exist simultaneously in dynamic equilibrium with each other. It arises due to 1, 3-migration of hydrogen atom from one polyvalent atom to other within the same molecule. The best example of tautomerism in nucleotides where The oxo and amino groups of purines and pyrimidines exhibit keto-enol and amine-imine tautomerism, but physiologic conditions strongly favor the amino and oxo forms (4)

Metamerism differ in structure due to difference in the distribution of carbon atoms about the functional group. Metamerism is common in ether and secondary amines

Stereoisomers
Stereoisomers are molecules with the same constitution and sequence of carbon bonds but differ in their relative positions of atoms or groups in space their stereochemistry. Interactions between biomolecules are invariably stereospecific requiring specific stereochemistry in the interacting molecules Stereoisomers can be either configurational isomers or conformational isomers

Configurational isomers
Configurational isomers have different three dimensional relationship of bonded group about one or more atoms. They are either geometrical ( cis-trans) isomers or optical isomers Geometrical isomers differ in the spatial position around a carbon-carbon double bond due to restricted rotation. If same groups are placed on same side of the double bonded carbon atom, they known as cis-isomer. If same groups are placed on opposite side of double bonded carbon atom, they are called as trans-isomers. Trans and cis-isomers show different physical and chemical properties like melting point, boiling point and other chemical reactions(3) Maleate is cis isomer and fumarate is trans isomer; each is a well-dened compound that can be separated from the other, and each has its own unique chemical properties. A binding site (on an enzyme,for example) that is complementary to one of these molecules would not be complementary to theother,which explains why the two compounds have distinct biological roles despite their similar chemistry . Naturally occurring unsaturated long-chain fatty acids are nearly all of the cis configuration, the molecules being bent 120 degrees at the double bond. Thus has an L shape, where as molecules with trans remains straight. Increase in the number of cis double bonds in a fatty acid leads to a variety of possible spatial configurations of the moleculeeg, arachidonic acid, with four cis double bonds, haskinks or a U shape. This has profound significance on

molecular packing in membranes and on the positions occupied by fatty acids in more complex molecules such as phospholipids. Trans double bonds alter these spatial relationships.(4)

Trans fatty acids are present in certain foods, arising as a by-product of the saturation of fatty acids during hydrogenation, or hardening, of natural oils in the manufacture of margarine. An additional small contribution comes from the ingestion of ruminant fat that contains trans fatty acids arising from the action of microorganisms in the rumen (4)

Also cis trans isomerization play vital role in the physiology of night vision .In the retina 11cis- retinal a prothetic group of rodopsin the conjugated visual protein, is converted by light to all trans retinal and nerve impulse is generated (2)

Optical isomerism In optical isomerism four different substituents bonded to a tetrahedral carbon atom maybe arranged in two different ways in spacethat is, have two congurations yielding two stereoisomer. If they are mirror image of each other and not superposible they are also called as enantiomers. ( 3)

Those optical isomers which are not mirror images, known as diastereomers or diastereoisomers (3)

There are some essential conditions for optical isomerism. The molecule must be asymmetrical in nature; with no plane of symmetry. and has at least one chiral carbon atom.(3) A carbon atom with four different substituents is said to be asymmetric, and asymmetric carbons are called chiral centers (Greek chiros, hand; some stereoisomersare related structurally as the right hand is to the left) .A molecule with only one chiral carbon can have two stereoisomers; when two or more (n) chiral carbons are present, there can be 2 stereoisomers. (2)

Monosaccharides have chiral centers, for an aldose there are chiral centers equal to ( C - 2 ) where are C is the number of carbon atoms in the molecule , for ketoses it is less, equal to ( C-3 ) Glucose, an aldoshexose has 4 chiral centers, while fructose a ketohexose has just 3 chiral centers. Glucose has 16 stereoisomers fructose has only 8 stereoisomers The stereoisomers of monosaccharides of each carbon-chain length can be divided into two groups that differ in the conguration about the chiral center most distant from the carbonyl, carbon the reference carbon Those in which the configuration at this reference carbon is the same as that of D-glyceraldehyde are designated D isomers, and those with the same conguration as L-glyceraldehyde are L isomers. When the hydroxyl group on the reference carbon is on the right in a projection formula that has the carbonyl carbon at the top, the sugar is the D isomer; when on the left, it is the L isomer. Of the 16 possible aldohexoses, eight are D forms and eight are L. Most of the hexoses of living organisms are D isomers.( 2 )

Chiral center also exists in amino acid , with exception of glycine,almost all amino acid have L and D isomers.. The amino acid residues in protein molecules are exclusively L stereoisomers. D-Amino acid residues have been found in only a few, generally small peptides, including some peptides of bacterial cell walls and certain peptide antibiotics. It is remarkable that virtually all amino acid residues in proteins are L stereoisomers (2)

Epimers are diastereoisomers with diffrent configuration of groups around only one carbon atom. D glucose and D glactose, D glucose and D mannose, and D ribulose and D xylulose are epimer. Also D glucouronic acid and L idouronic acid are epimers

The phenomenon of optical activity encountered by Louis Pasteur in 1843, Pasteur later described the experiment and its interpretation: In isomeric bodies, the elements and the proportions in which they are combined are the same, only the arrangement of the atoms is different . . . We know, on the one hand, that the molecular arrangements of the two tartaric acids are asymmetric, and, on the other hand, that these arrangements are absolutely identical, excepting that they exhibit asymmetry in opposite directions. Are the atoms of the dextro acid grouped in the form of a right-handed spiral, or are they placed at the apex of an irregular tetrahedron ,or are they disposed according to this or that asymmetric arrangement? We do not know Now we know. X-ray crystallographic studies in 1951 conrmed that the levorotatory and dextrorotatory forms of tartaricacid are mirror images of each other at the molecular level and established the absolute configuration of each ( 2 ) Hexoses and pentoses usualy exist in solutions predominantly as cyclic rather than ring molecules. The flexibility of the chain in these monosaccharides permit the reactive carboyl group - C1 in aldoses or C2 in ketoses- to attack an internal hydroxyl at the other end of the molecule- usually C5 but also C4 - creating itramolecular hemiacetal or hemiketal. Hexoses form both pyranose rings and furanose rings ( 5 )

while pentoses form furanose rings ( 5 )

Participation of the C1 atom of aldoses and C2 atom of ketoses in cyclization reaction creats new asymetric carbon at C1 and C2 respectively and produce two possible ring structures of conformations and anomers. For example The cyclic structure is retained in solution, but isomerism occurs about position C1 the anomeric carbon to give amixture of glucopyranose (38%) and glucopyranose (62%). (4 ) conformers are isomers produced by rotation of carbon-carbon sigma bonds. For example monosaccharide of 5 or 6 carbon atoms always form ring structure This ring exist in either boat or chair forms. They are rapidly interconvertible into each other at room temperature, but the chair form is prefered in energetic terms. (5)

Substitute groups of the ring may be also of two types equatorial or axial. Axial groups are nearly vertical to the average plane of the ring, while equatorial groups are almost parallel as shown in the figure

Another conformational isomerism occur in the pentoses ribose and deoxyribose. It is puckering of the furanose ring. Four of the five atoms of the ring 3 carbons and the oxygen are in single plane the fifth atom which is either C-2 or C-3 is on either the same (above) or opposite side (below) of the plane relative to C-5. The two most common conformation for ribose ad deoxy ribose are C-2 endo and C-3 endo in which C-2 and C3 are above the plane ( 2 )

Nucleotides and nucleosides exist in a stable, non inter convertable syn and anti conformers. This is because of steric hindrance by the nitrogen base that once formed there is no freedom of rotation about the N-glycosidic bond that link pentose sugar to purine or pyrimidine. While both syn and anti conformers occurs in nature, anti conformer predominates , and it the anti conformer of nucleotides that participate in normal base pairing of double strand DNA

free rotation about the C-1_N-glycosyl bond, the different possible conformations of the deoxyribose along with rotation about the contiguous bonds that makeup the phosphosugar backbone, all reflect the structural variation in DNA. Because of steric constraints, purines in nucleotides are restricted to both the two conformations syn and anti. Pyrimidines are generally restricted to the anti conformation because of steric interference between the sugar and the carbonyl oxygen at C-2 of the pyrimidine. DNA exist in 3 frms A B and Z The B form is the most stable structure for a random-sequence DNA molecule under physiological conditions and is therefore the standard point of reference in any study of the properties of DNA ( 2 ). It is very interesting to have a look at the table enclosed

References
1-

Garrett, Reginald H./ Grisham, Charles M./ Jemiolo, David K. biochemistry 3rd edition 2005 books cole Thomson learning

23-

chemistry.tutorvista.com/organic-chemistry/isomers Nelson David L / Cox Michael M Lehninger principles of biochemistry 5th edition 2008 2 W. H. Freeman and Company Murray Robert K / Granner Daryl K / Mayes Peter A / Rodwell Victor W Harpers Biochemistry 25th ediition 1999 Mc Gram Hill Lange

4-

5-

Dow / Lindsay / Morrison Biochemistry molecules cells and the body 1st edition 1996 Addison Wesly