Lecture 7Carbohydrates

Carbohydrates

They are important for ---

Formula=

Three major classes of carbohydrates:

Carbohydrates

They are important for energy storage, cell-cell signaling and cell wall structures.Most have the formula (CH2O)nThree major classes of carbohydrates: mono, oligo, poly saccharidesMonosaccharides are single sugars and can be divided into 2 groups: aldoses, which have aldehyde groups, and ketoses, which have ketone groups.

Aldehyde is a carbonyl (C=O) where One R grp is HKetone is a carbonyl where No R grp is H

R1

R2

C O

Terminology

Aldoses

Ketoses

Solid wedge-shaped bonds point toward the reader, dashed wedges point away.

D and L

Epimers

D-Glucose and two of its epimers are shown as projection formulas. Each epimer differs from D-glucose in the configuration at one chiral center (shaded pink).

Formation of hemiacetals and hemiketal

An aldehyde or ketone can react with an alcohol in a 1:1 ratio to yield a hemiacetal or hemiketal, respectively, creating a new chiral center at the carbonyl carbon. Substitution of a second alcohol molecule produces an acetal or ketal. When the second alcohol is part of another sugar molecule, the bond produced is a glycosidic bond.

In aqueous solution, monosaccharides withfive or more C atoms in the backbone occuras cyclic (ring) structures in which the carbonyl group has formed a covalent bond with the O of a hydroxyl group along the chain.These 6-membered ring compounds arecalled pyranoses.These rings form due to a general reaction that occurs between alcohols and aldehydes or ketones to form derivatives calledhemiacetals or hemiketals.Anomers are isomeric forms ofmonosaccharides that differ only in theirconfiguration about the hemiacetalor hemiketal C.

Rings

Phosphoester

Sugars are reducing agents

Oxidation of the anomeric carbon of glucose under alkaline conditions.The reaction with Cu2+ is complex, yielding a mixture of products

Oxidation is electron loss, reduction is electron gain

Reducing agent is electron donor, oxidising agent is electron acceptor.

Gain of an electron by atom/molecule is called reduction, loss of electron is oxidation.

Oxidation of the anomeric carbon of glucose under alkaline conditions.The reaction with Cu2+ is complex, yielding a mixture of products

Sugars are reducing agents

Glycosidic bond

Disaccharide is formed from two monosaccharides (here, two molecules of D-glucose) when an —OH (alcohol) of one glucose molecule (right) condenses with the intramolecular hemiacetal of the other glucose molecule (left), with elimination of H2O and formation of a glycosidic bond. The reversal of this reaction is hydrolysis—attack by H2O on the glycosidic bond. The maltose molecule, shown here as an illustration, retains a reducing hemiacetal at the C-1 not involved in the glycosidic bond. Because mutarotation interconverts the a and b forms of the hemiacetal, the bonds at this position are sometimes depicted with wavy lines, as shown here, to indicate that the structure may be either a or b.

Common Disaccharides

Polysaccharides

Polysaccharides can have one, two or many different monosaccharides

GlycogenGlycogen has the same basic structure as amylose, but has more branching than amylopectin.An (α1→6) branch point of glycogen or amylopectin

A short segment of amylose, a linear polymer of D-glucose residues in (α1→4) linkage.Amylopectin has stretches of similarly linked residues between branch points.

Amylose and glycogen

Cellulose

Human enzymes can digest a1-4 but not b1-4 glycosidic linkagesCellulase in microbes can breakdown b1-4 linkages(Ruminants have microbes in stomach)

A short segment of chitin, a homopolymer of N-acetyl-D-glucosamine units in (β1→4) linkage.

Membrane proteoglycan

Cell-extracellular interaction

Glycoproteins

Blood groups

The ABO blood group system comprises two antigens, A and B.Individuals possessing the A antigen on the surface of their red blood cells (RBCs) are said to have the A blood group. They also have anti-B antibodies in their serum.

Individuals possessing the B antigen on the surface of their RBCs are said to have the B blood group. They have anti-A antibodies in their serum.

O blood group individuals have neither A nor B antigen on their RBCs but they do possess anti-A and anti-B antibodies in their serum. They have the H antigen

AB blood group individuals have both A and B antigens on their RBCs and no antibodies in their serum.

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ABO blood groups

The Human A,B,O blood groups were discovered in 1900 by Dr. Landsteiner.

The 4 blood types were defined on the basis of a clumping reaction. Serum (the liquid part of the blood (Ab)) from one individual is mixed with red blood cells (erythrocytes) from another individual. If they belong to different groups the blood cells will clump. The clumping is due to the presence of antibodies in the serum.

Blood group Genotype An on RBC Ab in bloodA IAIA A B

IAi

B IBIB B AIBi

AB IAIB AB -

O ii - A B

A and B antigens are basically glycoproteins.

Each molecule is made up of a peptide backbone the band 3 protein, which is the anion exchange protein of the RBC membrane.

Attached to the protein from inside out are: N-acetyl galactosamine, D-galactose, N-acetyl glucosamine D-galactose

To this precursor substance is added the terminal sugar, L-fucose.

The substance thus formed is called H antigen.This H antigen is a precursor of ABO blood group antigens.

The ABO gene is located on chromosome 9.

The ABO locus has three main alleleic forms: A, B, and O.

The A allele encodes a glycosyltransferase that bonds α-N-acetylgalactosamine to D-galactose end of H antigen, producing the A antigen.

The B allele encodes a glycosyltransferase that joins α-D-galactose bonded to D-galactose end of H antigen, creating the B antigen.

In case of O allele, the exon 6 of the gene contains a deletion that results in a loss of enzymatic activity.

In case of individuals having AB blood group, two different sugars, N-acetyl galactosamine and D-galactose, are transferred to different chains of the same RBC.

There are seven exons for the ABO enzyme

Seven nucleotide substitutions distinguish the A transferase from the B transferase

One substitution is in exon 6; exon 7, the largest of all, contains the other six nucleotide substitutions.

These result in four amino acid substitutions that differentiate the A and B transferases.

Substitutions at two sites (L 266M and G268A) determine the A or B specificity of the enzyme.

This is because those two sites reside at the active site of the enzymeIn the A enzyme L and G are present in the active siteIn the B enzyme M and A are present in the active site. This results in an alteration of the shape of the active site pocket, so that a smaller size UDP-Gal, rather than UDP-GalNAc, becomes preferentially accommodated as a substrate. This change gives rise to the B specificity, or the B enzyme.