Lecture 7 Carbohydrates

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)n Three major classes of carbohydrates: mono, oligo, poly saccharides Monosaccharides 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 H Ketone 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 with five or more C atoms in the backbone occur as 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 are called pyranoses. These rings form due to a general reaction that occurs between alcohols and aldehydes or ketones to form derivatives called hemiacetals or hemiketals. Anomers are isomeric forms of monosaccharides that differ only in their configuration about the hemiacetal or hemiketal C. Rings

Phosphoester

Sugars are reducing agents Oxidation of the anomeric carbon of glucose under alkaline conditions. The reaction with Cu 2+ 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 Cu 2+ 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 H 2 O and formation of a glycosidic bond. The reversal of this reaction is hydrolysis— attack by H 2 O 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

Glycogen Glycogen 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 linkages Cellulase 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.

61 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 RBCAb in blood AIAIA A  B IAi B IBIBB  A IBi ABIAIBAB- Oii -  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. band 3 protein 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.glycosyltransferaseN-acetylgalactosamine 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 enzyme In the A enzyme L and G are present in the active site In 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.