Transcript Lehninger Principles of Biochemistry 5/e

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.
R1
C
R2
O
Aldehyde is a carbonyl (C=O) where One R grp is H
Ketone is a carbonyl where No R grp is H
Terminology
Aldoses
Ketoses
D and L
Solid wedge-shaped bonds point toward the reader, dashed wedges point away.
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.
Rings
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.
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
Sugars are reducing agents
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
Glycosidic bond
Disaccharide is formed from two
monosaccharides (here, two molecules of Dglucose) 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
Amylose and glycogen
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.
Glycogen
Glycogen has the same basic
structure as amylose, but has more
branching than amylopectin.
An (α1→6) branch point of glycogen
or amylopectin
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.
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
A
Genotype
IAIA
IAi
An on RBC
A
Ab in blood
B
B
IBIB
IBi
B
A
AB
IAIB
AB
-
O
ii
-
A B
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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, Nacetyl 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.