Transcript CARBOHYDRATE CHEMISTRY and MTABOLISM Mohamed Aly Abdelhafez, PhD By

CARBOHYDRATE CHEMISTRY
and MTABOLISM
By
Mohamed Aly Abdelhafez, PhD
Medical Biochemistry & Molecular Biology Department
Faculty of Medicine, Cairo University
Definition
• Carbohydrates Chemically, they are polyhydroxy
aldehydes or ketones.
• Carbohydrates have the following biological
functions:
• 1- Chief source of energy (50-60%) of daily
requirement.
• 2- Partners of cell organelles and intercellular
matrix structure, in complex with protein (as
glycoprotein or proteoglycans), or with lipids (as
cerebrosides or gangliosides).
• 4- Interconvert with some amino acids and lipid
derivatives in
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intermediary metabolic pathways.
Classification
• The basic unit is monosaccharide (mono= single or one) or simple sugar.
Structurally monosaccharides contain
carbon and water elements (hydrogen and
oxygen).
• Oligosaccharides (oligo- = few) are
containing 2-10 monosaccharide units.
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If more than 10 monosaccharide units it
is polysaccharide(poly-= many).
Monosaccharides
• Monosaccharides are water-soluble sweet carbohydrates.
• They are classified into: a) aldoses e.g.glucose , galactose ,
mannose, and b) ketoses e.g. fructose.
• Each class is further subclassified according to number of carbon
atoms per molecule of monosaccharide into: Triose (C3) , tetrose
(C4) ,pentose (C5) as ribose ,hexose (C6) as glucose ,galactose
,fructose ,as well as mannose ; and heptose (C7) .
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CHO
HCOH
HOCH
HCOH
HCOH
CH2OH
Glucose
CHO
CH2OH
HCOH
C=O
HOCH
OHCH
HOCH
HCOH
HCOH
HCOH
CH2OH
CH2OH
Galactose
Fructose
HEXOSES
CHO
CHO
HCOH
HCH
HCOH
HCOH
HCOH
HCOH
CH2OH CH2OH
Ribose Deoxyribose
PENTOSES
Monosaccharide derivatives
• a- Deoxy-sugar, in which C-2 is devoid of oxygen, e.g.
deoxyribose.
• b- Sugar alcohol, in which the carbonyl group (aldehyde
or ketone) are reduced into alcoholic group.
• c- Amino-sugar, e.g. glucosamine.
• d- Aminosugar acid, the aminosugar is linked to pyruvic
or lactic acid, neuraminic acid.
• e- Uronic acid, the terminal -OH group of C-6 is oxidized
to –COOH,e.g. glucuronic acid.
• f- Aldonic acid, the aldehyde group of C-1 is oxidized to COOH, e.g. gluconic acid
• g- Aldaric acid, both the -OH of terminal carbon and CHO of C-1 are oxidized to -COOH, e,g. Glucaric acid.
Cyclic Configuration
The cyclic configuration may be in a vertical or a
horizontal ring. In either condition it is 5-C ring
that is closed with oxygen bridge, called
pyranose.
• A 4-C ring with oxygen bridge is another form
called furanose. All forms are inter-changeable.
• Essentially the carbonyl group should be
involved in formation of oxygen bridge. It is the
anomeric carbon.
• As the ring is formed the anomeric carbon
becomes asymmetric carbon.
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Cyclic Configuration
• According to the position of OH – group the sugar is
α – or β- .
• The α – sugar of vertical assigned ring, the OHgroup is oriented on the right of the anomeric carbon
but in horizontal ring the orientation this OH is below
the plane of the ring. Vice versa for β-sugar.
• Similarly all carbons involved in the ring formation;
i.e., what's on the right of the straight chain is below
the plane of the horizontal ring. An exception is
4th.C in furanose and 5th. C in pyranose structure
because of rotation associated with ring closure.
Properties of monosuccharides
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Optical activity:
The optically active compound contains at least one
asymmetric carbon atom (the four valances are
satisfied by four different atoms or groups.
The plane-polarized light (PPL) is that passed through
a calcite (CaCO3) prism. The vibrations of the
electromagnetic waves are unified in one plane instead
of being in three perpendicular planes.
As PPL passes through an optically active material it
deviates either in clock-wise direction (right-handed or
dextrorotation, signed "+" ) or anti-clock-wise direction
(left-handed or levorotatory, signed "-" ) .
Deviation of light path depends on the number of
asymmetric carbons per molecule.
Optical activity
• Glucose is dextrorotatory, it is called dextrose , whereas
fructose is levorotatory , levulose.
• Specific angle of rotation; considering the pH,
concentration , temperature , and other dissolved
materials in solution.
• The angle of rotation value is preceded by the symbol
(+) or (-) depending on the direction of rotation. The
angle is measured by an instrument called
Polarisoscope or Polarimeter.
• D- or-L sugar depends on orientation of the -OH group
in the penultimate carbon atom, assuming the aldehyde
or ketonic group is oriented "up“. Right handed position
of this –OH, the sugar is in D- form, whereas left-sided
position it is in L- form.
Optical activity
• D- and L- nomination does not indicate the direction of
rotation of the PPL.
• α- and β- are so.
• Mutarotation, (change of the specific angle of rotation of
a recently prepared sugar solution). Although both αand β- are in the same direction of rotation of PPL, yet
they have different values.
• The D- sugar is a mirror image of the L-form of the same
sugar , both are called enantiomorphs , antimers , or
stereo-isomers. Both have the same specific angle of
rotation but on reversed direction.
Optical activity
• Other form of isomerism is the similarity in number and
distribution of groups around the asymmetric carbon
except one carbon ; e.g., glucose and galactose are
aldohexoses identical in structure except the -OH
attached to C-4 is on the right-side in glucose and on the
left-side in galactose. Both sugars are epimers in C-4.
• If an equimolar amount of the D-form and L-form of the
same sugar are mixed together, they will lose their
optical activity, i.e. no deviation of PPL as it passes
through this mixture. The mixture of this character is
called racemic mixture. Deviation of light path to either
side by the D- form is corrected by the other form by the
same angle but on the other side.
Other monosacchride properties
• monosaccharides are reducing agents in alkaline media
.Cupric ions of Fehling or Benedicts solutions
• Monosacchrides can be oxidized into the corresponding
aldonic, uronic or aldaric acids (in vitro ) depending on
the strength
• Glucose is oxidized to gluconic acid, glucuronic acid
or to glucaric (saccharic acid). Galactose is similarly
oxidized to mucic acid.
• Monosaccharides are reduced to the corresponding
alcohol; i.e. glucose to sorbitol.
• The primary alcoholic group of C1 or terminal carbon
can be esterified by phosphorylation. Glucose-6phosphate, fructose-1-phosphate and ribulose-5phosphate are examples.
Oligosaccharides
• Oligosaccharides are two-monosaccharide units per
molecule. The units are joined together with a glycosidic
bond.
• Glycosidic bond binds the carbonyl group of one
molecular unit with either an alcoholic group of C-4 of the
other unit (as in lactose and maltose), or with the
carbonyl group of the other unit (as in sucrose). In the
latter occasion the sugar loses the properties due to the
free carbonyl group as reduction of metallic ions and
interchange of the α- and β- forms.
• Disaccharides are oligosaccharides containing two
monosaccharide residues.
• Lactose is the milk sugar. It is composed of glucose and
galactose moles linked by β-glycosidic bond .
Oligosaccharides
• Maltose is barely sugar made of two moles of glucose
linked by α-glucosidic bond. Sucrose is cane sugar that
is made of one mole of glucose and another of fructose
linked by β-glycosidic linkage.
• Hydrolysis of the disaccharide to the parent
monosaccharides changes the angle of rotation of PPL.
In case of sucrose the change affects the angle
magnitude and direction. Sucrose is dextrorotatory, on
hydrolysis whether enzymatic or acidic, the hydolysate is
inverted into strong levoroitatory mixture of glucose and
fructose. Hence, sucrose is known as invert sugar and
sucrase, the enzyme hydrlysing sucrose, is called
invertase.
Polysaccharides
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Carbohydrates containing 10 or more monosacchride units per
molecule.
• If the monosaccharide unit is of one-type, it is homopolysaccharide
(both starch and glycogen are made of hundreds of glucose units,
glucosans or glucans) . Dextrin, is similar to starch but of fewer
glucosyl units, lower molecular weight and it is less branched.
Cellulose is another homopolysaccharide but cannot be digested in
human gastrointestinal tract (GIT) due to absence of the specific
digesting enzyme (β-glucosidase).
• Starch is plant in origin. It is a mixture of amylopectin (branchedchain glucosan, represents 80-90 % of starch molecule) and
amylose (straight-chain glucosan represents 10–20 % of starch
mole).
• Acid hydrolysis of starch results in mixture of dextrins of different
molecular weights, maltose and free glucose depending on the pH,
temperature, and duration of hydrolysis process.
Polysaccarides
• Glycogen is of animal origin. It is similar in structure to
amylopectin but more highly branched.
• Inulin is a plant fructosan that is not digested and thus
unutilizable. It is present in garlic ,onion and artichoke.
• Agar is sulfated galactosan present in sea-weeds. It
makes gels and sols depending on the prevailing
temperature and concentration. It is used in preparation
of bacterial cultures in the clinical laboratory.
• Pectins are sugar-acid polymers. They are present in
citrus fruits, apple, carrots and beets. They make a jellylike substance when soluble in water. They have
pharmaceutical and food industrial applications.
• Gum acacia and gum Arabic are homo-polysaccharides
that, also have pharmaceutical and industrial uses.
Hetero-polysaccarides
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Heteropolysaccharides are glucosaminoglycans
(GAGS), or mucopolysaccharides.
complex macromolecules, repetitive units of
disaccharides
A monomer consists of uronic acid (D-glucuronic acid or
its C-5 epimer L-iduronic acid) and amino
sugar(hexosamines as glucosamine or galactosamine).
They are either sulfate-free as hyaluronic acid (Nacetylglucosamine +glucuronic acid) or
sulfated glucosaminoglycans as: heparine ,
chondroitin sulfate , dermatan sulfate and heparan
sulfate.
NCH2
O
Monosaccharide
Repeated monomeric units
Linkage region
Core proteine
-C
Krebs’ Cycle (Tricarboxylic acid cycle,TCA)
Acetyl CoA
oxaloacetate
2 CO2
3 (NADH+H+)
FADH2
Succinate
GTP
GDP
Succinyl CoA
Intermediates
Citric acid
Glycogen metabolism
Glycogenesis
Glycogen
Glucose-6-P
Liver,Kid.
Glucose
Glycogenolysis
Lipogenesis
Triacylglycerol
G-6-P
Glycerol-3-P
fatty acids
( glycolysis )
acetyl CoA
pyruvate
oxaloacetate
Cytoplasm
Mitochondria
Citrate
Acetyl CoA
Oxaloacetate
KREBS’ CYCLE