I would feel more optimistic about a bright
future for man if he spent less time proving
that he can outwit Nature and more time
tasting her sweetness and respecting her
seniority.
—E. B. White, “Coon Tree,” 1977
Each year , 100 metric tons of CO2 is converted to Carbohydrates by plants…..
“Hydrates of Carbon”
Polyhydroxy aldehydes or ketones or compounds
which yield them on hydrolysis.
• General molecular formula Cn (H2O)n
-Some carbohydrates contain Sulphur , Nitrogen or
Phosphorus
Exceptions are acetic acid C2H4O2 and lactic acid C3H6O3 .
Rhamnose C6H12O5 is a carbohydrate
Functions of Carbohydrates
• Main sources of ENERGY in body (4kcal/g)
– RBCs and Brain cells have an absolute requirement of carbohydrates .
•
Storage form of energy (starch and glycogen)
• Excess carbohydrate is converted to fat.
• Glycoproteins and glycolipids are components of cell membranes and
receptors.
• Structural basis of many organisms .e.g . Cellulose in plants
,exoskeleton of insects , cell wall of microbes, mucopolysaccharides
and ground substance in higher organisms.
Oligosaccharide Chains Encode Biologic Information
--An enormous number of glycosidic linkages can be generated between sugars.
For example, three different hexoses may be linked to each other to form
over 1000 different trisaccharides.
--Oligosaccharide chains encode biologic information and that this depends
upon their constituent sugars, their sequences, and their linkages.
For instance, mannose 6-phosphate residues target newly synthesized
lysosomal enzymes to that organelle (see l cell disease later).
--The biologic information that sugars contain is expressed via interactions between
specific sugars, either free or in glycoconjugates, and proteins (such as lectins; see
below) or other molecules
These interactions lead to changes of cellular activity.
Carbohydrates
Monosaccharides
1 sugar unit
e.g.Glucose ,
fructose etc
Disaccharides
Oligosaccharides
2 sugar units
3-9 units
e.g.Sucrose
Polysaccharides
>10
e.g. Maltotriose
Homoglycans
Heteroglycans
e.g. starch,
glycogen
e.g. GAGs or
glycosaminoglycans
Monosaccharides
• Molecules having only one actual or potential
sugar group .
No. of
carbon
Generic name
Aldoses
Ketoses
3
trioses
Aldotriose e.g.
glyceraldehyde
Ketotriose e.g.
Dihydroxyacetone
4
tetroses
Aldotetrose e.g.
Erythrose
Ketotetrose e.g.
Erythrulose
5
pentoses
Aldopentoses e.g
Arabinose , Xylose ,
Ribose
Ketopentoses e.g.
Xylulose, Ribulose
6
hexoses
Aldohexose e.g. Glucose
, Galactose , Mannose
Ketohexose e.g. Fructose
7
heptoses
Aldoheptose:
Glucoheptose
Ketoheptose e.g
Sedoheptulose
Pentoses of Physiological importance
Hexoses of Physiological Importance
Enediol formation :•
In mild alkaline solutions, carbohydrates containing a
free sugar group (aldehyde or ketone) will
tautomerise to form enediols , where two hydroxyl
groups are attached to the double-bonded carbon
atoms .
• Since enediols are powerful reducing agents in
alkaline medium. When oxidising agents like cupric
ions are present , sugars form a mixture of carboxylic
acids by breaking at the double bonds.
BENEDICT’S AND FELHING’S TEST
BENEDICT’S REAGENT :- Sodium carbonate , copper sulphate , sodium citrate
Principle:- In alkaline medium , sugars form enediols , cupric ions are reduced ,
correspondingly the sugar is oxidized .
Reducing sugar :- Any sugar with a free aldehyde or ketone grp. is a reducing
sugar.
Clinical application :- Benedict’s test is a bed side test for detection of reducing
sugar in urine(Clinitest, Urine)
Clinitest, Urine
Benedict’s test
Procedure: - 0.5 (8 drops)ml urine + 5ml Benedict’s reagent .
Boil for 2 mins.
Interpretation:Observation
Inference
No change in colour
No sugar
Green colour
0-0.5mg%
+
Yellow
0.5-1.0mg%
++
Orange
1.0-1.5mg%
+++
1.5-2mg%
++++
Brick red
Drawback – test is not specific for glucose
Fehling’s test :- no intermediate colors are formed as because over there
a powerful reducing agent KOH is used.
Osazone formation
• All reducing sugars will form osazones with excess of phenylhydrazine
when kept at boiling temperature.
• Osazones are insoluble .
• Osazones of individual sugars have characteristic crystal from .The
differences in glucose , fructose and mannose are dependent on 1st and
2nd C & this difference is masked when Phenyhydrazine reacts with these
two carbons .
So, Glucose , Fructose and Mannose give broom shaped osazones.
Osazones –CHARACTERISTIC
STRUCTURES
Glucosazone
( broom shaped)
Maltosazone
( star shaped)
Lactosazone
(powder puff shaped)
4)Reduction to form alcohols
When treated with reducing agents such as sodium amalgam,
hydrogen can reduce sugars . Aldose yields corresponding
alcohol .Ketoses form two alcohols because of appearance of
new asymmetric carbon in this process.
E.g.
D-Glucose  D-Sorbitol  D-Fructose 
D-Mannitol
Sorbitol and Mannitol are used to identify bacterial bacterial colonies.
Mannitol is used to reduce intracranial pressure by forced diuresis.
The osmotic effect of sorbitol and dulcitol produces changes in tissues
when they accumulate in abnormal amounts. E.g cataract
Ketoses forms two alcohols because of appearance
of asymmetric carbon atoms in this process.
D-fructose
D-glucose
Galactose
Dulcitol
and
Ribose
Ribitol
Glycosides
• When the hemi-acetal group (hydroxyl grp of the anomeric C )
of a monosaccharide is condensed with an alcohol or phenol
grp , it is called as a glycoside .The non-carbohydrate grp is
called aglycone.
• Glycosides are non –reducing (WHY ?)but they may be
hydrolyzed by boiling with dilute acids.
• - glycosides are hydrolyzed by maltase from yeast , while
beta-glycosides are hydrolyzed by Emulsin from almonds .So
enzyme hydrolysis affords a method to distinguish b/w two
forms .
Some important Glycosides
Sugar
Aglycon
Glycoside
Source
Importance
Glucose
Phloretin
Phlorizin
Rose bark
Renal damage
Galactose ,
Xylose
Digitogenin
Digitonin
Leaves of
foxglove
Cardiac
stimulant
Glucose
Indoxyl
Plant indican
Leaves of
indigofera
Stain
Disaccharides
• When 2 monosaccharides are combined
together by glycosidic linkage , a disaccharide
is formed.
• Two types :Non-reducing
Sucrose
Trehalose
Cane sugar
in yeast
Reducing
Lactose
Maltose
Milk sugar
Malt sugar
•
•
•
•
•
•
Sucrose
Cane sugar, table sugar
Glu + Fru (β12)
Sweetening agent
Non-reducing
No osazones
Clinical Importance :--dental caries
--Bypasses metabolic check points- OBESITY
--“Sucrase deficiency “
Lactose
•
•
•
•
Milk sugar
Gal + Glu(β14)
Reducing
Beta glycosidic linkage
• Osazone –
Powder Puff or hedgehog shaped
Lactose Intolerance
USMLE
• Deficiency of enzyme lactase in brush border
epithelium
• Primary – only in adults , absence of a lactase
persistence allele
• Congenital- children( autosomal recessive)
• Secondary - Also common in acute gastroenteritis ,
Abdominal cramps , pain , distension and diarrhoea.
Treatment :Restriction of dairy products
Soy milk can be used for children
Maltose
•
•
•
•
2 glucose residues( 1 4 linkage)
Reducing
Malt sugar
Osazone :- Star shaped or flower petal shaped
Lactulose
• Synthetic disaccharide of Galactose and Fructose
• Poorly absorbed from the gastrointestinal tract
• Used in the treatment of hepatic encephalopathy
• Metabolized by the colonic bacteria to acidic
products CAUSES PURGATION
• Promotes the excretion of ammonia in feces as
protonated ammonium ions
HOMOGLYCAN
OR
HOMOPOLYSACCHARIDE
HETEROGLYCAN
OR
HETEROPOLYSACCHARIDE
HOMOGLYCANS
•
•
•
•
•
•
STARCH
GLYCOGEN
CELLULOSE
INULIN
DEXTRANS
CHITIN
STARCH
• Carbohydrates of the plant kingdom
• Sources :- Potatoes , tapioca, cereals (rice , wheat) and other food
grains
• Composed of AMYLOSE & AMYLOPECTIN
AMYLOSE :- When starch is treated with boiling water , 10 -20 % is
solubilized ; This part is called amylose .Contains glucose units with
-1,4 glycosidic linkages .Mol wt =400,000 or more
AMYLOPECTIN :- the insoluble part absorbs water and forms paste like
gel ; this is called as amylopectin. Amylopectin is also made up of
glucose units , but is highly branched with molecular weight more
than 1 million. The branching points are made by - 1, 6 linkage
Starch
GLYCOGEN
• Storage form of energy in animal.
• Stored in liver and muscle .
• Stores more glucose residues per gram than
starch.
• More branched and compact than starch.
• Less osmotic pressure.
• More energy in a smaller space.
 Glycogen in liver (6-8%) is higher than that in the
muscles (1-2%).
 Liver glycogen - first line of defense against declining
blood glucose levels especially between meals.
Percentage of
Tissue Weight
Tissue Body
Weight Content
Liver glycogen
5.0
1.8 kg
90 g
Muscle glycogen
0.7
35 kg
245 g
Extracellular glucose
0.1
10 L
10 g
Muscle Glycogen –only Locally available to muscles !!
A homopolysaccharide - linear chain of (1→4) linked
glucosyl residues with branches joined by  (1→6) linkages
INULIN
• D -fructose chain in -1,2 linkages.
• Source :- bulbs and tubers chicory, dahlia,
dandelion, onions, garlic.
• Not metabolized .
• Not absorbed nor secreted by kidneys.
• USE – to measure GFR.
DEXTRANS
• Highly branched homoglycan containing Glu residues in 1-6, 1-4 and
1-3 linkages.
• Produced by microbes.
• Mol. wt :- 1-4 million.
• Colloidal solution, Low osmotic effects, slow disintegration and
utilization, slow elimination from the body
• As large sized , they will not move out of vascular compartment so
used as plasma expanders.
• In hypovolemic shock, given intravenously increases blood volume.
Mucopolysaccharides or GAG
--- [ URONIC ACID + AMINO SUGAR]---n
Acetylated amino sugars, sulfate and carboxyl groups may also be present
Amino sugars
• Amino grps. may be substituted for hydroxyl grps of sugars to give rise to
amino sugar.
• Generally the grp is added to the second C of hexoses.
• They are non –reducing and do not form osazones
• They are found in GAGS , glycoproteins , proteoglycans
• Abbreviations :GluNac = N-acetyl –glucosamine
GalNac =N-acetyl-galactosamine
GLUCOSAMINE or 2 amino-D-glucopyranose (α
form)
• The amino group may be further acetylated to produce Nacetlyated sugars like N-acetly glucosamine (GlcNac) or Nacetyl galactosamine(GalNac) which are important
constituents of glycoproteins and MPS
Chondroitin sulfate
• Most abundant
• glucuronic acid +
N-acetyl galactosamine
sulfate
• Found in cartilage, tendon,
ligament.
• provides much of the
resistance of cartilage to
compression.
Dermatan sulfate
• Wide distribution in
ECM
• Iduronic acid + N-actyl
galactosamine sulfate.
• Helps in wound repair
and fibrosis.
Keratan sulfate
• N-acetyl glucosamine
and galactose
• Absence of glucuronic
acid.
• Very heterogenous
molecules – have
additional groups –
NANA, mannose etc.
•
KSI –CORNEA
• KS II – Loose connective
tissue
Heparin
• Sulfated iduronic acid +
sulfated glucosamine
• Found in mast cells
• Acts as an
anticoagulantbinds
antithrombin III and
activates it
Heparan sulfate
Hyaluronic acid
• Glucuronic acid +
Glucosamine
• glucuronic acid + N-acetyl
glucosamine
• They are acetylated
compared to heparin.
• Not sulfated
• Found in basement
membrane and cell
surface, Skin fibroblasts
and aortic walls
• Not linked to any protein
• Found in synovial fluid of
joints, vitreous humor of
eye.
Relationship between GAG structure and
function
• strong negative charges -- > ( POLYANIONS )
(-COO- and -OSO3-) cause molecule to fan
outwards and repel adjacent molecules
• Surrounded by a shell of hydration.
• Slippery consistency – similar to magnets.
• Act like cushions – compressible but spring
back after the pressure is removed (sponge
effect).
RESILIENCE of GAGS
• reversible compressibility accounts for
resilience of synovial fluid and vitreous humor
of eye.
Some Functions of
Glycosaminoglycans and Proteoglycans
 Act as structural components of the ECM
 Have specific interactions with collagen, elastin, fibronectin,
laminin, and other proteins such as growth factors
 As polyanions, bind polycations and cations
 Contribute to the characteristic turgor of various tissues
 Act as sieves in the ECM
 Facilitate cell migration (HA)

contd..
Functions of Glycosaminoglycans and Proteoglycans
contd..
 Have role in compressibility of cartilage in weight-bearing (HA,
CS)
 Play role in corneal transparency (KS I and DS)
 Have structural role in sclera (DS)
 Act as anticoagulant (heparin)
 Are components of plasma membranes, where they may act as
receptors and participate in cell adhesion and cell-cell interactions
(eg, HS)
 Determine charge-selectiveness of renal glomerulus (HS)
 Are components of synaptic and other vesicles (eg, HS)
Interactions b/w various Proteoglycans
(Membrane protein)
(extracellular protein)
Harper’s Illustrated Biochemistry 28th edition
Proteoglycans
• Proteoglycans are proteins that contain covalently linked
glycosaminoglycans. ( GAGS 95 % PROTEINS 5% approx.)
• E.g. Syndecan,betaglycan, serglycin, perlecan, aggrecan,
versican,decorin, biglycan, and fibromodulin.
• They vary in tissue distribution, nature of the core protein, attached
glycosaminoglycans, and function.
• The proteins bound covalently to glycosaminoglycans are called
“core proteins”
• The amount of carbohydrate in a proteoglycan
is usually much greater than is found in a glycoprotein
and may comprise up to 95% of its weight.
Darkfield electron
micrograph of a
proteoglycan aggregate
• Bottle brush appearance
Schematic representation of the proteoglycan
Aggrecan
Core
proteins
are
covalently
attached to
GAGs
Link
Proteins
mediate
the core
protein
hyaluronate
interaction
Glycoproteins
• Glycoproteins have one or several oligosaccharides of varying
complexity joined covalently to a protein.
• They are found on the outer face of the plasma membrane, in the
extracellular matrix, and in the blood.
• Inside cells they are found in specific organelles such as Golgi
complexes, secretory granules, and lysosomes.
• The oligosaccharide portions of glycoproteins are less monotonous
than the glycosaminoglycan chains of proteoglycans ; they are rich
in information, forming highly specific sites for recognition and
high-affinity binding by other proteins.
Proteoglycans
Glycoproteins
• Mainly carbohydrates 85%
with 15 percent protein.
• Mainly protein with
minimal carbohydrates
• Composed of REPEATING
units –
heteropolysaccharide
• Composed of varying
monosaccharide units.
• Carbohydrates are linear
with more than 50 sugar
units
• Carbohydrates are
branched with 3-10 sugar
units.
There are 3 major classes of
glycoproteins
1. those containing an O-glycosidic linkage (ie,O-linked),
involving the hydroxyl side chain of serine or
threonine and a sugar such as N-acetylgalactosamine
(GalNAc-Ser[Thr])
2. those containing an N-glycosidic linkage (ie, N-linked),
involving the amide nitrogen of asparagine and Nacetylglucosamine (GlcNAc- Asn)
3. Glycosylphosphatidylinositol-anchored (GPIanchored, or GPIlinked) glycoprotein
Glycolipids
• Glycolipids are membrane lipids in which the
hydrophilic head groups are oligosaccharides,
which, as in glycoproteins, act as specific sites
for recognition by carbohydrate- binding
proteins
Degradation of GAGs:
• Degraded by lysosomes.
• Enzymes – acid hydrolases.
• Extracelluar GAGs are brought inside
by phagocytosis.
Lysosomal storage disorders:
• LSDs are a group of about 40 rare inherited
disorders that are characterized by lysosomal
dysfunction leading to abnormal accumulations
of substances inside of lysosomes.
• Disorders are usually caused by the deficiency
of one of the Lysosomal enzyme.
Classification:
• MAIN GROUPS :– Mucopolysaccharidoses
– Mucolipidoses
– Sphingolipidoses
• Others :– Pompe’s disease (Glycogen storage disorder
type II)
– Wolman disease( Lysosomal acid lipase deficiency)
Mucopolysaccharidoses
Mucopolysaccharidoses are a group of hereditary disorders of proteoglycan
metabolism that are characterized by excessive intralysosomal accumulation of GAGs in
various tissues.
Summary of the Major Features of the
Mucopolysaccharidoses
• They exhibit a chronic progressive course.
• They affect a number of organ systems (ie, they are multisystem
disorders).
• Many patients exhibit organomegaly (eg, hepato- and splenomegaly may
be present).
• Patients often exhibit dysostosis multiplex (characterized by severe
abnormalities in the development of cartilage and bone, and also mental
retardation).
• Patients often exhibit abnormal facies (facial appearance).
• Other signs sometimes found are abnormalities of hearing, of vision, of
the cardiovascular system, and of mental development.
USMLE
Hurler syndrome: MPS-1
• Enzyme def: α-L – Iduronidase
• Accumulation : Heparan and Dermatan sulfate
• Key features: corneal clouding, mental retardation,
micrognathia, coarsening of facial features with
macroglossia, inguinal and abdominal hernias, retinal
degeneration.
• Death due to accumulation in coronary arteries.
• Can be treated before 18 months – BM transplant.
USMLE
Hunter syndrome: MPS-II
• Enzyme defect : Iduronate sulfatase.
• Only X-linked MPS.
• Similar to hurler – but milder, no corneal clouding
• Variable mental retardation.
• Accumulation – Heparan and Dermatan sulfate
.
I cell disease
USMLE
• I-cell disease is an inherited lysosomal storage disorder.
– One unique feature of this disease is the presence of phase-dense
intracytoplasmic inclusions in the fibroblasts of patients.
– These cells were termed inclusion cells, or I-cells; thus, the disease
was designated I-cell disease.
• The biochemical defect in I-cell disease involves the first step in the
addition of the mannose-6-phosphate moiety.
• This is because of a deficiency of golgi associated
phosphotransferase.
•
It is classified this disease as mucolipidosis type II (ML II) because it
had clinical characteristics that included mucopolysaccharidoses
and sphingolipidoses.
Some Laboratory Tests Used in the Diagnosis of a
Mucopolysaccharidosis

Urinalysis for presence of increased amounts of GAGs.

Assays of suspected enzymes in white blood cells, fibroblasts or
possibly serum.

Tissue biopsy with subsequent analysis of GAGs by electrophoresis.

Use of specific gene tests.

Prenatal diagnosis can now be performed in at least certain cases using
amniotic fluid cells or chorionic villus biopsy.
A 30-month-old child presents with coarse facial features, corneal
clouding, hepatosplenomegaly, and exhibiting disproportionate shorttrunk dwarfism. Radiographic analysis indicates enlargement of the
diaphyses of the long bones and irregular metaphyses, along with
poorly developed epiphyseal centers. Other skeletal abnormalities
typify the features comprising dystosis multiplex. The child’s physical
stature and the analysis of bone development indicate the child is
suffering from which of the following disorders?
(A) Hunter syndrome
(B) Hurler syndrome
(C) Maroteaux-Lamy syndrome
(D) Morquio syndrome type B
(E) Sanfilippo disease type A