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PRASAD NAIDU
MSc MEDICALBIOCHEMISTRY,
Ph.D. RESEARCH SCHOLAR
Definition
Carbohydrates are polyhydroxy aldehydes or ketones or their
derivatives .
Digested Absorbed
Diet Monosaccharide Portal
circulation
Enters
systemic Glucose Liver
circulation Enters Converted
Mainly meant for energy .
There are other special functions of this molecule .
FATE OF GLUCOSE & ITS UTILISATION
OXIDATION STORAGE LIPOGENESIS CONVERSION CONVERSION
-GLYCOLYSIS GLYCOGEN INTO AMINO INTO OTHER
-HMP SHUNT ACIDS CARBOHYDRATES
-URONIC ACID
PATHWAY
-RAPOPORT
LUEBERING
CYCLE
GLUCOSE
HEXOSE MONO PHOSPHATE (HMP) SHUNT
Alternate oxidative pathway for GLUCOSE
Mainly meant for production of NADPH and PENTOSE
SUGARS
Occurs in special tissues for special function eg :- Liver, RBC,
Adrenal cortex, Lactating mammary gland.
1. NADPH
Used as electron donor in many reductive synthesis in the
body .
eg:- -Extra mitochondrial de novo fatty acid synthesis.
-Synthesis of Cholesterol
- To keep Glutathione in reduced state ( RBC, Lens)
-Phagocytosis
ROLE IN ERYTHROCYTES
-To maintain cell membrane integrity
Role in Phagocyosis
Role of HMP pathway in Lens
10% of glucose is oxidized in this pathway to
produce NADPH to keep G-SH in reduced form
,which is necessary for maintenance of lens
proteins.
Ribonucleotide reductase
Ribonucleotide Deoxyribonucleotide
Thiroredoxine Thiroredoxine
(Red ) (Oxi )
NADP NADPH + H
+
HMP
2. TO PROVIDE PENTOSE
For Nucleotide and Nucleic acid synthesis
In denovo synthesis , purines are built on R-5-P
molecule to form nucleotides .
Component of important molecules like ATP ,ADP,
cAMP ,cGMP
and co enzymes like NAD, NADP ,FMN , FAD . CoA
Uronic acid pathway
Biomedical importance
Production of D-Glucuronic acid ------mainly utilised
for detoxification of foreign substances
(Xenobiotics)
----also used for synthesis of MPS
Functions of Glucuronic acid
1. Conjugation
UDP Glucuronic acid is a active form
Conjugation takes place in liver & enzyme which
catalises is Glucuronyl transferase
various Xenobiotics like drugs ,chemicals ,
pollutants ,food additives , carcinogens &
endogeneous hormones . are converted into
corresponding Glucuronides which are more polar
& soluble , excreted in urine .
Eg :- Bile pigments (bilirubin )mono &
diglucuronoides
Aromatic amino acids -----Benzoic acid
Drugs & other xenobiotics------ First hydroxylated by
mono oxygenase Cyt P450 system & then conjugated
with D-Glucuronic acid .
Hormones-----Thyroid hormones ,derivatives of certain
steroid hormones are detoxified by D-Glucuronic acid
.
2. Synthesis of MPS
-composed of amino sugars and uronic acid .
-amino sugar may be glucosamine or galactosamine
which is acetylated .
-uronic acid may be D-glucuronic acid or L-iduronic
acid
-some may contain only galactose with glucosamine
Eg:- Hyaluronic acid , Chondroitin sulphate ,Keratan
sulphate , Heparin .
Functions of MPS
As a constituents of extra cellular matrix interacts
with collagens and elastins
Acts as polyanions ---binds to polycations and
cations (Na+, K+ ) ,thus attracts water by osmotic
pressure into extra cellular matrix contributing to
its turgor .
Acts as a barrier in tissues ---Hyaluronic acid
permits metabolites to pass through but resists
penetration of bacteria and other infective agents
.Also acts as lubricant and shock absorber .
Heparin acts as a anticoagulant and also as co-
enzyme for Lipoprotein lipase enzyme
Dermatan sulphate present in sclera of the eye
maintains the overall shape of the eye .
Keratan sulphate present in cornea of the eye and
lie between the collagen fibrils and play an
important role in maintaining corneal transperancy
.
Rapoport Leubering cycle in RBC
mutase
1,3 BPG
SLP 2,3 BPG
Glycolysis ATP
phosphatase
3PG
Functions of 2,3 BPG
2,3 BPG is the most abundant organic phosphate in
RBC ,where its concentration is roughly equals to that
of Hb
One molecule of 2,3 BPG binds to a pocket in the
center of the deoxy Hb tetramer ,formed by the 2
globin chains .
This preferrential binding stabilises the taut form.
This reduces the affinity of Hb for oxygen thus
enables Hb to release oxygen at tissue level .
Cell membrane --- Glycolipids and Glycoproteins
Glycoproteins
Located on the extracellular side of plasma membrane
2%-10%------are contributed by the sugar residues
of their glcoproteins
Membrane bound glycoproteins participate in a broad
range of cellular phenomena including cell surface
recognition , cell adhesion , blood group antigens .
GLYCOPHORINS
Transmembrane protein with carbohydrate coat .
Single polypeptide chain with 16 attached
oligosaccharide units .
These carbohydrate units are rich in sialic acid a
negatively charged sugar .
The carbohydrate units of glycophorins give RBC a
very hydrophilic , anionic coat , which enables them
to circulate with out adhering to other cells and vessel
walls .
Cell-Cell recognition
1. Eg:- Asialoglycoprotein receptor
Many newly synthesized glycoprotein , such as
immunoglobulin , peptide hormones contain
carbohydrate units with sialic acid residues .
In course of hours or days ,depending upon the
particular protein, these groups are removed by
SIALASES protruding from the surface of blood
vessels .
The exposed galactose residues from the trimmed
glycoprotein is detected by
ASIALOGLYCOPROTEIN RECEPTOR in the
plasma membrane of the liver cells .
The complex of the glycoprotein and receptor is
then internalised by the liver cells
ABO Substances
These are glycosphingolipids and glycoproteins
sharing common oligosaccharide chains .
On RBC membrane oligosaccharide that determines
the specific nature of ABO substance is present in
glycosphingolipid .
In secretions ----the same oligosaccharide is present in
glycoprotein .
H substance is the biosynthetic precursor of both A
and B substance .
Fucose -Gal-GlaNAc-R
A
GalNAc
Fucose-Gal-GlaNAc-R
H
Fucose-Gal-GlaNAc
B
Gal
Glycosides
Glycosides are formed when hemiacetal or hemiketal
hydroxyl group ( of anomeric carbon ) of a carbohydrate
reacts with a hydroxyl group of another carbohydrate or a
non carbohydrate ( aglycone )
Aglycone can be ---methanol , glycerol , sterol , phenol , or
bases like adenine .
They are important in medicine due to their action on
cardiac muscle . ( steroids as aglycone )
Cardiac glycoside
Used in cardiac insufficiency .
Steroids as aglycone .
Derivatives of Digitalis ,strophanthus , squill plants .
Eg:-Digitonin 4Galactose +Xylulose +
Digitogenin(aglycone )
Ouabain
Inhibits active transport of Na+ in cardiac muscle
(sodium pump inhibitor )
Sucrose
If introduced parentally cannot be utilised , but changes
osmotic condition of the blood and causes a flow of water
from the tissue into the blood .
Thus can be used in edema like cerebral edema .
Homopolysaccharides
Inulin
-polymer of D Fructose .
-Used in renal function test to determine GFR .
Cellulose
-polymer of D Glucose .
-not digested in humans .
-adds bulk to the intestinal substance and stimulate
peristalsis and elimination of indigested food
residues .
Dextrins
- partial hydrolysed product of starch .
- used as mucilages .
Dextrans
- polymer of D Glucose ( alpha 1-6 ,1-4 , 1-3
linkages in each unit )
-molecular weight 75000
-used as plasma expander due to their high
viscosity , low osmotic pressure, slow disintegration,
utilisation and elimination .
Agar
-made up of repeated units of Galactose which is
sulphated .
-purified agar dissolves in hot water and on cooling it
sets like a gel which is used in agar plates for culture
of bacteria .
Agarose
-Galactose combined with 3,6 anhydro galactose
units
-used as a support medium in Electrophoresis .
Conversion into aminoacids
Synthesis of non essential amino acidsby
transamination reaction .
Eg:-pyruvate alanine
oxaloacetate aspartate
C skeletons of nonessential aminoacids are derived
from glucose or its metabolites .