M.PRASAD NAIDUMSc 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 acid1. 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 MPSAs 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 BPGGlycolysis 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 2β

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 recognition1. 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

GalNAcFucose-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 glycosideUsed in cardiac insufficiency .Steroids as aglycone .Derivatives of Digitalis ,strophanthus , squill plants .Eg:-Digitonin 4Galactose +Xylulose + Digitogenin(aglycone )

OuabainInhibits 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 .