NON ENERGY ROLE OF CARBOHYDRATES

1. NON ENERGY ROLE OF CARBOHYDRATES M.PRASAD NAIDU MSc MEDICALBIOCHEMISTRY, Ph.D. RESEARCH SCHOLAR

2. Definition Carbohydrates are polyhydroxy aldehydes or ketones or their derivatives .

3. Digested Absorbed Diet MonosaccharidePortal circulation Enters systemicGlucose Liver circulationEntersConverted Mainly meant for energy . There are other special functions of this molecule .

4. GLUCOSE 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

5. 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. • 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

6. ROLE IN ERYTHROCYTES -To maintain cell membrane integrity

7. Role in Phagocyosis

8. 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.

9. Ribonucleotide reductase Ribonucleotide Deoxyribonucleotide Thiroredoxine Thiroredoxine (Red ) (Oxi ) NADP NADPH + H+ HMP

10. 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

11. Uronic acid pathway Biomedical importance Production of D-Glucuronic acid ------mainly utilised for detoxification of foreign substances (Xenobiotics) ----also used for synthesis of MPS

12. Functions of Glucuronic acid • 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

13. 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 .

14. 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 .

15. 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 .

16. 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 .

17. Rapoport Leubering cycle in RBC mutase 1,3 BPG SLP 2,3 BPG Glycolysis ATP phosphatase 3PG

18. 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 .

19. Cell membrane --- Glycolipids and Glycoproteins

20. 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 .

21. 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 .

22. Cell-Cell recognition • 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 .

24. 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

25. 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 .

26. 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

27. 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 )

28. 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 )

29. 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 .

30. 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 peristalsisand elimination of indigested food residues .

31. 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 .

32. 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 .

33. 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 .

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