NON ENERGY ROLE OF CARBOHYDRATES

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NON ENERGY ROLE OF CARBOHYDRATES

• M.PRASAD NAIDU
• MSc MEDICALBIOCHEMISTRY,
• Ph.D. RESEARCH SCHOLAR

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

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• 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 .

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• 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
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• 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

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• ROLE IN ERYTHROCYTES
• -To maintain cell membrane integrity

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• Role in Phagocyosis

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• 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.

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• Ribonucleotide reductase
• Ribonucleotide
  Deoxyribonucleotide
• Thiroredoxine Thiroredoxine
• (Red ) (Oxi )
• NADP NADPH
  H
• 
  
• 
  HMP

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• 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

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

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• 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

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• 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 .

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• 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 .

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• 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 .

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• 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 .

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

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• 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 2ß
• 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
  .

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• Cell membrane --- Glycolipids and Glycoproteins

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• 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 .

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• 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 .

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• 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 .

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• 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

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• 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 .

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• 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

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• 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
  )

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• 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 )

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• 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 .

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• 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 .

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• 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 .

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• 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 .

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• 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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