what is glyacation. how glyacated product affect our body. how these are produced. prevention and control.

1. GLYCATION
MOHD SALMAN
2017MBT013
MSc. FINAL

2. WHAT IS GLYCATION?
• Glycation is the result of the covalent bonding of a sugar
molecule, such as glucose or fructose, to a protein or lipid
molecule, without the controlling action of an enzyme.
• Glycation may occur either inside the body (endogenous glycation)
or outside the body (exogenous glycation)
• It is a haphazard process that impairs the functioning of
biomolecules, and does not require the expenditure of ATP.

3. EXOGENOUS GLYCATION
• Referred to as dietary or pre-formed.
• are formed when sugars are cooked with proteins or fats,
Temperature over 120 °C (~248 °F) greatly accelerate the
reactions.
• may also contribute to the formation of acrylamide, a potential
carcinogen, during cooking.

4. ENDOGENOUS GLYCATION
• occur mainly in the bloodstream to a small proportion of the
absorbed simple sugars: glucose, fructose, and galactose.
• fructose has approximately ten times the glycation activity of
glucose
• Glycation is the first step in the evolution of these molecules
through a complex series of very slow reactions in the body known
as Amadori reactions and Schiff base reactions. which lead to
advanced glycation end-products (AGEs)

5. ADVANCED GLYCATION END PRODUCTS
• AGEs are modification of protein, lipid and nucleic acid that
become glycated and Oxidized after contact with reducing sugars.
• Further glycation of proteins and lipids causes molecular
rearrangements that forms AGEs

6. AGEs BIOCHEMISTRY
• FACTORS CRUCIAL FOR AGEs
1. The rate of turnover of proteins for glycoxidation.
2. The degree of hyperglycemia.
3. Extent of oxidation stress in environment

7. GLUCOSE NH2-PROTEIN GLUCOSE NH-PROTEIN
SCHIFF BASE
KETO-AMINE AMADORI
PRODUCT
GLUCOSE NH-PROTEIN
REARRANGEMENT
PROTEIN AGEsAGEs
PROTEIN CROSSLINKING
AGEs FORMATION

9. RECEPTOR FOR AGEs
• A member of immunoglobulin super family of receptors.
• Human RAGE gene present on chromosome no. 6 in the major
histocompatibility complex between the genes of class 2 and
class 3.
• (NF)-κB sites, an interferon-γ response element, and an NF-
interleukin-6 (IL-6) DNA binding motif are located on RAGE
promoter.

10. • RAGE is upregulated when AGE Ligands accumulate :
POSITIVE-FEEDBACK ACTIVATION.
• Upregulation occurs on endothelial cells, smooth muscle
cells, and mononuclear phagocytes in diabetic
vasculature.
• Other receptors: AGE-R1(Oligosaccharyl transferase-48),
AGE-R2(80K-H phosphoprotein) and –R3(galectin-3) and
the class A macrophage scavenger receptor types 1 and
2.

12. EFFECT OF AGES
•ON EXTRACELLULAR FUNCTION :
Alteration of properties of the matrix
proteins COLLAGEN, VITRONECTIN, and LAMININ
through AGE-AGE intermolecular covalent bonds,
or cross-linking.

13. EFFECT OF AGES
•ON INTRACELLULAR FUNCTION:
Rate of AGEs formation on intracellular proteins
is slowest in the presence of glucose and more rapid
with natural sugars fructose, glyceraldehyde-3-
phosphate and glucose-6-phosphate.
Fibroblast growth factor is glycated reducing the
mitogenic activity of endothelial cell cytosol by 70%.

14. EFFECT OF AGEs
•ON ENDOTHELIAL CELL:
AGEs are chemotactic for human blood monocytes both in
vitro and in vivo.
AGEs on the subendothelium induce monocyte migration
across an endothelial cell monolayer.
AGE-bound RAGE on the endothelium alters cell surface
structure, from that of an anticoagulant to a procoagulant
endothelium, via reduced thrombomodulin activity concomitant with
increased tissue factor expression.

15. EFFECT OF AGEs
•EFFECTS ON NO(NITRIC OXIDE) :
AGEs reduce the bioavailability and activity
of endothelium derived NO.
Impaired vasodilation in diabetes may be a
result of AGEs reduction of NO activity.
AGE- bound RAGE in endothelium produces
reactive oxygen intermediates triggered through the
activation of NADPH oxidase.
ROS activate NF-κB too.

16. DISEASES
• DIABITIES
• ATHERIOSCLROSIS
• NEURODEGENERATIVE
• SKIN AGING
• CANCER
• ALZHIEMERS DISEASE

17. PREVENTIONS
• NATURAL PREVENTION
By physical exercise
• THROUGH DIETARY PRODUCTS
by the use of juicy fruits eg: lemon.
liquid foods eg: soup.

18. ANTI-AGE STRATIGIES
1. Substance preventing or inhibiting AGE formation:
Aminoguanidine, Pyridoxamine.
2. “AGE breakers”: Dimethyl-3-phenyl-thiazolium chloride.
3. Neutriceuticals: Ascorbic acid, α-tocopherol,pyridoxal
4. Caloric restriction and dietary measures.
5. Targeting RAGE

19. CONCLUSION
• AGEs form when proteins or lipids interact with
reducing sugars for an extended period of time.
• They impart maladaptive signatures in the vessel
wall.
• To understanding AGE formation and
biochemistry, cellular receptors for AGE, AGE-
induced effects on extracellular and intracellular
function is important to find effective therapies
against AGEs.