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GALACTOSE AND FRUCTOSE(2).pptx
- 1. GALACTOSE METABOLISM V.ARUNA- DEPARTMENT OF BIOCHEMISTRY
- 2. • Lactose, present in milk & milk products. • Principal dietary source of galactose. • Lactase ( β-galactosidase ) of intestinal mucosal cells hydrolyses lactose to galactose and glucose. • Galactose is also produced from lysosomal degradation of glycoproteins & glycolipids.
- 3. Galactosemia
- 4. • Galactose is metabolised almost exclusively by the liver and therefore galactose tolerance test is done to assess the functional capacity of the liver • UDP-galactose is the active donor of galactose during synthetic reactions
- 5. • Step: 1 • Galactokinase reaction: • Galactose is first phosphorylated by galactokinase to galactose -1- phosphate • Step: 2 • Galactose -1- phosphate uridyl transferase • This is the rate limiting enzyme.
- 6. • Galactose 1-phosphate reacts with UDP- glucose to form UDP-galactose & glucose 1- phosphate, in the presence of the enzyme Galactose 1-phosphate uridyl transferase
- 8. • UDP-galactose is an active donor of galactose. • UDP-galactose is essential for the formation of compounds like lactose, glycosaminoglycans, glycoproteins, cerebrosides & glycolipids. • Step: 3 • Epimerase reaction: • UDP-galactose can be converted to UDP- glucose by UDP hexose 4-epimerase
- 9. • Galactose is channeled to the metabolism of glucose. • Galactose is not an essential nutrient since UDP-glucose can be converted to UDP – galactose by the enzyme UDP-hexose 4- epimerase and requires NAD+
- 10. • Step: 4 • Alternate pathway: • The galactose 1-phosphate pyrophosphorylase in liver becomes active only after 4or 5years of life • The enzyme will produce UDP-galactose directly which can be epimerized to UDP- glucose.
- 11. Galactose 1-phosphate Glucose 1-phosphate Glycolysis Glucose Galactitol UDP-Glucose UDP-Galactose Lactose GAGS Glycolipids Glycoproteins NADP ADP Galactose ATP Galactokinase Gala-1-Pho-Uridyl transferase E p i m e r a s e Mutase Synthase Glucose 6-phosphate Galactose Metabolism
- 13. Disorders of galactose metabolism • Classical galactosemia: • Due to deficiency of enzyme galactose 1- phosphate uridyltransferase • Rare congenital disease in infants • Inherited as an autosomal recessive disorder
- 14. Salient features • Due to the block in this enzyme, galactose 1- phosphate will accumulate in liver. • This will inhibit galactokinase as well as glycogen phosphorylase • It results in hypoglycemia. • Galactose cannot be converted to glucose • Increased galactose level increases insulin secretion, which lowers blood glucose level.
- 15. • Galactose metabolism is impaired leading to increased galactose levels in circulation (galactosemia) & urine (galactosuria) • Bilirubin uptake is less & bilirubin conjugation is reduced. • Unconjugated bilirubin level is increased.
- 16. • There is enlargement of liver, jaundice & severe mental retardation – due to accumilation of galactose & galactose 1- phosphate.
- 19. Development of cataracts • Causes: • Excess of galactose in lens is reduced to galactitol (dulcitol) by the enzyme aldose reductase • Galactitol cannot escape from lens cells • Osmotic effect of the sugar alcohol contributes to injury of lens proteins & development of cataracts.
- 22. Galactokinase deficiency • The defect in the enzyme galactokinase. • Results in galactosemia & galactosuria • Dulcitol or galactitol is formed. • Absence of hepatic and renal complications. • Development of cataracts very rare. • Treatment: • Removal of galactose & lactose from the diet.
- 24. Fructose metabolism • Fructose is present in fruit juices & honey. • Chief dietary source is sucrose. • Sucrose is hydrolyzed in the intestine by the enzyme sucrase. • Fructose is absorbed by facilitated transport and taken by portal blood to liver. • It is mostly converted to glucose.
- 25. • Fructose is easily metabolized & a good source of energy • Seminal fluid is rich in fructose & spermatozoa utilizes fructose for energy. • In diabetics, fructose metabolism through sorbitol pathway may account for the development of cataract.
- 26. Fructose metabolism • Fructose is phosphorylated to form fructose 6- phospate, catalyzed by the enzyme hexokinase • Affinity of the enzyme hexokinase for fructose is very low Fructose Fructose -6-p Glucose-6-p E.M pathway ATP ADP Hexokinase Isomerase
- 27. • Fructose is mostly phosphorylated by fructokinase to fructose-1-phosphate • Fructokinase is present in liver, kidney, muscle and intestine. • Hexokinase can also act on fructose to produce fructose 1-phosphate.
- 28. • Fructose-1-phosphate is cleaved to glyceraldehyde & dihydroxy acetone phosphate (DHAP) by aldolase B • Glyceraldehyde is phosphorylated by triokinase to glyceraldehyde 3-phosphate, along with DHAP enters glycolysis or gluconeogenesis.
- 30. Fructose Sorbitol Fru-1-P Glycerol Glucose Fru-6-P DHAP NADP NADPH+H+ Reductase NAD+ NADH+H+ DH Glucose 6-P DHAP Glyceraldehyde 3-P PFK F-1,6bis-P Fru 1,6-BisP Hexokinase ATP Fructokinase ATP Aldolase B Triokinase ATP Glycerol kinase Glycerol 3-P ATP DH Glycogen Glyceraldehyde NADH+H+ NAD
- 32. • It involves the conversion of glucose to fructose via sorbitol • Sorbitol pathway is higher in uncontrolled diabetes • The enzyme aldose reductase reduces glucose to sorbitol in the presence of NADPH • Sorbitol is then oxidized to fructose by Sorbitol dehydrogenase and NAD+
- 33. Sorbitol pathway
- 34. • In uncontrolled diabetes, large amounts of glucose enter the cells which are not dependent on insulin • The cells with increased intracellular glucose levels in diabetes (lens, retina, nerve cells, kidney etc) possess high activity of aldose reductase and sufficient supply of NADPH.
- 35. • Thisresults in a rapid &efficient conversion of glucose to sorbitol • The enzyme Sorbitol Dehydrogenase is either low in activity or absent in these cells. • Sorbitol is not converted to fructose. • Sorbitol cannot freely pass through the cell membrane and accumulate in the cells.
- 36. • Sorbitol-due to its hydrophilic nature-causes osmotic effects leading to swelling of the cells. • Pathological changes associated with diabetes are due to accumulation of sorbitol.
- 37. • Essential fructosuria: • Deficiency of the enzyme hepatic fructokinase. • Fructose is not converted to fructose 1- phosphate. • Excretion of fructose in urine. • Treatment: Restriction of dietary fructose • Urine gives positive benedicts & seliwanoff’s test
- 38. • An autosomal recessive inborn error. • Due to defect in the enzyme aldolase-B. • Fructose 1-phosphate, cannot be metabolised. • Intracellular accumulation of fructose 1- phosphate will inhibit glycogen phosphorylase. • Leads to accumulation of glycogen in liver & associated with hypoglycemia
- 39. • Vomiting, loss of appetite, hepatomegaly & jaundice. • If liver damage progresses, death will occur. • Fructose is excreted in urine. • Restriction of dietary fructose.
- 40. • One or more hydroxyl groups of the monosaccharides are replaced by amino groups • GlucoE.g.D-gsamine, D- galactosamine, mannoseamine, sialic acid. • They are present as constituents of GAG’s, glycolipids & glycoproteins. • Also found in some oligosaccharides & antibiotics.
- 41. • The amino groups of amino sugars are sometimes acetylated e.g.N-acetyl D-glucosamine • Fructose 6-phosphate is major precursor for glucosamine, N-acetylgalactosamine & NANA. • N-Acetyl neuramic acid (NAN) is derivative of N- Acetyl mannose & pyruvicacid. • 20% of glucose is utilized for the synthesis of amino sugars, which mostly occurs in the connective tissues.
- 42. Glucose Glu-6-P Fru-6-P Glucose amine-6-P Glucose Amine-1-P UDP-Glucose Amine N-Acetyl Glucoseamine-6P N-Acetyl Glucoseamine1-P GAGS N-Acetylmannosamine-6-P N-acetyl neuramic acid -9-P UDP-N- acetylglucosamine UDP-N- acetylgalactosamine CMP-NANA Sialic acid Gangliosides Glycoproteins GAGS Glucosamine PEP Epimerase Epimerase UTP CTP UTP
- 43. Thank you