GALACTOSE AND FRUCTOSE(2).pptx

explains on fructose and galactose
metabolism

1. GALACTOSE METABOLISM V.ARUNA- DEPARTMENT OF BIOCHEMISTRY

2. Lactose , presen t in mil k & mil k pro d ucts. 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. G a lactosemia

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 Thi s is the rat e limiting enzyme.

6. Galactose 1-phosphate reacts with UDP- glucose to f orm UD P - galactose & gl u cos e 1 - phosphate, in the presence of the enzyme Galactose 1-phosphate uridyl transferase

7. UDP-galactose is an active donor of galactose. UDP-galactose is essential for the formation of compounds like lactose, glycosaminoglycans, glyc oprot e ins, cerebrosi d e s & gl y colipi d s. Step: 3 Epimerase reaction: UDP-galactose can be converted to UDP- glucose by UDP hexose 4-epimerase

8. 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+

9. Step: 4 Alternate pathway: The galactose 1-phosphate pyrophosphorylase in liver becomes active only afte r 4 o r 5 year s of life The enzyme will produce UDP-galactose directly which can be epimerized to UDP- glucose.

10. Galactose 1-phosphate Glucose 1-phosphate Glycolysis G l uc o se Ga lactit o l UDP-Glucose UDP-Galactose Lactose GAGS Glycolipids Glycop r oteins NA D P A DP Galactose ATP Gal a c t o k in a se Gala-1-Pho-Uridyl t ran s fer a s e E p i m e r a s e Muta se Synthase Glucose 6-phosphate Galactose Metabolism

11. 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

12. Salient features Due to the block in this enzyme, galactose 1- phosphate will accumulate in liver. Thi s will inhibit galactokinase a s well a s glycogen phosphorylase It results in hypoglycemia. Galactose cannot be converted to glucose Increased galactose level increases insulin secretion, which lowers blood glucose level .

13. Galactose metabolism is impaired leading to increased galactose levels in circulation ( galactos e mi a ) & ur i n e ( galactosuri a ) Bilirubin uptake is less & bilirubin conjugation is reduced. Unconjugated bilirubin level is increased.

14. There is enlargement of liver, jaundice & severe mental retardation – due to accu m ilati o n of gala ctos e & gala ctos e 1 - phosphate.

15. 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 .

16. 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: Remo v a l of galactose & l a ctos e from the diet .

17. Fructose metabolism Fructose is p resen t in fru i t ju i ce s & 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 .

18. Fructose is e asily met a b o liz e d & 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.

19. 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 F r u ct o se Fr u ct o s e - 6 - p Glucose-6-p E. M path w a y A TP ADP Hexokinase Isomerase

20. 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 .

21. 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.

22. Fructose entering glycolysis

23. Fructose S o rbi tol Fru-1-P Glycerol Gluco s e Fru-6-P DHAP NA D P NADPH+H + Reductase N A D+ NADH+H + DH Gluco s e 6 - P DHAP Glyceraldehyde 3-P PF K F - 1, 6 b i s - P Fru 1,6-BisP H ex o k inas e ATP F r ucto k inase A TP Aldolase B Triokinase A TP Glycerol kinase Glycerol 3-P ATP DH Gl y cogen Glyceraldehyde NADH+H + NAD

24. 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+

25. Sorbitol pathway

26. 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.

27. This results 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.

28. 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.

29. 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 Urin e gives positive benedicts & seliwa noff ’s test

30. 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

31. Vomiting, loss of appetite, hepatomegaly & jaundice. If liver damage progresses, death will occur. Fructose is excreted in urine. Restriction of dietary fructose.

32. One or more hydroxyl groups of the monosaccharides are replaced by amino groups G luco E.g.D -g samine , D-galactosamine, mannoseamine, sialic acid. They are present as constituents of GAG’s, gl y colipi d s & glycopr o tein s . Also found in some oligosaccharides & antibiotics.

33. The amino groups of amino sugars are sometimes acetylated e.g.N-acetyl D-glucosamine Fructose 6-phosphate is major precursor for gl u cosamin e , N - ace t ylga lactosam i n e & NANA. N-Acetyl neuramic acid (NAN) is derivative of N- Acetyl m a n nose & pyruv i c acid. 2 0% of glucose is utilized for the synthesis of amino sugars, which mostly occurs in the connective tissues.

34. G luc o s e Glu-6-P Fr u - 6 - P Glucose am i n e - 6 - P Glucose Am i ne - 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 - N A NA Sialic acid Gangliosides Gly c oprot e ins GAGS Glucosamine PEP Epimerase Epimerase UTP C TP UTP

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