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Gandham.Rajeev
Email:gandhamrajeev33@gmail.com
• Lactose, present in milk & milk products.
• Principal dietary source of galactose.
• Lactase ( β-galactosidase ) of inte...
• Galactose is metabolised almost exclusively
by the liver and therefore galactose
tolerance test is done to assess the fu...
• Step: 1
• Galactokinase reaction:
• Galactose is first phosphorylated by
galactokinase to galactose -1- phosphate
• Step...
• Galactose 1-phosphate reacts with UDP-
glucose to form UDP-galactose & glucose 1-
phosphate, in the presence of the enzy...
• UDP-galactose is an active donor of galactose.
• UDP-galactose is essential for the formation of
compounds like lactose,...
• Galactose is channeled to the metabolism of
glucose.
• Galactose is not an essential nutrient since
UDP-glucose can be c...
• Step: 4
• Alternate pathway:
• The galactose 1-phosphate
pyrophosphorylase in liver becomes active
only after 4 or 5 yea...
Galactose
Galactose 1-phosphate
Glucose 1-phosphate
Glucose 6-phosphate
Glycolysis Glucose
Galactitol
UDP-Glucose
UDP-Gala...
Disorders of galactose metabolism
• Classical galactosemia:
• Due to deficiency of enzyme galactose 1-
phosphate uridyltra...
Salient features
• Due to the block in this enzyme, galactose 1-
phosphate will accumulate in liver.
• This will inhibit g...
• Galactose metabolism is impaired leading to
increased galactose levels in circulation
(galactosemia) & urine (galactosur...
• There is enlargement of liver, jaundice &
severe mental retardation – due to
accumilation of galactose & galactose 1-
ph...
Galactosemia
Development of cataracts
• Causes:
• Excess of galactose in lens is reduced to galactitol
(dulcitol) by the enzyme aldose ...
Galactokinase deficiency
• The defect in the enzyme galactokinase.
• Results in galactosemia & galactosuria
• Dulcitol or ...
Fructose metabolism
• Fructose is present in fruit juices & honey.
• Chief dietary source is sucrose.
• Sucrose is hydroly...
• Fructose is easily metabolized & a good
source of energy
• Seminal fluid is rich in fructose &
spermatozoa utilizes fruc...
Fructose metabolism
• Fructose is phosphorylated to form fructose 6-
phospate, catalyzed by the enzyme
hexokinase
• Affini...
• Fructose is mostly phosphorylated by
fructokinase to fructose-1-phosphate
• Fructokinase is present in liver, kidney,
mu...
• Fructose-1-phosphate is cleaved to
glyceraldehyde & dihydroxy acetone
phosphate (DHAP) by aldolase B
• Glyceraldehyde is...
Fructose entering glycolysis
Fructose
Sorbitol
Fru-1-P
Glyceraldehyde
Glycerol
Glucose
Fru-6-P
DHAP
NADP NADPH+H+
Reductase
NAD+
NADH+H+
DH
Glucose 6-P...
• It involves the conversion of glucose to
fructose via sorbitol
• Sorbitol pathway is higher in uncontrolled
diabetes
• T...
Sorbitol pathway
• In uncontrolled diabetes, large amounts of
glucose enter the cells which are not
dependent on insulin
• The cells with i...
• This results in a rapid & efficient conversion of
glucose to sorbitol
• The enzyme Sorbitol Dehydrogenase is either
low ...
• Sorbitol-due to its hydrophilic nature-causes
osmotic effects leading to swelling of the cells.
• Pathological changes a...
• Essential fructosuria:
• Deficiency of the enzyme hepatic fructokinase.
• Fructose is not converted to fructose 1-
phosp...
• An autosomal recessive inborn error.
• Due to defect in the enzyme aldolase-B.
• Fructose 1-phosphate, cannot be metabol...
• Vomiting, loss of appetite, hepatomegaly &
jaundice.
• If liver damage progresses, death will occur.
• Fructose is excre...
• One or more hydroxyl groups of the
monosaccharides are replaced by amino groups
• E.g.D-glucosamine, D-galactosamine,
ma...
• The amino groups of amino sugars are
sometimes acetylated e.g.N-acetyl D-glucosamine
• Fructose 6-phosphate is major pre...
Glucose
Glu-6-P Fru-6-P Glucose
amine-6-P
Glucose
Amine-1-P
UDP-Glucose
Amine
N-Acetyl
Glucoseamine-6P
N-Acetyl
Glucoseami...
References
• Textbook of Biochemistry-U Satyanarayana
• Textbook of Biochemistry-DM Vasudevan
Thank you
METABOLISM OF GALACTOSE, FRUCTOSE & AMINO SUGARS
METABOLISM OF GALACTOSE, FRUCTOSE & AMINO SUGARS
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METABOLISM OF GALACTOSE, FRUCTOSE & AMINO SUGARS

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METABOLISM OF GALACTOSE, FRUCTOSE & AMINO SUGARS

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METABOLISM OF GALACTOSE, FRUCTOSE & AMINO SUGARS

  1. 1. Gandham.Rajeev Email:gandhamrajeev33@gmail.com
  2. 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. 3. • 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
  4. 4. • 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.
  5. 5. • 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
  6. 6. • 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
  7. 7. • 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+ • Galactose is not essential in diet
  8. 8. • Step: 4 • Alternate pathway: • The galactose 1-phosphate pyrophosphorylase in liver becomes active only after 4 or 5 years of life • The enzyme will produce UDP-galactose directly which can be epimerized to UDP- glucose.
  9. 9. Galactose Galactose 1-phosphate Glucose 1-phosphate Glucose 6-phosphate Glycolysis Glucose Galactitol UDP-Glucose UDP-Galactose Lactose GAGS Glycolipids Glycoproteins NADP ATP ADP Galactokinase Gala-1-Pho-Uridyl transferase E p i m e r a s e Mutase Synthase Galactose Metabolism
  10. 10. 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
  11. 11. 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.
  12. 12. • 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.
  13. 13. • There is enlargement of liver, jaundice & severe mental retardation – due to accumilation of galactose & galactose 1- phosphate.
  14. 14. Galactosemia
  15. 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. 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: • Removal of galactose & lactose from the diet.
  17. 17. 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.
  18. 18. • 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.
  19. 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 Fructose Fructose -6-p Glucose-6-p E.M pathway ATP ADP Hexokinase Isomerase
  20. 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. 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. 22. Fructose entering glycolysis
  23. 23. Fructose Sorbitol Fru-1-P Glyceraldehyde Glycerol Glucose Fru-6-P DHAP NADP NADPH+H+ Reductase NAD+ NADH+H+ DH Glucose 6-P Fru 1,6-BisP Glycerol 3-P DHAP Glyceraldehyde 3-P PFK F-1,6 bis-P Hexokinase ATP FructokinaseATP Aldolase B Triokinase ATP Glycerol kinase ATP DH Glycogen NADH+H+ NAD
  24. 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. 25. Sorbitol pathway
  26. 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. 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. 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. 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 • Urine gives positive benedicts & seliwanoff’s test
  30. 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. 31. • Vomiting, loss of appetite, hepatomegaly & jaundice. • If liver damage progresses, death will occur. • Fructose is excreted in urine. • Restriction of dietary fructose.
  32. 32. • One or more hydroxyl groups of the monosaccharides are replaced by amino groups • E.g.D-glucosamine, D-galactosamine, mannoseamine, sialic acid. • They are present as constituents of GAG’s, glycolipids & glycoproteins. • Also found in some oligosaccharides & antibiotics.
  33. 33. • 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 & pyruvic acid. • 20% of glucose is utilized for the synthesis of amino sugars, which mostly occurs in the connective tissues.
  34. 34. 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- acetylgalactosamineCMP-NANA Sialic acid Gangliosides Glycoproteins GAGS Glucosamine PEP Epimerase Epimerase UTP CTP UTP
  35. 35. References • Textbook of Biochemistry-U Satyanarayana • Textbook of Biochemistry-DM Vasudevan
  36. 36. Thank you

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