Metabolism of Fructose and Galactose

Question 1

name the GLUT transporter of fructose and the dietary sources of fructose

Answer 1

dietary fructose absorbed by GLUT-5

• sucrose (digested by intestinal sucrase)
• fruits and honey
• HFCS (55% fructose/45% glucose)
• sorbitol; can form fructose by sorbitol dehydrogenase

Question 2

describe benign fructosuria (essential fructosuria)

Answer 2

• deficiency of fructokinase in liver
• on ingesting surcorse, fructose is not metaboilzed and is excreted in urine in these children
  
  • Clinitest with urine reveal the presence of a reducing sugar
  • no toxic metabolites of fructose accumulate in liver; asymptomatic

Question 3

describe hereditary fructose intolerance

Answer 3

• deficiency of aldolase B in the liver
• ingestion of sucrose or fructose results in trapping of fructose 1-phosphate in hepatocytes
  
  • trapping of Pi results in ATP deficiency -> inhibits gluconeogenesis -> hypoglycemia
  • trapping of Pi also inhibits glycogenolysis -> hypoglycemia
• inhibition of gluconeogenesis + glycogenolysis = hypoglycemia (drowsy, apathetic)
  
  • hypoglycemia occurs following consumption of sucrose/fructose, NOT in fasting state

Question 4

patients with hereditary fructose intolerance who continue to ingest fructose/sucrose/sorbitol in their diet can manifest with features of ______ and manifest with _____

Answer 4

patients with hereditary fructose intolerance who continue to ingest fructose/sucrose/sorbitol in their diet can manifest with features of hepatocellular failure and manifest with jaundice

Question 5

describe the location of fructose in patients with hereditary fructose intolerance

Answer 5

• urine analysis detects the presence of a reducing sugar (fructose)
• children with fructose intolerance DO NOT have cataracts

Question 6

describe the synthesis of fructose from glucose (polyol pathway)

Answer 6

Question 7

contrast age of diagnosis of fructose intolerance with galactose intolerance

Answer 7

• fructose intolerance usually around 6-8 months since there is no fructose in breast milk; usually seen when fruits are introduced into diet
• galactose intolerance is seen immediately since galactose is found in breast milk

Question 8

dietary galactose is absorbed into the intestinal mucosal cell by _____

Answer 8

dietary galactose is absorbed into the intestinal mucosal cell by SGLT-1

Question 9

describe galactose metabolism

Answer 9

Question 10

what enzyme is deficient in classical galactosemia and how does it affect organs

Answer 10

• galactose 1-phosphate uridyl transferase (GALT) which is autosomal recessive
• accumulation of galactose 1-phosphate in the liver traps phosphate and inhibits gluconeogenesis + glycogenolysis
  
  • jaundice and hepatomegaly
• galactose in the lens results in formation of galactitol (by actvity of aldose reductase); osmotically active and increases water content of the lens
• galactose 1-P accumulates in the brain resulting in neurological damage

Question 11

describe non-classical galactosemia

Answer 11

• deficiency of galactokinase
• accumulation of galactitol results in early cataract formation
• urine is positive for reducing sugar

Question 12

describe lactose synthesis

Answer 12

• lactose synthesis takes place in the mammary gland during lactation
• alpha-lactalbumin (protein B) synthesis is stimulated by prolactin (secreted during lactation)
  
  • alpha-lactalbumin (protein B) is found only in lactating mammary gland

Question 13

summarize the enzyme deficiencies in the fructose/galactose metabolism disorders

Answer 13