Galactose and Fructose Metabolism

Question 1

Where do galactose and fructose come from?

Answer 1

• lactose –> glucose + galactose
• sucrose –> glucose + fructose
• (maltose –> glucose x2)

Question 2

Which organs does galactose mainly enter? What about fructose?

Answer 2

• galactose: the liver and the brain

- fructose: the liver and the kidney

Question 3

Which enzyme converts galactose into ____________?

Answer 3

• galactokinase converts galactose into galactose-1-phosphate

Question 4

Which enzyme converts galactose-1-phosphate into ___________? What happens to this product?

Answer 4

• galactose-1-phosphate uridyltransferase converts galactose-1-phosphate into glucose-1-phosphate, which can enter either the pathway for glycogen or be converted to glucose-6-phosphate (and enter glycolysis or gluconeogenesis from here)

Question 5

What is galactosemia? When does it occur?

Answer 5

• elevated levels of galactose in the blood; results from a deficiency in either galactokinase or galactose-1-phosphate uridyltransferase

Question 6

Compare a deficiency in galactokinase to a deficiency in galactose-1-phosphate uridyltransferase.

Answer 6

• galactokinase: results in mild galactosemia; cataracts
• galactose-1-phosphate uridyltransferase: results in severe galactosemia; cataracts, vomiting, diarrhea, lethargy, liver damage, hypobilirubinemia, mental retardation
• (remember, galactose is mainly taken up by the liver and the brain, so the symptoms reflect these organs)

Question 7

Why is galactosemia much more severe in a deficiency of galactose-1-phosphate uridyltrasnferase than in a deficiency of galactokinase?

Answer 7

• galactokinase phosphorylates galactose, keeping it in the cell; so if this enzyme is deficient, galactose can leave the cell before accumulating to toxic levels
• in galactose-1-phosphate uridyltrasnferase deficiency, galactose is phosphorylated and stuck in the cell and can’t be metabolized, so it accumulates

Question 8

Explain the pathogenesis of cataracts in galactosemia.

Answer 8

• when galactose accumulates in the blood, it eventually enters the lens of the eyes, which contain an enzyme (aldose reductase) that converts galactose to an alcohol (galactatol); alcohols are highly osmotic and draw in fluid, resulting in swelling and cataracts
• (this is the same mechanism that causes blindness in diabetics! except with glucose being converted into glucitol/sorbitol)

Question 9

Which enzyme converts fructose into ___________?

Answer 9

• fructokinase converts fructose into fructose-1-phosphate

Question 10

Which enzyme converts fructose-1-phosphate into ____________?

Answer 10

• aldolase B converts fructose-1-phosphate into glyceraldehyde and dihydroxyacteone-P, both of which can be converted into glyceraldehyde-3-P (to partake in glycolysis or gluconeogenesis)

Question 11

Aldolase A vs. Aldolase B

Answer 11

• aldolase A converts fructose-1,6-BP into G3P and DHAP

- aldolase B converts fructose-1-P into glyceraldehyde and DHAP

Question 12

Fructokinase deficiency vs. aldolase B deficiency

Answer 12

• fructokinase deficiency: essential fructosuria (benign)
• aldolase B deficiency: hereditary fructose intolerance (lethargy, vomiting, liver damage, hyperbilirubinemia, hypoglycemia, hyperuricemia, Fanconi syndrome)
• remember, fructose mainly enters the liver and the kidneys, which explains the symptoms
• (again the 2nd is worst than the 1st for the same reason explained in galactosemia)