Pentose Phosphate Pathway & Galactose Metabolism Flashcards
Which 2 enzymes could be absent in galactosaemia?
- Galactokinase (rare)
- Galactose-1-P uridyl transferase (more common)
What could an absence of GALACTOKINASE cause?
- Galactokinase is used to convert galactose -> galactose-1-P
- Absence causes a buildup of galactose
- Galactose is converted to GALACTITOL by the enzyme ALDOSE REDUCTASE and requires NADPH
- NADPH stores are depleted so cells are more susceptible to oxidative damage
Explain how an accumulation of galactose can lead to cataracts
- Galactose converted to GALACTITOL by aldose reductase and NADPH
- This depletes the NADPH stores within the cell so NADPH is not available to recycle the antioxidant glutathione (cells more susceptible to oxidative damage)
- NADPH is unable to reduce the formation of inappropriate S-S bonds in lens of eye, causing cataracts
How might the accumulation of galactose and galactitol in the lens of the eye cause blindness?
Accumulation may lead to increase in intra-ocular pressure (GLAUCOMA) which if untreated can cause blindness
Explain why an absence of galactose-1-P uridyl transferase may be more serious than an absence of galactokinase
- Absence of transferase enzyme leads to accumulation of both galactose AND galactose-1-P
- Galactose-1-P can cause damage to liver, kidney and brain
Describe how fructose is obtained from the diet
Dietary sucrose is broken down in gut by SUCRASE to glucose and fructose
Where is fructose metabolised?
LIVER
How does fructose enter metabolism?
Converted to GLYCERALDEHYDE-3-PHOSPHATE which is an intermediate of glycolysis
What are the major functions of the pentose phosphate pathway?
- Produce NADPH which is used for the recycling of glutathione (protect against oxidative stress) and in synthesis of lipids
- Production of 5C ribose sugars which are used in the synthesis of DNA and RNA nucleotides
How does the pentose phosphate pathway differ from glycolysis?
Both pathways are oxidative but in pentose phosphate pathway there is:
- No production of ATP
- CO2 is produced
Describe and outline the mechanisms that occur in phase 1 of the pentose phosphate pathway
- Glucose-6-P is converted to 5C sugar through OXIDATIVE DECARBOXYLATION (C is lost in the form of CO2)
- Catalysed by the enzyme glucose-6-P dehydrogenase (G6PD)
- Glucose-6-P + 2NADP+ —> 5C compound + 2NADPH + CO2 + 2H+
Describe how the 5C compounds produced in the pentose phosphate pathway can enter glycolysis
3 5C sugar phosphate —> 2 fructose-6-phosphate + glyceraldehyde-6-phosphate
How is the pentose phosphate pathway regulated?
- Glucose-6-phosphate dehydrogenase is the key regulatory enzyme
- Activity is controlled by the NADP+/NADPH ratio
- NADP+ activates, whereas NADPH inhibits
Explain how G6PD deficiency is caused and how it can be linked to haemolytic anaemia
- X linked gene defect
- Point mutation in gene coding for G6PD resulting in reduced activity of enzyme and therefore LOW LEVELS OF NADPH
- Cells are at increased risk of oxidative damage
- S-S cross links can occur in Haemoglobin, forming aggregates know as Heinz bodies
- a Premature destruction of RBCs (haemolysis) can cause anaemia
Explain how pyruvate is metabolised and why the reaction is irreversible
- Pyruvate is converted to Acetyl CoA using PYRUVATE DEHYDROGENASE
- Involves loss of C as CO2 which is IRREVERSIBLE
- Acetyl CoA cannot be converted to pyruvate (and therefore cannot be converted to glucose via gluconeogenesis)
