Pentose Phosphate Pathway & Galactose Metabolism Flashcards Preview

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Flashcards in Pentose Phosphate Pathway & Galactose Metabolism Deck (17)
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1
Q

Which 2 enzymes could be absent in galactosaemia?

A
  • Galactokinase (rare)

- Galactose-1-P uridyl transferase (more common)

2
Q

What could an absence of GALACTOKINASE cause?

A
  • 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
3
Q

Explain how an accumulation of galactose can lead to cataracts

A
  • 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
4
Q

How might the accumulation of galactose and galactitol in the lens of the eye cause blindness?

A

Accumulation may lead to increase in intra-ocular pressure (GLAUCOMA) which if untreated can cause blindness

5
Q

Explain why an absence of galactose-1-P uridyl transferase may be more serious than an absence of galactokinase

A
  • 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
6
Q

Describe how fructose is obtained from the diet

A

Dietary sucrose is broken down in gut by SUCRASE to glucose and fructose

7
Q

Where is fructose metabolised?

A

LIVER

8
Q

How does fructose enter metabolism?

A

Converted to GLYCERALDEHYDE-3-PHOSPHATE which is an intermediate of glycolysis

9
Q

What are the major functions of the pentose phosphate pathway?

A
  • 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
10
Q

How does the pentose phosphate pathway differ from glycolysis?

A

Both pathways are oxidative but in pentose phosphate pathway there is:

  • No production of ATP
  • CO2 is produced
11
Q

Describe and outline the mechanisms that occur in phase 1 of the pentose phosphate pathway

A
  • 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+
12
Q

Describe how the 5C compounds produced in the pentose phosphate pathway can enter glycolysis

A

3 5C sugar phosphate —> 2 fructose-6-phosphate + glyceraldehyde-6-phosphate

13
Q

How is the pentose phosphate pathway regulated?

A
  • Glucose-6-phosphate dehydrogenase is the key regulatory enzyme
  • Activity is controlled by the NADP+/NADPH ratio
  • NADP+ activates, whereas NADPH inhibits
14
Q

Explain how G6PD deficiency is caused and how it can be linked to haemolytic anaemia

A
  • 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
15
Q

Explain how pyruvate is metabolised and why the reaction is irreversible

A
  • 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)
16
Q

How may the metabolism of pyruvate be inhibited?

A
  • Acetyl CoA (produced for β-oxidation of fatty acids) can inhibit pyruvate dehydrogenase ALLOSTERICALLY
  • PDH is also inhibited by high energy signals such as ATP and NADH and activated by low energy signals such as ADP and NAD+
  • Activated by INSULIN as it promotes its dephosphorylation
17
Q

How is galactose obtained from the diet?

A

Dietary lactose is broken down in small intestine by LACTASE to form glucose and galactose