Pentose phosphate pathway Flashcards
What is the pentose phosphate pathway ?
- it is a pathway used by all organisms
- it generates NADPH for anabolic metabolism
- it yields 5C sugars for nucleotide biosynthesis
- excess 5C sugars are converted into glycolytic intermediates
Where does the pentose phosphate pathway take place ?
it is located in the cytosol
What are the 2 phases of the pentose phosphate pathway ?
phase 1 : oxidative generation of NADPH
phase 2 : interconversion of sugars
Describe phase 1 of the pentose phosphate pathway
1) glucose 6 phosphate is oxidised by glucose 6 phosphate dehydrogenase and NADP+ is reduced to NADPH
2) the product is hydrolysed by a specific lactonase
3) ribulose 5 phosphate is produced by oxidative decarboxylation with NADP+ as the electron acceptor
4) ribulose 5 phosphate is isomerised to ribose 5 phosphate
Describe the role of glucose 6 phosphate dehydrogenase
- it has a key role in protection against reactive oxygen species
- the NADPH which is generated helps to maintain glutathione in a reduced state
- reduced glutathione is required to combat oxidative stress
What is glutathione ?
- a small molecule ~ 3 amino acids
- it can be in an oxidised or reduced state
Describe glucose 6 phosphate dehydrogenase deficiency
- glucose 6 phosphate dehydrogenase deficiency is the most common enzymopathy
- it affects 10% of the worlds population
- it is an inheritable X linked recessive disorder
What are the effects of glucose 6 phosphate dehydrogenase deficiency ?
- the primary effect is on red blood cells
- cells become damaged and lyse
- urine turns black and the haemoglobin content drops sharply
- may cause death
What are the advantages of glucose 6 phosphate dehydrogenase deficiency ?
- gives protection against plasmodium falciparum malaria
- the parasite is required for reduced glutathione
Describe the metabolic fate of ribulose 5 phosphate
- ribulose 5 phosphate can be epimerised into xylulose 5 phosphate by the enzyme phosphopentose epimerase
- the amount of ribose 5 phosphate and xylulose 5 phosphate production is dependent on the biosynthetic requirement
How are the pentose phosphate pathway and glycolysis linked ?
- the 5C sugars are converted into glycolytic intermediates by 3 fully reversible enzyme reactions
- transketolase and transaldolase enzymes are used
- the net result is the production of 2 6C sugars and 1 3C sugar from 3 5C sugars
Describe the 1st reaction that converts 5C sugars into glycolytic intermediates
- xylulose 5 phosphate is converted to glyceraldehyde 3 phosphate
- ribose 5 phosphate is converted to sedoheptulose 7 phosphate
- a transketolase enzyme is used
Describe the 2nd reaction that converts 5C sugars into glycolytic intermediates
- glyceraldehyde 3 phosphate is converted to fructose 6 phosphate
- sedoheptulose 7 phosphate is converted to erythrose 4 phosphate
- a transaldolase enzyme is used
Describe the 3rd reaction that converts 5C sugars into glycolytic intermediates
- erythrose 4 phosphate is converted fructose 6 phosphate
- xylulose 5 phosphate is converted to glyceraldehyde 3 phosphate
- a transketolase enzyme is used
Describe the effects if there is a mutation or deficiency of the transketolase enzyme
- causes a disorder known as Wernicke - Korsakoff syndrome
- symptoms include memory loss and partial paralysis
- alcoholics are more likely to manifest it