Pentose Phosphate Pathway Essay

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what is the pentose phosphate pathway for?

– This is also called the Phosphogluconate pathway or Hexose monophosphate shunt

– Ribose 5-Phosphate – Precursor in Nucleotide Biosynthesis of RNA and DNA, NAD(P)+ and CoASH

-NOT REQUIRED FOR ENERGY PRODUCTION
• Net consumer of ATP

where does it take place?
Liver, Adipose, Adrenal cortex, Mammary glands & Gonads Tissues all important in biosynthesis
what are the 2 phases?
– Oxidation and decarboxylation (of the 6-C sugar glucose-6-P)
• 2 moles NADPH
• Ribose-5-phosphate (5-C sugar)- Recycling
• Dispersal of excess C-5 carbon units
• Glycolytic intermediates eventually produced

what are the overall oxidation decarboxylation reactions in phase 1?
step 1 phase 1: glucose-6-phosphate dehydrogenase
glucose 6 phosphate dehydrogenase catalyses the oxidation of aldehyde to a carboxylic acid in ester linkage
NADP+ is the electron acceptor
step 2 phase 1: 6-phosphogluconolactonase
catalyzes hydrolysis of the ester linkage, resulting in ring opening.
Although ring opening occurs in the absence of a catalyst, the lactonase speeds up the reaction
step 3 phase 1: phosphogluconate dehydrogenase
catalyzes oxidative decarboxylaUon of 6- phosphogluconate, to yield the 5-C ketose ribulose-5-phosphate.
The OH at C3 (C2 of product) is oxidized to a ketone. This promotes loss of the carboxyl at C1 as CO2.NADP+ behaves as an oxidant, accepting H from the oxidised components

what is the committed step in the pathway, and how is it regulated?
Glucose-6-phosphate Dehydrogenase is the committed step of the Pentose Phosphate
Pathway, it is the first step of the first phase. This enzyme is regulated by availability of the substrate NADP+.As NADPH is utilised in reducing synthetic pathways, the increasing concentration of
NADP+ stimulates the Pentose Phosphate Pathway, to replenish NADPH.

phase 2 of the pathway
Many cells require NADPH for reducWve biosynthesis. However, there is less requirement for ribose-5-phosphate. So the excess Carbon must be “disposed of” in phase 2. This produces metabolites that can feed back into GLYCOLYSIS.
phase 2 step 1:
Epimerase inter-converts stereoisomers
ribulose-5-P and xylulose-5-P.
Isomerase converts the ketose ribulose-5-P to the aldose ribose-5-P.
Both reactions involve deportation to an endiolate intermediate followed by specific re-protonation to yield the product.
Both reactions are reversible.
phase 2 step 2: transketolase
catalyzes the formaWon of glyceraldehyde 3-phosphate
(GAP) and sedoheptulose 7- phosphate from two pentoses. It does this by transfering 2-C fragment from xylulose-5-P to ribose-5-P.Transketolase uses prosthetic group thiamine pyrophosphate (TPP), a derivative of vitamin B12

phase 2 step 3: transaldolase
catalyzes transfer of a 3-C dihydroxyacetone moiety, from sedoheptulose-7-phosphate to glyceraldehyde-3-phosphate.
This produces Fructose-6- phosphate for glycolysis.
phase 2 step 4: transketolase
Same as step 2 except transfers a 2-C fragment from xylulose-5-P to erythrose-4-P instead. This produces glyceraldehyde-3- phosphate and Fructose-6- phosphate for glycolysis .
summary of phase 2 of pentose phosphate pathway:
connecting the pentose phosphate pathway to glycolysis:
MODE 1: more ribose 5-phosphate needed than NADPH (e.g. rapidly dividing cells).
Glycolysis converts all g-6-p to GAP and f-6-p. Then phase 2 of pentose phosphate pathway can use these to make ribose-5 phosphate.MODE 2: needs of ribose 5-phosphate and NADPH balanced. Pentose Phosphate pathway mainly uses its oxidaWve part (phase 1) only.

MODE 3: more NADPH needed than ribose 5-phosphate (e.g. synthesis of faVy acids). All of pentose phosphate pathway used and the resultant GAP and f-6-p molecules synthesized back to g-6-p by gluconeogenesis.

MODE 4: both NADPH and ATP required. Same as Mode 3 except GAP and f-6-p go into glycolysis.

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