Module 4 - Pentose Phosphate Pathway Flashcards
Glucose-6-Phosphate Dehydrogenase
This enzyme catalyzes the first committed step in the PPP and is rate-limiting
NADPH
A major product of the PPP and the major currency of reducing equivalents in the cell that are used in a variety of biosynthetic reactions.
Pentose Phosphate Pathway
A pathway for glucose degradation that yields ribose 5-phosphate and NADPH.
Transaldolase and Transketolase
Two enzymes that catalyze reversible reactions in the non-oxidative phase of the PPP that interconvert 3-, 4-, 5-, 6-, and 7-carbon sugars.
What is the major role of PPP?
to produce NADPH, the major currency for reducing equivalents in the cell, and ribose-5-P, which is the sugar component of nucleotides
What is the starting point for PPP?
glucose-6-P is the starting point for this pathway, and is also an intermediate of glycolysis, these pathways are interconnected
Production of NADPH
plants produce NADPH through photosynthesis,
non-photosynthetic organisms generate NADPH through the PPP.
Where is the PPP active in animals?
where the synthesis of biomolecules occurs at high rates
What are the two phases of this pathway?
In the first part, the oxidative phase, glucose-6-P is oxidized and in the process, NADP+ gets reduced to NADPH.
In the second phase, the non-oxidative phase, ribulose-5-P is converted to ribose-5-P which is the second major product of this pathway.
How is the PPP connected to Glycolysis?
the second phase of the pathway is also where the interconversion of 3-, 4-, 5-, 6-, and 7-carbon sugars takes place.
These interconversions provide a way for the excess 5-carbon sugars to be converted to intermediates of glycolysis.
It is a way to divert the excess ribose-5-P to glycolysis where it can be metabolized into useful components and/or to produce ATP
Phase 1 - Oxidative Phase
The pathway starts with glucose-6-P, which is an intermediate of both glycolysis and gluconeogenesis
for every glucose-6-P molecule that enters the pathway, two NADPH are produced.
Ribulose-5-P, a 5-carbon sugar, is the end-product of this phase
Phase 2: Non-Oxidative Phase
The major goal of this phase is to convert ribulose-5-P to ribose-5-P, which is catalyzed by an isomerase
What are the glycolytic intermediates of Ribose-5-P?
These reversible conversions are catalyzed by two enzymes, transketolase and transaldolase
the products of these reactions include glyceraldehyde-3-P and fructose-6-P, both of which are glycolytic intermediates
How is the PPP regulated?
The most important point to remember about the regulation of the PPP is that it is the cytosolic concentration of NADP+ which plays the biggest role.
What is the rate-limiting step?
the very first step of this pathway is catalyzed by glucose-6-P dehydrogenase.
This pathway is the rate-limiting step i.e., the slowest step
How is glucose-6-P metabolized?
glucose-6-P can be metabolized by both glycolysis and the PPP, since both pathways take place in the cytosol
the fate of glucose-6-P is highly dependent on the cell’s need for NADPH.
If the need is low, then more will be metabolized through glycolysis.
If there is high demand for NADPH, more will be metabolized through the PPP.
Coordinated regulation between glycolysis and PPP
the decision as to whether glucose-6-P will be metabolized by glycolysis or the PPP is also guided by the need of the cell for ribose-5-P and ATP which are important products of the PPP and glycolysis
What happens when the need for ribose-5-P is greater than the need for NADPH?
arises in cells that are rapidly dividing and have to synthesize a lot of DNA
most of the glucose-6-P is metabolized through glycolysis to fructose-6-P and glyceraldehyde-3-P
These two molecules can then be used by the non-oxidative portion of the PPP, using the reversible reactions catalyzed by transketolase and transaldolase, to produce ribose-5-P
What happens when the need for NADPH and ribose-5-P are about the same?
glucose-6-P is metabolized through the oxidative portion of the PPP where NADPH is produced.
The ribulose-5-P that is produced is converted to ribose-5-P.
This results in the replenishment of both NADPH and ribose-5-P.
What happens when the need for NADPH is greater than that for ribose-5-P?
occurs in liver,
there are three sets of reactions that in the end result in the complete oxidation of glucose-6-P to CO2 with the formation of NADPH.
First, glucose-6-P is converted to ribulose-5-P by the oxidative portion of the PPP which results in NADPH production.
The ribulose-5-P that is produced is easily and rapidly converted to ribose-5-P, which is then converted to fructose-6-P and glyceraldehyde-3-P by the non-oxidative reactions of the PPP.
These two metabolites can then be used in gluconeogenesis to produce glucose-6-P.
If one writes out the stoichiometry of all three of these reaction sets, one finds that every glucose-6-P is oxidized to 6CO2 with 12 NADPH produced.
What happens when both NADPH and ATP are required?
glucose-6-P is metabolized through the oxidative portion of the PPP which produces NADPH.
The ribulose-5-P produced is converted to fructose-6-P and glyceraldehyde-3-P by the non-oxidative portion of the PPP.
Both of these metabolites can then enter glycolysis and be metabolized to pyruvate, which produces ATP.
