Pentose Phosphate Pathway

Question 1

What is the purpose of the Pentose Phosphate Pathway?

Answer 1

The pentose phosphate pathway oxidizes glucose to make NADPH and other carbohydrates for biosynthesis.

The major route for reduction of NADP to NADPH is the reaction of glucose‐6‐phosphate through two successive reactions.

In the first, carbon 1 of glucose is oxidized from an aldol to an ester form (actually, an internal ester, called a lactone) by glucose‐6‐phosphate dehydrogenase.

In the second reaction, the same carbon is further oxidized to CO ₂ and released, leaving behind a 5‐carbon sugar, in a reaction catalyzed by 6‐phosphogluconolactone‐dehydrogenase.

Both reactions reduce NADP to NADPH. The 5‐carbon residue is ribulose‐5‐phosphate

Question 2

What else can the PPP be used for?

Answer 2

The PPP can also be used to produce glyceraldehyde-3-phosphate which can then be fed into the TCA and ETC cycles allowing for the harvest of energy.

The PPP also produces Ribose-5-phosphate which is an important part of nucleic acids.

Question 3

Where are the enzymes used for the PPP found?

Answer 3

The enzymes reasonable for catalyzing the steps of the PPP are found most abundantly in the liver (the major site of gluconeogenesis) more specifically in the cytosol.

The cytosol is where fatty acid synthesis takes place which is a NADPH dependent process.

Question 4

What does the oxidation phase of the PPP consist of?

Answer 4

• The beginning molecule for the PPP is glucose-6-P which is the second intermediate metabolite in glycolysis. Glucose-6-P is oxidized in the presence of glucose-6-P dehydrogenase and NADP⁺. This step is irreversible and is highly regulated. NADPH and fatty acyl-CoA are strong negative inhibitors to this enzyme. The purpose of this is to decrease production of NADPH when concentrations are high or the synthesis of fatty acids is no longer necessary.
• The metabolic product of this step is gluconolactone which is hydrolytrically unstable. Gluconolactonase causes gluconolactone to undergo a ring opening hydrolysis. The product of this reaction is the more stable sugar acid, 6-phospho-D-gluconate.
• 6-phospho-D-gluconate is oxidized by NADP⁺ in the presence of 6-phosphogluconate dehydrogenase which yields ribulose-5-phosphate.
• The oxidation phase of the PPP is solely responsible for the production of the NADPH to be used in anabolic processes.

Question 5

What is the isomerization phase of the PPP?

Answer 5

• Ribulose-5-phosphate can then be isomerized by phosphopentose isomerase to produce ribose-5-phosphate. Ribose-5-phosphate is one of the main building blocks of nucleic acids and the PPP is the primary source of production of ribose-5-phosphate.
• If production of ribose-5-phosphate exceeds the needs of required ribose-5-phosphate in the organism, then phosphopentose epimerase catalyzes a chiralty rearrangement about the center carbon creating xylulose-5-phosphate.
• The products of these two reactions can then be rearranged to produce many different length carbon chains. These different length carbon chains have a variety of metabolic fates.

Question 6

What is the rearrangement phase of the PPP?

Answer 6

• There are two main classes of enzymes responsible for the rearrangement and synthesis of the different length carbon chain molecules. These are transketolase and transaldolase.
• Transketolase is responsible for the cleaving of a two carbon unit from xylulose-5-P and adding that two carbon unit to ribose-5-P thus resulting in glyceraldehyde-3-P and sedoheptulose-7-P.
• Transketolase is also responsible for the cleaving of a two carbon unit from xylulose-5-P and adding that two carbon unit to erythrose-4-P resulting in glyceraldehyde-3-P and fructose-6-P.
• Transaldolase is responsible for cleaving the three carbon unit from sedoheptulose-7-P and adding that three carbon unit to glyceraldehyde-3-P thus resulting in erythrose-4-P and fructose-6-P.
• The end results of the rearrangement phase is a variety of different length sugars which can be fed into many other metabolic processes. For example, fructose-6-P is a key intermediate of glycolysis as well as glyceraldehyde-3-P.

Question 7

Picture of the oxidative stages of the PPP.

Answer 7

Question 8

Picture of the non-oxidative stages of the PPP.

Answer 8