MBIO 3032 - Slide deck 7 (part 9: pentose phosphate pathway)

Pentose phosphate pathway

While some organisms do use the PP pathway for catabolic purposes, it is also important for biosynthetic intermediates, as it is used for the synthesis of ribose/pentose.

Two phases of the PP pathway

1.) It has an oxidation state, which involves the oxidation of glucose 6-phosphate into ribulose 5-phosphate

2.) Then it has the nonoxidative state, which involves converting ribulose 5-phosphate back into glucose 6-phosphate

Importance of the oxidative phase in the PP pathway

The oxidative phase is important for organisms that grow on hexoses, since it is the common way of converting hexoses to pentoses for biosynthesis, such that the pentoses is then used to make nucleotides, coenzymes, DNA, RNA, etc.

Step 1 of the PP pathway (oxidative)

Glucose —> glucose 6-phosphate, using hexose kinase, by hydrolyzing ATP

Step 2 of the PP pathway (oxidative)

Glucose 6-phosphate —> 6-phosphogluconolactone, using glucose 6-phosphate dehydrogenase, producing an NADPH in the process

Which step(s) of hexose modification are common to EMB, ED and PPP?, Which step(s) are common to ED and PPP only?

1.) Common to all three: glucose —> glucose 6-phosphate (hexose kinase)

2.) Common to EDP and PPP only: Glucose 6-phosphate —> 6-phosphogluconolactone (glucose 6-phosphate dehydrogenase)

AND

6-phosphogluconolactone —> 6 phosphogluconate (lactonase)

Step 3 of the PP pathway (oxidative)

6-phosphogluconolactone —> 6-phosphogluconate, using lactonase, which hydrates the molecule

Step 4 of the PP pathway (oxidative)

6-phosphogluconate —> ribulose 5-phosphate, using 6-phosphogluconate dehydrogenase, releasing an NADPH and a CO2 in the process

What step distinguishes the PP pathway from the ED pathway

The step that converts 6-phosphogluconate —> ribulose 5-phosphate

Step 5 of the PP pathway

Ribulose 5-phosphate —> Ribose 5-phosphate or xylulose 5-phosphate, using ribulose 5-phosphate 3-epimerase (for xylulose) and ribulose 5-phosphate isomerase (for ribose)

Step 6 of the PP pathway

Xylulose 5-phosphate + Ribose 5-phosphate —> G3P + Sedoheptulose 7-phosphate, using transketolase

Step 7 of the PP pathway

G3P + sedoheptulose 7-phosphate —> Erythrose 4-phosphate + Fructose 6-phosphate, using transaldolase

Step 8 of the PP pathway

Erythrose 4-phosphate + Xylulose 5-phosphate —> Fructose 6-phosphate + G3P, using transketolase

Net yield of pentose phosphate pathway, per 3 glucose

1.) 2 Fructose-6-phosphates

2.) 1 G3P

3.) 3 CO2

4.) 6 NADPH

What happens to the G3P and two fructose 6-phosphate that are made?

The G3P is funneled to the pay-off phase of glycolysis where it is converted to pyruvate and then fructose 6-phosphate is converted back into glucose 6-phosphate using phosphohexose isomerase

What is the difference between the role of Phosphohexose Isomerase in the recycling of the F-6-P through the PPP and in the EM pathway

Phosphoglucose isomerase, aka glucose 6-phosphate isomerase, converts glucose 6-phosphate to fructose 6-phosphate in the EM pathway, but converts fructose 6-phosphate to glucose 6-phosphate in the PP pathway.

Gluconobacter oxydans EDP vs. EMP

Its KEGG pentose phosphate pathway map shows it to have fructose bisphosphatase but no phosphofructokinase, indicating that it uses the ED pathway and not the EM pathway.