Pentose Phosphate Pathway

Pentose Phosphate Pathway

Other names: Phosphogluconate PathwayHexose Monophosphate Shunt

Direct oxidative pathway

The linear part of the pathway carries out oxidation and decarboxylation of the 6-C sugar (glucose-6-P), producing the 5-C sugar (ribulose-5-P) and others

Glucose-6-phosphate Dehydrogenase catalyzes oxidation at C1 of glucose-6-phosphate, to a carboxylic acid, in ester linkage (lactone)

NADP+ serves as electron acceptor

H O

O H

H

O HH

O H

CH 2O PO 32

H

H

O H H O

O H

H

O HH

O H

CH 2O PO 32

HO

23

4

5

6

1

1

6

5

4

3 2

C

HC

CH

HC

HC

CH 2O PO 32

O O

O H

HO

O H

O H

N AD PH + H +

NADP + H 2O H +

1

2

3

4

5

6

G lucose-6-phosphate D ehydrogenase

6-Phospho- glucono-lactonase

glucose-6-phosphate 6-phoshogluconolactone 6-phosphogluconate

6-Phosphogluconolactonase catalyzes hydrolysis of the ester linkage, resulting in ring opening

The product is 6-phosphogluconate

Although ring opening occurs in the absence of a catalyst, 6-Phosphogluconolactonase speeds up the reaction, decreasing the lifetime of the highly reactive and potentially toxic, 6-phosphogluconolactone

H O

O H

H

O HH

O H

CH 2O PO 32

H

H

O H H O

O H

H

O HH

O H

CH 2O PO 32

HO

23

4

5

6

1

1

6

5

4

3 2

C

HC

CH

HC

HC

CH 2O PO 32

O O

O H

HO

O H

O H

N AD PH + H +

NADP + H 2O H +

1

2

3

4

5

6

G lucose-6-phosphate D ehydrogenase

6-Phospho- glucono-lactonase

glucose-6-phosphate 6-phoshogluconolactone 6-phosphogluconate

Phosphogluconate Dehydrogenase catalyzes oxidative decarboxylation 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+ serves as oxidant

C

HC

CH

HC

HC

CH 2OPO 32

O O

OH

HO

OH

OH

1

2

3

4

5

6

CH 2OH

C

HC

HC

CH 2OPO 32

OH

OH

1

2

3

4

5

ONADP + NADPH + H+

CO 2

Phosphogluconate Dehydrogenase

6-phosphogluconate ribulose-5-phosphate

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 are reversible

C

C

C

CH2OPO32

O

OHH

OHH

CH2OH

C

C

C

CH2OPO32

O

HHO

OHH

CH2OH

C

C

C

CH2OPO32

OH

OHH

OHH

HC O

H

ribulose-5- phosphate

xylulose-5- phosphate

ribose-5- phosphate

Epimerase

Isomerase

Transketolase transfers a 2-C fragment from xylulose-5-P to either ribose-5-P or erythrose-4-P

C

C

C

CH 2O P O 32

O

HHO

OHH

CH 2O H

C

C

C

CH 2O P O 32

OH

OHH

OHH

HC O

H C

C

C

CH 2O P O 32

OH

OHH

OHH

C H

H

HC

C

CH 2O P O 32

O

OHH

C

CH 2O H

O

HO

+ +

x y lu lo se - r ib o se - g ly c e ra ld e h y d e - se d o h e p tu lo se - 5 -p h o sp h a te 5 -p h o sp h a te 3 -p h o sp h a te 7 -p h o sp h a te

T ran sk e to la se

Transfer of the 2-C fragment to the 5-C aldose ribose-5-phosphate yields sedoheptulose-7-phosphate

Transfer of the 2-C fragment instead to the 4-C aldose erythrose-4-phosphate yields fructose-6-phosphate

C

C

C

CH 2O P O 32

O

HHO

OHH

CH 2O H

C

C

C

CH 2O P O 32

OH

OHH

OHH

HC O

H C

C

C

CH 2O P O 32

OH

OHH

OHH

C H

H

HC

C

CH 2O P O 32

O

OHH

C

CH 2O H

O

HO

+ +

x y lu lo se - r ib o se - g ly c e ra ld e h y d e - se d o h e p tu lo se - 5 -p h o sp h a te 5 -p h o sp h a te 3 -p h o sp h a te 7 -p h o sp h a te

T ran sk e to la se

Transaldolase catalyzes transfer of a 3-C dihydroxyacetone moiety, from sedoheptulose-7-phosphate to glyceraldehyde-3-phosphate

C H 2 O H

C

C H

HC

HC

HC

H 2 C

O H

O H

O PO 32

O H

H O

O

HC

HC

HC

H 2 C

O

O H

O PO 32

O H

HC

HC

H 2 C

O

O PO 32

O H

H 2 C

C

C H

HC

HC

H 2 C

O H

O PO 32

O H

O H

H O

O

se d o h e p tu lo se - g ly c e ra ld e h y d e - e ry th ro se - f ru c to se - 7 -p h o sp h a te 3 -p h o sp h a te 4 -p h o sp h a te 6 -p h o sp h a te

T ra n sa ld o la se

+ +