Summary 09032021

Pentose phosphate pathway

References

Baynes, W. & Dominiczak, M. (2014). Medical Biochemistry (4th ed.). Elsevier.

Ge, T., Yang, J., Zhou, S., Wang, Y. Li, Y. & Tong, X. (2020). The Role of the Pentose Phosphate Pathway in Diabetes and Cancer. Frontiers in endocrinology, 11.

Rodwell, V., Bender, D., Botham, K., Kennelly, P. & Weil, P. (2018). Harper Illustrated Biochemistry (31st ed.). McGraw Hill Education.

Biochemistry I

Paola Pimiento

It produces:

It can transport carbons back to the glycolytic or gluconeogenic pathway.

It is important to keep redox homeostasis.

Also known as the hexose monophosphate shunt.

It relevant for glucose metabolism.

It does not provide ATP.

Essential for cell survival and proliferation.

It is important for nucleic acid synthesis.

NADPH

Ribose 5-phosphate (R5P)

Needed for synthesis of fatty acids, sterols, nucleotides, and non-essential amino acids.

It can be oxidative or non-oxidative.

It happens on the cytosol.

Regulation:

Glucose 6-phosphate dehydrogenase

It has many participants listed like:

Substrates

Enzymes

Products

It is present in all cells.

It branches from glycolysis at the level of Glucose-6-phosphate.

When this pathway is not needed, its intermediates go back to glycolysis as Fructose-6-phosphate and Glyceraldehyde-3-phosphate.

It is used in redox reactions.

It is used in the liver for detoxification and excretion of drugs.

It has 2 stages:

Irreversible redox stage

Reversible interconversion stage

Important in red blood cells.

Glucose-6-phosphate

Step 1

Glucose-6-phosphate dehydrogenase

Transformed by oxidation.

6-phosphogluconic acid lactone

Step 2

6-phosphogluconic acid lactone

It is a cyclic sugar ester.

Lactonase

Transformed by hydrolyzation.

6-phosphogluconic acid

Step 3

6-phosphogluconic acid

NADPH

6-phosphoglutonate dehydrogenase

Transformed by oxidative decarboxylation.

NADPH

Ribulose-5-phosphate

CO2

6-phosphoglutonate dehydrogenase

These keep a NAD+/NADPH cytoplasmatic ratio of approximately 100.

Glycolytic enzymes only use NADH, and pentose phosphate pathway only uses NADPH.

Cells with active nucleic acid synthesis

Ribulose-5-phosphate

Ribose-5-phosphate

Nondividing cells

Pentose phosphates are rerouted to glycolysis.

Fructose-6-phosphate

Glyceraldehyde-3-phosphate

It follows this pathway:

Ribulose-5-phosphate

Ribulose-5-phosphate epimerase

Xylulose-5-phosphate

It alters the third carbon to turn it into an epimer.

Step 1

Step 2

Ribulose-5-phosphate

Ribose-5-phosphate isomerase

Ribose-5-phosphate

Xylulose-5-phosphate

Ribose-5-phosphate

Transketolase

It transfers 2 carbons from the xylulose-5-phosphate to the ribose-5-phosphate.

Sedoheptulose-7-phosphate

Glyceraldehyde-3-phosphate

Step 3

Sedoheptulose-7-phosphate

Glyceraldehyde-3-phosphate

Transaldolase

It transfers the dihydroxyacetone (3 carbons) from the sedoheptulose-7-phosphate to the glyceraldehyde 3-phosphate.

Fructose-6-phosphate

Erythrose-4-phosphate

Step 4

Erythrose-4-phosphate

Xylulose-5-phosphate

Transketolase

The xylulose-5-phosphate acts as a donor of a glycolaldehyde group.

Fructose-6-phosphate

Glyceraldehyde-3-phosphate

To completely oxidize glucose to CO2, enzymes present on the cytosol must turn glyceraldehyde-3-phosphate to glucose-6-phosphate.

This implies a reverse process of glycolysis and it needs the enzyme fructose 1,6-bisphosphatase.

If this process cannot be done, the glyceraldehyde-3-phosphate will follow the glycolysis pathway.

Glycolysis and this pathway are connected.

It activates the phosphatase that dephosphorylates fructose 1,6-bisphosphatase

Xylulose-5-phosphate

This increases the production of fructose 1,6-bisphosphate.

It also increases phosphofructokinase 1 activity.

It activates the phosphatase protein that initiates nuclear translocation.

This increases fatty acid synthesis.

The NADPH is needed by glutathione peroxidase which protects them from hemolysis.

It could be targeted to help treat conditions such as:

Insulin resistance related to obesity.

Chronic diabetic complications.

Cancer