Question

Write down the equation for the production of NADPH and Ribose-5-P in the Pentose Phosphate Pathway(PPP) and the PPP's biological significance :)

Answer 1

The pentose Phosphate pathway (the hexose monophosphate shunt) :

The pentose pathway could be divided into two phases: (1) oxidative phase, (2) non-oxidative phase.

Oxidative phase :

In oxidative phase of the pentose pathway is glucose-6-P oxidized to ribulose-5-P, CO₂ is released, 2 NADPH are produced. Overall equation:

The overall reaction for this process is:

Glucose 6-phosphate + 2 NADP⁺ + H₂O ? ribulose 5-phosphate + 2 NADPH + 2 H⁺ + CO₂

Reactants	Products	Enzyme
Glucose 6-phosphate+ NADP+	? 6-phosphoglucono-?-lactone + NADPH	glucose 6-phosphate dehydrogenase
6-phosphoglucono-?-lactone + H2O	? 6-phosphogluconate+ H+	6-phosphogluconolactonase
6-phosphogluconate + NADP+	? ribulose 5-phosphate + NADPH + CO2	6-phosphogluconate dehydrogenase

Glucose-6-phosphate (1), 6-phosphoglucono-?-lactone (2), 6-phosphogluconate (3), ribulose 5-phosphate (4)

Non-oxidative phase :

In the non-oxidative phase reciprocal conversions of the phosphorylated monosaccharides take place. These reactions are freely reversible. Basic scheme of the non-oxidative phase of the pentose pathway is as follows:

Net reaction:

3 ribulose-5-phosphate ? 1 ribose-5-phosphate + 2 xylulose-5-phosphate ? 2 fructose-6-phosphate + glyceraldehyde-3-phosphate

Reactants	Products	Enzymes
ribulose 5-phosphate	? ribose 5-phosphate	Ribose-5-phosphate isomerase
ribose 5-phosphate	? xylulose 5-phosphate	Ribulose 5-Phosphate 3-Epimerase
xylulose 5-phosphate + ribose 5-phosphate	? glyceraldehyde 3-phosphate + sedoheptulose 7-phosphate	transketolase
sedoheptulose 7-phosphate + glyceraldehyde 3-phosphate	? erythrose 4-phosphate + fructose 6-phosphate	transaldolase
xylulose 5-phosphate + erythrose 4-phosphate	? glyceraldehyde 3-phosphate + fructose 6-phosphate	transketolase

Significance of Pentose-Phosphate-Pathway:

(i) It provides alternative route for carbohydrate breakdown.

(ii) It generates NADPH molecules which are used as reductants in biosynthetic processes under conditions when NADPH molecules are not generated by photosynthesis. It is therefore, especially important in non-photosynthetic tissues such as in differentiating tissues, ger­minating seeds and during periods of darkness. Production of NADPH is not linked to ATP generation in pentose phosphate pathway.

(iii) It provides Ribose sugars for the synthesis of nucleic acids.

(iv) It plays important role in fixation of CO₂ in photosynthesis through Ribulose-5-Phosphate. (Ribulose 1, 5-bisphosphate derived from Ribulose-5-Phosphate is the primary acceptor of CO₂ in photosynthesis).

(v) It provides Erythrose-4-phosphate which is required for the synthesis of shikimic acid. The latter is precursor of aromatic ring compounds.

(In addition to the above pathway for the oxidation of carbohydrates, still other routes have been identified in some micro-organisms and enzyme systems discovered. In all such cases the initial steps of glucose oxidation differ from glycolysis but ultimately pyruvic acid is produced.

The pentose Phosphate pathway

The pentose pathway is localized in cytosol. Predominantly in hepatocytes, adipocytes, testicle cells, adrenal cells, erythrocytes, lactating mammary gland. Enzymes for this metabolic pathway however are in every tissue.

The pentose pathway is capable of direct glucose oxidation to CO₂ without involving the TCA cycle and the ETC. Oxidation requires dehydrogenases. Dehydrogenases require co-factors.

In the pentose pathway as co-factors act NADP⁺. NADP⁺ accepts reducing equivalents and NADPH is thus produced.

NADPH has many functions. NADPH for example (1) is source of reducing equivalents in some biosynthetic pathways (fatty acids synthesis, steroids synthesis, etc…), (2) acts in antioxidant defence of the cells (e.g. glutathione (GSH) synthesis), or (3) acts in biotransformation reactions.

The pentose pathway also produces (in further steps) ribose-5-P (ribose-5-P is precursor in nucleic acids synthesis) or other monosaccharides.

The main functions of the pentose pathway:

1) NADPH production – The pentose pathway is the most important source of NADPH in cells.

2) Ribose-5-P (Rib-5-P) production

3) Reciprocal conversion of monosaccharides – it is important e.g. in glycoproteins synthesis