A Short Review on Biochemistry

Pentose Phosphate Pathway

…anabolic pathway that utilizes the 6 carbons of glucose to generate 5 carbon sugars and reducing equivalents.

…this pathway, under certain conditions, can completely oxidize glucose to CO2 and water

also called Phosphogluconate Pathway or Hexose Monophosphate Shunt

♠ It occurs in the cytosol!

♠ It does not lead to production of ATP!

♠ It is more complex than glycolysis

Uses of NADPH

…in the cell is to prevent oxidative stress

*It reduces the coenzyme glutathione which converts reactive H2O2 into H2O.

*If absent, the H2O2 would be converted to hydroxyl free radicals which can attack the cell.

*It is also used to generate hydrogen peroxide for phagocytes

♦NADPH wa product of the Pentose Phosphate Pathway, functions as a reductant in anabolic (synthetic) pathways, e.g., fatty acid synthesis. wThe reactions of fatty acid biosynthesis and steroid biosynthesis utilize large amounts of NADPH.

♦NAD+ wserves as electron acceptor in catabolic pathways, in which metabolites are oxidized.

*NAD+ & NADP+ differ only in the presence of an extra phosphate on the adenosine ribose of NADP+. This difference has little to do with redox activity, but is recognized by substrate-binding sites  of enzymes. It is a mechanism for separation of catabolic and synthetic pathways.

*Additionally, erythrocytes utilize the reactions of the PPP to generate large amounts of NADPH used in the reduction of glutathione. The conversion of ribonucleotides to deoxyribonucleotides (through the action of ribonucleotide reductase) requires NADPH as the electron source ütherefore, any rapidly proliferating cell needs large quantities of NADPH.

Again, the active tissues that uses NADPH:

–> liver, adipose tissue, adrenal cortex, thyroid, RBC, lactating mammary gland

♠The PPP supplies the RBC with NADPH to maintain the reduced state of glutathione.

♠The inability to maintain reduced glutathione in RBCs leads to increased accumulation of peroxides, predominantly H2O2, that in turn results in a weakening of the cell wall and concomitant hemolysis.

♠Accumulation of H2O2 also leads to increased rates of oxidation of hemoglobin to methemoglobin that also weakens the cell wall.

♠Glutathione removes peroxides via the action of glutathione peroxidase.

♠The PPP in erythrocytes is essentially the only pathway for these cells to produce NADPH.

Primary Functions of Pentose Phosphate Pathway

1. To generate reducing equivalents, in the form of NADPH, for reductive biosynthesis reactions within cells.

2. To provide the cell with ribose-5-phosphate (R5P) for the synthesis of the nucleotides and nucleic acids.

Note:  Although not a significant function of the PPP, it can operate to metabolize dietary pentose sugars derived from the digestion of nucleic acids as well as to rearrange the carbon skeletons of dietary carbohydrates into glycolytic/gluconeogenic intermediates.