NADPNADPHcyclend

NADPNADPH cycle, also known as the pentose phosphate pathway (PPP) or hexose monophosphate shunt, is a metabolic pathway parallel to glycolysis that occurs in nearly all living organisms. This cycle is crucial for maintaining cellular redox balance, synthesizing essential biomolecules, and providing precursors for nucleotide and amino acid production.

The cycle is divided into two phases: the oxidative phase and the non-oxidative phase. The oxidative phase begins with the oxidation of glucose-6-phosphate (G6P) by glucose-6-phosphate dehydrogenase (G6PD), producing 6-phosphogluconolactone and reducing NADP+ to NADPH. This step is irreversible and committed to the pathway. The lactone is then hydrolyzed by lactonase to form 6-phosphogluconate, which is further oxidized by 6-phosphogluconate dehydrogenase to ribulose-5-phosphate (Ru5P), releasing CO2 and generating another NADPH molecule.

The non-oxidative phase rearranges Ru5P and other intermediates to produce ribose-5-phosphate (R5P), a key precursor for nucleotide synthesis, as well as glyceraldehyde-3-phosphate (G3P) and erythrose-4-phosphate (E4P), which can re-enter glycolysis or be used in amino acid biosynthesis. The cycle also regenerates G6P, allowing it to re-enter the oxidative phase.

NADPH generated in the oxidative phase is vital for anabolic reactions, including fatty acid synthesis, cholesterol biosynthesis, and the reduction of glutathione in the detoxification of reactive oxygen species. The pathway is particularly active in cells with high biosynthetic demands, such as liver cells, adipocytes, and rapidly dividing cells like those in the bone marrow.

Genetic deficiencies in enzymes like G6PD can lead to hemolytic anemia, as red blood cells rely heavily on the PPP for NADPH production to maintain reduced glutathione levels and protect against oxidative damage. The cycle’s flexibility allows cells to balance energy production, redox homeostasis, and biosynthetic needs depending on metabolic demands.