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NADPH is the reduced form of Nicotinamide Adenosine Dinucleotide Phosphate or NADP+. It is used in different reductive biosynthetic pathways where it acts as a reducing agent. Biosynthetic pathways such as fatty acid biosynthesis, cholesterol biosynthesis, hormone biosynthesis, etc. all use NADPH as a reducing agent. However, NADPH is synthesized by the reduction of NADP+. Pathways such as pentose phosphate pathway and the light reaction of photosynthesis produce NADPH by reducing NADP+.
Synthesis of the NADPH
- The light-dependent reaction of photosynthesis occurs in the stroma of the chloroplast. In that process, the photolysis of water molecules releases electrons for the reduction of NADP+ molecules. The production of NADPH is catalyzed by the Ferredoxin-NADP+ reductase (FNR).
- In the cytosol, The Pentose Phosphate Pathway produces NADPH. The enzymes for the production of NADPH are; 1) Glucose-6-Phosphate Dehydrogenase that catalyzes the conversion of glucose 6-phosphate to 6-phosphoglucono ∂-lactone and 2) 6-phospho-gluconate dehydrogenase that catalyzes the conversion of 6-phospho-gluconate into ribulose-5-phosphate.
Utilization of the NADPH
During the sphingolipid biosynthesis: 3-ketosphinganine reductase that catalyzes the reduction of 3-ketosphinganine (dehydrosphinganine) to sphinganine (dihydrosphingosine).
During cholesterol and bile acids biosynthesis: The following enzymes require NADPH as a source of electrons for the reduction reactions. These enzymes are;
- HMG-CoA reductase catalyzes the conversion of HMG-CoA into mevalonate.
- Squalene synthase catalyzes the condensation of two molecules of farnesyl pyrophosphate to form Squalene.
- Squalene monooxygenase that catalyzes the conversion of the Squalene into Squalene 2, 3-epoxide.
- Synthesis of cholyl-CoA and chenodeoxycholyl-CoA from 7-α-hydroxycholesterol.
In plants during the photosynthesis: In the stroma of chloroplast, glyceraldehyde 3-phosphate dehydrogenase requires NADPH that converts 1, 3-bisphosphoglycerate into glyceraldehyde 3-phosphate in the stroma of the chloroplast. In the mesophyllic cells of the C4 plants, malate dehydrogenase requires NADPH for the conversion of oxaloacetate to malate. Malate is then transported into the bundle sheath cells where it releases the CO2 for carbon fixation.
Steroid hormone biosynthesis also requires NADPH in some of the steps. In addition to that, Folate biosynthesis also needs NADPH, such as, N5, N10-methylenetetrahydrofolate dehydrogenase that catalyzes the interconversion of N5, N10-methyltetrahydrofolate into N5, N10-methylenetetrahydrofolate.
Amino acid biosynthesis: Glutamate synthase requires NADPH that catalyzes the conversion of α-ketoglutarate and glutamine into two molecules of glutamate. More than that, the reduction of glutathione disulfide to glutathione also requires NADPH as a source of electrons.