Oxidative reactions of the pentose phosphate pathway
One form of chemical energy used to drive biosynthetic reactions forward is the reducing power of the energy carrier NADPH. NADPH is essential to drive the biosynthesis of fatty acids and cholesterol for example. While NADPH is an important energy carrier and is closely related to the high-energy electron carrier NADH, NADPH is distinct from NADH in several ways. NADH in oxidative phosphorylation in mitochondria transports chemical energy from the Kreb's cycle to the electron transport chain, but NADPH does not play this role. The cell keeps its pools of NADH and NADPH isolated biochemically, through the specificity of the enzymes that use and generate these cofactors. Enzymes that metabolize NADH and NADPH are highly specific for one cofactor or the other and are in different pathways. While NADH is produced in mitochondria by the Kreb's cycle, NADPH is produced through a pathway called the pentose phosphate pathway. Since one of the main purposes of this pathway is to produce NADPH for biosynthesis, this pathway occurs most predominantly in tissues like liver, fat cells, or adrenal glands that are involved in fatty acid and cholesterol biosynthesis. This pathway starts with glucose-6-phosphate, the first committed step in glycolysis, and can provide an alternative route to glycolysis for energy production. The first portion of the pentose phosphate pathway involves the oxidation of glucose in three steps, with the concomitant production of NADPH. The first step in the pentose phosphate pathway is catalyzed by glucose-6-phosphate dehydrogenase. In normal red blood cells, the NADPH produced by glucose-6-phosphate dehydrogenase is used to regenerate glutathione and protect cell membranes. Genetic deficiency in the activity of this enzyme is very common in some populations, and can result in anemias caused by fragile red blood cells. In the second and third steps, further oxidation makes more NADPH and releases carbon dioxide, shortening the sugar from six carbons to five (D-ribulose 5-phosphate).After isomerization, D-ribose 5-phosphate is produced and provides the starting point for a series of reactions that converts the 5-carbon ribose into 6-carbon fructose-6-phosphate and 3-carbon glyceraldehyde-3-phosphate. Ribose is also used to make nucleotides for RNA and DNA.
