| THE PENTOSE PHOSPHATE PATHWAY
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| The pentose phosphate pathway is a cytosolic pathway present in all cells, so named because it is the primary pathway for formation of pentose phosphates for synthesis of nucleotides for polymerization into DNA and RNA. This pathway branches from glycolysis at the level of Glc-6-P, thus its alternative designation, the hexose monophosphate shunt. The pentose phosphate pathway is also described as a shunt, rather than a pathway, because, when pentoses are not needed for biosynthetic reactions, the pentose phosphate intermediates are recycled to the mainstream of glycolysis by conversion into Fru-6-P and glyceraldehyde-3-phosphate. This rerouting is especially important in the RBC and in non-dividing or quiescent cells, where there is limited need for synthesis of DNA and RNA.
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NADPH is a major product of the pentose phosphate pathway in all cells. In tissues with active lipid biosynthesis, e.g. liver, adrenal cortex or lactating mammary glands, the NADPH is used in redox reactions required for biosynthesis of fatty acids, cholesterol, steroid hormones, and bile salts. The liver also uses NADPH for hydroxylation reactions involved in the detoxification and excretion of drugs. The RBC has little biosynthetic activity, but still shunts about 10% of glucose through the pentose phosphate pathway, in this case almost exclusively for the production of NADPH. The NADPH is used primarily for the reduction of a cysteine-containing tripeptide
glutathione (GSH), an essential cofactor for antioxidant protection (Chapter 35).
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| The pentose phosphate pathway is divided into an irreversible redox stage, which yields both NADPH and pentose phosphates, and a reversible interconversion stage, in which excess pentose phosphates are converted into glycolytic intermediates. Both stages are important in the RBC, since it needs NADPH for reduction of glutathione, but has limited need for de novo synthesis of pentoses.
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