Pentose Phosphate Pathway in Disease and Therapy

Pentose phosphate (PP) pathway, which is ubiquitously present in all living organisms, is one of the major metabolic pathways associated with glucose metabolism. The most important functions of this pathway includes the generation of reducing equivalents in the form of NADPH for reductive biosynthesis, and production of ribose sugars for the biosynthesis of nucleotides, amino acids, and other macromolecules required by all living cells. Under normal conditions of growth, PP pathway is important for cell cycle progression, myelin formation, and the maintenance of the structure and function of brain, liver, cortex and other organs. Under diseased conditions, such as in cases of many metabolic, neurological or malignant diseases, pathological mechanisms augment due to defects in the PP pathway genes. Adoption of alternative metabolic pathways by cells that are metabolically abnormal, or malignant cells that are resistant to chemotherapeutic drugs often plays important roles in disease progression and severity. Accordingly, the PP pathway has been suggested to play critical roles in protecting cancer or abnormal cells by providing reduced environment, to protect cells from oxidative damage and generating structural components for nucleic acids biosynthesis. Novel drugs that targets one or more components of the PP pathway could potentially serve to overcome challenges associated with currently available therapeutic options for many metabolic and non-metabolic diseases. However, careful designing of drugs is critical that takes into the accounts of cell’s broader genomic, proteomic and metabolic contexts under consideration, in order to avoid undesirable side-effects. In this review, we discuss the role of PP pathway under normal and abnormal physiological conditions and the potential of the PP pathway as a target for new drug development to treat metabolic and non-metabolic diseases.