Pentose Phosphate

• The intermediate R5P in the PPP is a precursor for nucleotide biosynthesis, which is essential for DNA replication and DNA damage repair.
• Pentose phosphate pathway, also known as Hexose monophosphate shunt, Phosphogluconate pathway, occurs in the cytosol.
• One fate of G6P is the pentose pathway.
• The pentose pathway is a shunt that begins with the glycolytic intermediate glucose 6 - P and reconnects with glycolysis because two of the end products of the pentose pathway are glyceraldehyde 3 - P and fructose 6 - P.
• The pathway yields ribose 5 - phosphate which is used in nucleotide biosynthesis leading to DNA, RNA, and various cofactors (CoA, FAD, SAM, NAD+/NADP+).
• In general, with some exceptions, NADH is used to drive the phosphorylation of ADP to ATP.
• NADPH is used where reducing potential is required for synthetic reactions.
• The pentose pathway can be divided into two phases: non-oxidative interconversion of sugars and oxidative phosphorylation.
• NADPH + H+ is formed from two separate reactions: the glucose 6-phosphate DH (G6PD) reaction, which is the rate limiting step and is essentially irreversible, and the transketolase reaction.
• Cells have a greater need for NADPH than ribose 5 - phosphate.
• The enzyme is highly specific for NADP+; the Km for NAD+ is 1000 greater than for NADP+.
• The nonoxidative phase of the pentose pathway entails extensive carbon atom rearrangement.
• Transketolase requires the coenzyme thiamine pyrophosphate (TPP), the transaldolase does not.
• NADPH is a potent competitive inhibitor of the enzyme Glucose 6-phosphate dehydrogenase (G6PD).
• Glyceraldehyde 3 - phosphate, Fructose 6 - phosphate, Net result: 3C 5 D 2C 6 + C 3
• Glutathione is involved in amino
• The pentose phosphate pathway and its enzymes are not to be found in tissues that are not active in biosynthesis.
• Liver, for example, may feed up to 30% of its glucose through the pentose phosphate pathway.
• After weaning, these enzymes gradually disappear.
• More NADPH is needed than ribose 5-phosphate for fatty acid synthesis in adipose cells.
• As a mother’s body prepares to feed her offspring, the enzymes of the pentose phosphate pathway are switched on in the breast tissue.
• In tissues with active lipid biosynthesis such as liver, adrenal cortex, or lactating mammary glands, NADPH is used in redox reactions required for biosynthesis of cholesterol, bile salts, steroid hormones and triglycerides.
• Some tissues carry out active biosynthesis only intermittently.
• Ingested ribose can enter the glycolytic pathway through the pentose pathway.
• Adrenal cortex, constantly involved in biosynthesis of steroids, also needs NADPH.
• The distribution of PPP activity is important in the RBC and in non-dividing cells, where there is limited need for synthesis of DNA and RNA.
• Muscle, by contrast, is not a biosynthetic tissue, and therefore has no need of the PPP enzymes.
• Reduced glutathione (GSH) is a tripeptide composed of glutamate, cysteine, glycine.
• Reduced glutathione (GSH) maintains the normal reduced state of the cell.
• Glucose 6-phosphate dehydrogenase (G6PD) is the regulatory enzyme in the pentose phosphate pathway.
• The non-oxidative phase of the pentose phosphate pathway is used for the synthesis of ribose-5-phosphate for DNA/RNA building, also produced in the oxidative phase.
• Glutathione serves as a reductant.
• Rapidly dividing cells require more ribose 5-phosphate than NADPH.
• The need for NADPH and ribose 5-phosphate is balanced in some cells.
• Usually the ratio NADPH/NADP+ is high so the enzyme is inhibited.
• The oxidative phase of the pentose phosphate pathway involves the reduction of NADP+ to NADPH and the production of 1 H 2 O.
• With increased demand for NADPH, the ratio decreases and enzyme activity is stimulated.
• The liver also uses NADPH for hydroxylation reactions involved in the detoxification and excretion of drugs.
• Glutathione conjugates to drugs making them water soluble.
• Thiamine pyrophosphate (TPP) is required in reactions that require energy.