Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany.
Nat Metab. 2023 Aug;5(8):1275-1289. doi: 10.1038/s42255-023-00863-2. Epub 2023 Aug 23.
The pentose phosphate pathway (PPP) is a glucose-oxidizing pathway that runs in parallel to upper glycolysis to produce ribose 5-phosphate and nicotinamide adenine dinucleotide phosphate (NADPH). Ribose 5-phosphate is used for nucleotide synthesis, while NADPH is involved in redox homoeostasis as well as in promoting biosynthetic processes, such as the synthesis of tetrahydrofolate, deoxyribonucleotides, proline, fatty acids and cholesterol. Through NADPH, the PPP plays a critical role in suppressing oxidative stress, including in certain cancers, in which PPP inhibition may be therapeutically useful. Conversely, PPP-derived NADPH also supports purposeful cellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) for signalling and pathogen killing. Genetic deficiencies in the PPP occur relatively commonly in the committed pathway enzyme glucose-6-phosphate dehydrogenase (G6PD). G6PD deficiency typically manifests as haemolytic anaemia due to red cell oxidative damage but, in severe cases, also results in infections due to lack of leucocyte oxidative burst, highlighting the dual redox roles of the pathway in free radical production and detoxification. This Review discusses the PPP in mammals, covering its roles in biochemistry, physiology and disease.
戊糖磷酸途径（PPP）是一条葡萄糖氧化途径，与上糖酵解平行运行，产生 5-磷酸核糖和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）。5-磷酸核糖用于核苷酸合成，而 NADPH 参与氧化还原平衡以及促进生物合成过程，如四氢叶酸、脱氧核苷酸、脯氨酸、脂肪酸和胆固醇的合成。通过 NADPH，PPP 在抑制氧化应激方面发挥着关键作用，包括在某些癌症中，PPP 抑制可能具有治疗意义。相反，PPP 衍生的 NADPH 也支持细胞有目的地产生活性氧（ROS）和活性氮（RNS）用于信号传递和病原体杀伤。在葡萄糖-6-磷酸脱氢酶（G6PD）等定向途径酶中，PPP 的遗传缺陷相对常见。G6PD 缺乏症通常表现为由于红细胞氧化损伤导致的溶血性贫血，但在严重情况下，也会因白细胞氧化爆发缺乏而导致感染，突出了该途径在自由基产生和解毒方面的双重氧化还原作用。这篇综述讨论了哺乳动物中的 PPP，涵盖了其在生物化学、生理学和疾病中的作用。
