Hezel M P, Weitzberg E
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Oral Dis. 2015 Jan;21(1):7-16. doi: 10.1111/odi.12157. Epub 2013 Jul 10.
The tiny radical nitric oxide (NO) participates in a vast number of physiological functions including vasodilation, nerve transmission, host defence and cellular energetics. Classically produced by a family of specific enzymes, NO synthases (NOSs), NO signals via reactions with other radicals or transition metals. An alternative pathway for the generation of NO is the nitrate-nitrite-NO pathway in which the inorganic anions nitrate (NO(3)(-)) and nitrite (NO(2)(-)) are reduced to NO and other reactive nitrogen intermediates. Nitrate and nitrite are oxidation products from NOS-dependent NO generation but also constituents in our diet, mainly in leafy green vegetables. Irrespective of origin, active uptake of circulating nitrate in the salivary glands, excretion in saliva and subsequent reduction to nitrite by oral commensal bacteria are all necessary steps for further NO generation. This central role of the oral cavity in regulating NO generation from nitrate presents a new and intriguing aspect of the human microbiome in health and disease. In this review, we present recent advances in our understanding of the nitrate-nitrite-NO pathway and specifically highlight the importance of the oral cavity as a hub for its function.
微小的自由基一氧化氮（NO）参与大量生理功能，包括血管舒张、神经传递、宿主防御和细胞能量代谢。传统上，NO由一类特定的酶——一氧化氮合酶（NOSs）产生，它通过与其他自由基或过渡金属反应来传递信号。产生NO的另一条途径是硝酸盐-亚硝酸盐-NO途径，其中无机阴离子硝酸盐（NO₃⁻）和亚硝酸盐（NO₂⁻）被还原为NO和其他活性氮中间体。硝酸盐和亚硝酸盐是NOS依赖的NO生成的氧化产物，但也是我们饮食中的成分，主要存在于绿叶蔬菜中。无论来源如何，唾液腺对循环硝酸盐的主动摄取、唾液中的排泄以及随后口腔共生细菌将其还原为亚硝酸盐，都是进一步生成NO的必要步骤。口腔在调节硝酸盐生成NO方面的这一核心作用，为人类微生物群在健康和疾病中的作用展现了一个新的、引人入胜的方面。在这篇综述中，我们介绍了我们对硝酸盐-亚硝酸盐-NO途径理解的最新进展，并特别强调了口腔作为其功能枢纽的重要性。
