Piknova Barbora, Park Ji Won, Schechter Alan N
Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20852, USA.
Nutrients. 2025 Apr 30;17(9):1544. doi: 10.3390/nu17091544.
Homeostasis is the self-regulating processes in cells and organisms designed to maintain stability of the internal environment while adjusting to external changes. To achieve this dynamic stability, internal conditions oscillate within tightly regulated physiological tolerance limits. In mammals, maintaining nitric oxide (NO) availability appears crucial to sustain relatively constant blood flow into all organs and tissues. We hypothesize that NO homeostasis is one of the most important vital processes for warm-blooded animals. It is impossible to conserve the stability of most other vital substances, such as O, CO, blood sugar, pH, and temperature, to name just few, without well-functioning tissue perfusion. NO in mammals is generated either from L-arginine by nitric oxide synthases (NOSs) or by the reduction of nitrate (NO) to nitrite (NO) and NO by several proteins. Here we first discuss the organization of these two NO metabolic pathways, emphasizing that both pathways "cross" and "funnel" unused NO into the overall nitrate-nitrite-NO pathway. This pathway is cyclic, which gives nitrate a unique place in metabolism and predisposes it as a reservoir for NO. Then, we discuss the role of NO homeostasis that, by maintaining organ and tissue perfusion, supports and preserves constancy of other blood-delivered substances. This "governing" role of NO makes even clearer that the existence of NO storage and precursor molecules is necessary, to avoid NO shortages in cases of the precursor's or storage molecule's temporary unavailability, to ensure uninterrupted tissue access to NO. We propose that the skeletomuscular system and skin act as nitrate reservoirs assuring NO bioavailability at various external and internal conditions.
体内平衡是细胞和生物体中的自我调节过程，旨在维持内部环境的稳定性，同时适应外部变化。为实现这种动态稳定性，内部条件在严格调控的生理耐受限度内波动。在哺乳动物中，维持一氧化氮（NO）的可利用性对于维持相对恒定的血液流入所有器官和组织似乎至关重要。我们假设NO体内平衡是温血动物最重要的生命过程之一。如果没有正常运作的组织灌注，就不可能维持大多数其他重要物质的稳定性，如氧气、二氧化碳、血糖、pH值和温度等，仅举几例。哺乳动物体内的NO要么由一氧化氮合酶（NOSs）从L-精氨酸生成，要么由几种蛋白质将硝酸盐（NO₃⁻）还原为亚硝酸盐（NO₂⁻）并进一步还原为NO生成。在这里，我们首先讨论这两种NO代谢途径的组织，强调这两种途径都将未使用的NO“交叉”和“汇集”到整体硝酸盐-亚硝酸盐-NO途径中。该途径是循环的，这赋予了硝酸盐在代谢中独特的地位，并使其成为NO的储存库。然后，我们讨论NO体内平衡的作用，即通过维持器官和组织灌注，支持并保持其他血液输送物质的恒定。NO的这种“调控”作用更清楚地表明，NO储存和前体分子的存在是必要的，以避免在前体或储存分子暂时无法获得的情况下出现NO短缺，确保组织持续获得NO。我们提出，骨骼肌肉系统和皮肤充当硝酸盐储存库，确保在各种外部和内部条件下NO的生物利用度。
