Greiner Jack V, Snogren Tamara I, Glonek Thomas
Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Schepens Eye Research Institute of Massachusetts Eye & Ear, Boston, MA 02114, USA.
Biology (Basel). 2025 Feb 2;14(2):152. doi: 10.3390/biology14020152.
The phosphorus-31 (P) spectral modulus (PSM) is a measure of the metabolic status of cells, tissues, and organs. The PSM can be calculated from P nuclear magnetic resonance (P NMR) spectra obtained from cell, tissue, or organ preparations. These P NMR spectra can be a measure of intact living cells, tissues, or organs, or appropriate biochemical extracts of such preparations. The P NMR spectrum is comprised of signals derived from organophosphate metabolites that resonate from 10 δ to -25 δ on the phosphorus chemical shift δ scale. The PSM is the ratio of the high-energy phosphate to that of the low-energy phosphate spectral integrals. These integrals may be conveniently grouped into high-energy and low-energy spectral regions, respectively, into P chemical shifts located between -0.13 δ to -25 δ and between 10 δ to -0.13 δ. High-energy phosphates are typically described as providing the energy necessary for the activity of cellular metabolism; chemically, they contain one or more phosphate anhydride bonds. This study demonstrates that, (1) in general, the higher the metabolic activity, the higher the PSM, and (2) the modulus calculation does not require a highly resolved P spectrum and can be calculated solely from the integral. The PSM was calculated among cells, tissues, and organs considered normal, diseased, and stressed. In diseased (mean 1.29 ± 0.73) and stressed (mean 1.23 ± 0.75) cells, tissues, and organs, PSM values are typically low or low relative to normal cells, tissues, or organs (mean 1.65 ± 0.90), following time-course measurements, in dynamic decline. The PSM is useful in determining the metabolic status of cells, tissues, or organs and can be employed as a calculable numeric assay for determining health status statically or over time. Calculation of the PSM can be carried out with spectra of low signal-to-noise; it relies on the minimal resolution required to detect an integral curve having a clear spectral integral inflection point at ca. -0.13 δ. Detection of an integral curve alone enables the calculation of a PSM even at levels of phosphorus concentration so low as to prevent detection of the individual or groups of metabolites, such as with in vivo or ex vivo cell, tissue, or organ determinations. This study (1) presents the foundations and fundamentals of the PSM, a living index of tissue metabolic health, and (2) demonstrates the use of spectral scan analysis in opening new vistas of biology and medicine for measuring the metabolic status of stressed and diseased tissues at a range of detectable levels for monitoring therapeutic interventions.
磷-31(P)光谱模量(PSM)是衡量细胞、组织和器官代谢状态的指标。PSM可根据从细胞、组织或器官制剂获得的P核磁共振(P NMR)光谱计算得出。这些P NMR光谱可以是完整活细胞、组织或器官的指标,也可以是此类制剂的适当生化提取物的指标。P NMR光谱由源自有机磷酸代谢物的信号组成,这些信号在磷化学位移δ标度上从10δ到-25δ处共振。PSM是高能磷酸盐与低能磷酸盐光谱积分的比值。这些积分可分别方便地分为高能和低能光谱区域,即位于-0.13δ至-25δ之间以及10δ至-0.13δ之间的P化学位移。高能磷酸盐通常被描述为提供细胞代谢活动所需的能量;从化学角度来看,它们含有一个或多个磷酸酐键。本研究表明,(1)一般而言,代谢活性越高,PSM越高;(2)模量计算不需要高分辨率的P光谱,仅根据积分即可计算。在被认为正常、患病和应激的细胞、组织和器官中计算PSM。在患病(平均值1.29±0.73)和应激(平均值1.23±0.75)的细胞、组织和器官中,经过时间进程测量,PSM值通常较低,或相对于正常细胞、组织或器官(平均值1.65±0.90)处于动态下降状态。PSM有助于确定细胞、组织或器官的代谢状态,可作为一种可计算的数值测定方法,用于静态或长期确定健康状态。PSM的计算可以使用低信噪比的光谱进行;它依赖于检测在约-0.13δ处具有清晰光谱积分拐点的积分曲线所需的最低分辨率。仅检测积分曲线就能够计算PSM,即使在磷浓度低至无法检测到单个或成组代谢物的水平时也能如此,例如在体内或体外细胞、组织或器官测定中。本研究(1)介绍了PSM(一种组织代谢健康的活体指标)的基础和基本原理,(2)展示了光谱扫描分析在为生物学和医学开辟新视野方面的应用,可以在一系列可检测水平上测量应激和患病组织的代谢状态,以监测治疗干预效果。