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Phosphate Metabolism in Health and Disease.
Calcified Tissue International ( IF 4.2 ) Pub Date : 2020-04-07 , DOI: 10.1007/s00223-020-00686-3
Munro Peacock 1
Affiliation  

Phosphorus, a 5A element with atomic weight of 31, comprises just over 0.6% of the composition by weight of plants and animals. Three isotopes are available for studying phosphorus metabolism and kinetics. 31P is stable, whereas the radioactive isotope 33P has a half-life of 25 days and 32P has a half-life of 14 days. Phosphate ester and phosphoanhydride are common chemical linkages and phosphorus is a key element in organic molecules involved in a wide variety of essential cellular functions. These include biochemical energy transfer via adenosine triphosphate (ATP), maintenance of genetic information with nucleotides DNA and RNA, intracellular signaling via cyclic adenosine monophosphate (cAMP), and membrane structural integrity via glycerophospholipids. However, this review focuses on the metabolism of inorganic phosphorus (Pi) acting as a weak acid. Phosphoric acid has all three hydrogens attached to oxygen and is a weak diprotic acid. It has 3 pKa values: pH 2.2, pH 7.2, and pH 12.7. At physiological pH of 7.4, Pi exists as both H2PO4(-) and HPO4(2-) and acts as an extracellular fluid (ECF) buffer. Pi is the form transported across tissue compartments and cells. Measurement of Pi in biological fluids is based on its reaction with ammonium molybdate which does not measure organic phosphorus. In humans, 80% of the body phosphorus is present in the form of calcium phosphate crystals (apatite) that confer hardness to bone and teeth, and function as the major phosphorus reservoir (Fig. 1). The remainder is present in soft tissues and ECF. Dietary phosphorus, comprising both inorganic and organic forms, is digested in the upper gastrointestinal tract. Absorbed Pi is transported to and from bone, skeletal muscle and soft tissues, and kidney at rates determined by ECF Pi concentration, rate of blood flow, and activity of cell Pi transporters (Fig. 2). During growth, there is net accretion of phosphorus, and with aging, net loss of phosphorus occurs. The bone phosphorus reservoir is depleted and repleted by overall phosphorus requirement. Skeletal muscle is rich in phosphorus used in essential biochemical energy transfer. Kidney is the main regulator of ECF Pi concentration by virtue of having a tubular maximum reabsorptive capacity for Pi (TmPi) that is under close endocrine control. It is also the main excretory pathway for Pi surplus which is passed in urine. Transcellular and paracellular Pi transports are performed by a number of transport mechanisms widely distributed in tissues, and particularly important in gut, bone, and kidney. Pi transporters are regulated by a hormonal axis comprising fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and 1,25 dihydroxy vitamin D (1,25D). Pi and calcium (Ca) metabolism are intimately interrelated, and clinically neither can be considered in isolation. Diseases of Pi metabolism affect bone as osteomalacia/rickets, soft tissues as ectopic mineralization, skeletal muscle as myopathy, and kidney as nephrocalcinosis and urinary stone formation.Fig. 1Content of phosphorus in human adult: skeleton, soft tissue, and extracellular fluid (grams, log scale). Corresponding data for calcium are shown for comparisonFig. 2Phosphate (Pi) transport to and from tissue compartments in mg/24 h. At a dietary phosphorus of 1400 mg, 1120 mg is absorbed in upper intestine to the ECF, 210 mg returned to intestine by endogenous secretion, resulting in 910 mg net Pi absorption and 490 mg fecal excretion. At bone, 180 mg is deposited by bone formation and 180 mg return to the ECF by bone resorption. At kidney, 5040 mg is filtered at the glomerulus and 4130 mg return to the ECF by tubular reabsorption with 910 mg excreted in the urine. In soft tissue, Pi is exchanged between ECF and cells.

中文翻译:

健康与疾病中的磷酸盐代谢。

磷是原子量为31的5A元素,占植物和动物重量的0.6%以上。三种同位素可用于研究磷的代谢和动力学。31P是稳定的,而放射性同位素33P的半衰期为25天,而32P的半衰期为14天。磷酸酯和磷酸酐是常见的化学键,磷是参与多种基本细胞功能的有机分子的关键元素。这些措施包括通过三磷酸腺苷(ATP)进行生化能量转移,通过核苷酸DNA和RNA维持遗传信息,通过环状单磷酸腺苷(cAMP)进行细胞内信号传递以及通过甘油磷脂实现膜结构完整性。然而,这篇综述着重于无机磷(Pi)作为弱酸的代谢。磷酸具有与氧连接的所有三个氢,是弱的二质子酸。它具有3个pKa值:pH 2.2,pH 7.2和pH 12.7。在7.4的生理pH下,Pi以H2PO4(-)和HPO4(2-)的形式存在,并充当细胞外液(ECF)缓冲液。Pi是跨组织隔室和细胞运输的形式。生物流体中Pi的测量基于其与不测量有机磷的钼酸铵的反应。在人类中,体内80%的磷以磷酸钙晶体(磷灰石)的形式存在,赋予骨骼和牙齿以硬度,并作为主要的磷储库(图1)。其余部分存在于软组织和ECF中。膳食磷,包括无机形式和有机形式,在上消化道被消化。吸收的Pi以ECF Pi浓度,血流速率和细胞Pi转运蛋白活性确定的速率在骨骼,骨骼肌和软组织以及肾脏之间来回运输(图2)。在生长过程中,会净积累磷,随着年龄的增长,会发生磷的净损失。骨磷储库被总磷需求所消耗和补充。骨骼肌富含用于基本生化能量转移的磷。肾脏由于在严格的内分泌控制下具有管状的最大Pi吸收能力(TmPi),因此是ECF Pi浓度的主要调节剂。这也是通过尿液传播的剩余磷的主要排泄途径。跨细胞和旁细胞的Pi转运是通过许多广泛分布于组织中的转运机制进行的,在肠道,骨骼和肾脏中尤为重要。Pi转运蛋白受包含成纤维细胞生长因子23(FGF23),甲状旁腺激素(PTH)和1,25二羟基维生素D(1,25D)的激素轴调节。Pi和钙(Ca)的代谢密切相关,在临床上都不能单独考虑。Pi代谢疾病会影响骨骼(如骨软化症/ rick病),软组织(如异位矿化),骨骼肌(如肌病)和肾脏(如肾钙化病和尿路结石)。1成人中磷的含量:骨骼,软组织和细胞外液(克,对数刻度)。显示了钙的相应数据用于比较。2磷酸盐(Pi)在mg / 24小时内往返于组织隔室。饮食中的磷为1400 mg时,其上肠经ECF吸收了1120 mg,内源性分泌物使210 mg返回肠,导致净Pi吸收为910 mg,粪便排泄为490 mg。在骨骼处,通过骨骼形成沉积180 mg,通过骨骼吸收将180 mg返回ECF。在肾脏,肾小球滤过5040 mg,通过肾小管重吸收(尿中排出910 mg)使4130 mg返回ECF。在软组织中,Pi在ECF和细胞之间交换。180 mg通过骨形成沉积,180 mg通过骨吸收返回ECF。在肾脏,肾小球滤过5040 mg,通过肾小管重吸收(尿中排出910 mg)使4130 mg返回ECF。在软组织中,Pi在ECF和细胞之间交换。180 mg通过骨形成沉积,180 mg通过骨吸收返回ECF。在肾脏,肾小球滤过5040 mg,通过肾小管重吸收(尿中排出910 mg)使4130 mg返回ECF。在软组织中,Pi在ECF和细胞之间交换。
更新日期:2020-04-20
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