What is Phosphate?
Phosphate, or PO43–, is an essential inorganic compound and is involved in a number of biochemical reactions and signaling pathways. The negative charge of phosphate ions allows them to participate in ionic and polar covalent bonds with other molecules and transfer large sums of energy between substrates.
Why is Phosphate Important?
Several key organic compounds contain phosphate. Nucleic acids such as DNA and RNA contain phosphate ions and are linked into polymeric chains by a type of chemical bond called phosphodiester bonds. Phosphate ions are also involved in the synthesis of essential lipids in the cell membrane [1], which serves as an essential barrier against the external environment and regulates the processes of cellular signaling and transport.
Energy-rich molecules like ATP and GTP also contain phosphate ions [1], which allows them to readily release energy by transferring phosphate groups.
Lastly, the transfer of phosphate molecules is a key process in various signaling pathways. The function of many proteins is regulated via phosphorylation and dephosphorylation, which is catalyzed by enzymes called kinases and phosphatases, respectively [1].
What Causes Low Phosphate Levels?
As various biochemical reactions occur within the body, serum phosphate levels fluctuate accordingly. Overall, phosphate levels tend to remain fairly stable thanks to mechanisms of homeostatic regulation. However, certain conditions may disrupt such homeostatic mechanisms and lead to abnormally low phosphate levels in the blood, or hypophosphatemia [2].
Low phosphatase levels in the body can be caused by several factors. Hypophosphatasia, a disorder due to pathogenic variants of the ALPL gene, is a common genetic cause of low serum alkaline phosphatase (ALP) levels [2,1]. Other causes can include severe acute injuries, diseases, drug therapy, malnutrition, vitamin and mineral deficiencies, and endocrine disorders [2]. Some patients may have unidentified mutations in regulatory regions of ALPL or abnormalities in other genes [2,3].
Main causes of low phosphate [2]:
- Inadequate phosphate intake. Inadequate phosphate intake may result from a prolonged phosphate-poor diet, poor intestinal absorption, or intestinal binding by exogenous agents such as medications.
- Excessive phosphate excretion. Excessive phosphate excretion may occur due to changes in renal function, such as those mediated by parathyroid hormone (PTH).
- Transfer of extracellular phosphate into the intracellular space. Intracellular shifting of phosphate can occur for several reasons. For example, refeeding syndrome can cause a rapid shift of extracellular phosphate into the intracellular space. Correction of hyperparathyroidism can also lead to such a shift, wherein phosphorous-deprived osteopenic bones begin to reabsorb phosphate from the extracellular space. Lastly, acute respiratory alkalosis may induce hypophosphatemia by raising pH, which increases the activity of an enzyme called phosphofructokinase and shuttles more phosphate ions into the production of ATP molecules.
Can Cancer Cause Low Phosphate Levels?
...