Phosphorus is the most abundant intracellular anion in the human body — it is the essential component of the high-energy phosphate bonds that store and transfer the metabolic energy in all cells. The high-energy phosphate bonds are the phosphoanhydride bonds in the ATP (adenosine triphosphate) and in the phosphocreatine (PCr), which store the energy that is released by the catabolic reactions (the oxidation of the glucose, of the fatty acids, and of the amino acids) and release it to power the endergonic reactions (the muscle contraction, the active transport, the biosynthesis, and the cell division). The phosphorus is also the essential component of the nucleic acids (DNA and RNA), of the phospholipids (which form the cell membranes and the mitochondrial membranes), of the phosphorylated signalling molecules (the second messengers cAMP, IP3, DAG, and the protein kinases that regulate the cell signalling pathways), and of the bone mineral (as the hydroxyapatite crystal, which is a complex of calcium and phosphate that provides the structural rigidity of the skeleton). Without adequate phosphorus, the ATP and the phosphocreatine pools are depleted, the cellular energy status collapses, and the muscle weakness, the rhabdomyolysis, the haemolytic anaemia, and the metabolic acidosis develop — the hallmark of the phosphorus deficiency. The typical dietary phosphorus intake is 1000-1500mg daily (from the dairy products, the meat, the poultry, the fish, the eggs, the legumes, and the fortified cereals), and the RDA is 700mg daily for adults — but the phosphorus deficiency is more common than generally recognised, particularly in people with the alcoholism, with the malnutrition, with the chronic antacid use (which impairs the phosphorus absorption by binding the phosphorus in the gut), and in people with the diabetic ketoacidosis (where the insulin deficiency drives the phosphorus into the cells and produces the severe hypophosphataemia).
Phosphorus and the ATP Synthesis
The ATP is the universal energy currency of the cell — it is the molecule that stores the energy that is released by the catabolic reactions and releases it to power the endergonic reactions. The ATP consists of the adenosine molecule (which is the nitrogenous base adenine bonded to the sugar ribose) and of the three phosphate groups (alpha, beta, gamma) that are linked by the phosphoanhydride bonds. The phosphocreatine (PCr) is the energy reservoir that is used to rapidly regenerate the ATP from the ADP when the ATP is depleted during the high-intensity muscle contraction — the creatine kinase enzyme transfers the phosphate from the PCr to the ADP, forming the ATP and the free creatine, and this reaction can be completed in milliseconds, allowing the rapid regeneration of the ATP for the muscle contraction. Both the ATP and the PCr require the phosphorus as their essential structural component — without adequate phosphorus, neither the ATP nor the PCr can be synthesised, and the cellular energy transfer system collapses. The phosphorus is also required for the function of the 2,3-bisphosphoglycerate (2,3-BPG) in the red blood cells — the 2,3-BPG binds to the haemoglobin and reduces its oxygen affinity, facilitating the oxygen release in the tissues.
The clinical importance of the phosphorus for the cellular energy metabolism is underscored by the observation that the severe hypophosphataemia (blood phosphorus below 0.5mg/dL) produces the respiratory failure, the cardiac failure, the rhabdomyolysis, the haemolytic anaemia, and the metabolic acidosis — which are the most life-threatening manifestations of the severe phosphorus deficiency and which are rapidly reversed by the phosphorus replacement. The rhabdomyolysis (the breakdown of the skeletal muscle) is one of the most dramatic manifestations of the severe hypophosphataemia — it is thought to be caused by the impaired ATP synthesis in the muscle cells, which leads to the failure of the sodium-potassium pump, the calcium accumulation in the muscle cells, and the activation of the proteolytic enzymes that digest the muscle protein.
Practical Application
For general phosphorus supplementation, the evidence-based approach is to ensure the adequate dietary phosphorus intake from the diverse food sources — the phosphorus is found in virtually all foods, and the dietary deficiency is rare in people who have access to adequate nutrition. The phosphorus is particularly abundant in the dairy products, the meat, the poultry, the fish, the eggs, the legumes, the nuts, and the seeds. The RDA of phosphorus is 700mg daily for adults, and the tolerable upper intake level is 4000mg daily for adults — above which the phosphorus can cause the gastrointestinal distress and can interfere with the calcium absorption (because the high phosphorus binds the calcium in the gut, forming the insoluble calcium phosphate). For comprehensive energy and bone health support, phosphorus pairs well with the calcium (which is the other component of the hydroxyapatite crystal and which works synergistically with phosphorus for the bone health), with the vitamin D (which promotes the intestinal absorption of both the calcium and the phosphorus), with the magnesium (which is a cofactor for many of the enzymes of the ATP metabolism and which is often deficient in people with the phosphorus deficiency), and with the vitamin K2 (which activates the osteocalcin and which is required for the incorporation of the calcium and the phosphorus into the bone matrix).
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