Fe, PO4, Ca2+

Brody T. Iron. In;Brody T, ed. Nutritional biochemistry. 2nd ed. San Diego. Academic Press1999;739-751 A striking feature of iron is that it occuires as free iron in concentrations that are extremely low in the body. This is in contrast to free calcium ions, which occur at about 2 mM in the plasma, and free potassium ions, which are about 140 mM in the cell. There are two reasons that nearly all of the iron in the body is protein bound, rather than free. The first is that iron (ferric iron) us not soluble in water. Another reason is that free iron (ferrous iron) can be toxic to the cell. The complexation of iron with proteins may prevent its participation in generation of hydroxyl radicals. Dietary iron consists of iron bound to the heme prosthetic group of heme-iron proteins The heme iron proteins include hemoglobin, myoglobin, the cytochromes, catalase, peroxidase, endoperoxide synthase, and myeloperoxidase. The iron in nonheme enzymes is tightly bound to the sulfur atoms of cysteine residues. Hence, these enzymes are called "iron-sulfur proteins". The nonheme iron proteins include ribonucleotide reductase, etc. Iron in the human body Hemoglobin contains about 60% of the body's iron. Myoglobin represents under 4% of the body's iron. Ferritin represents between 5 and 30% of the body's iron. Absorption of iron Phytic acid is a major inhibitor of iron absorption in plant foods. Phytate also binds calcium and zinc ions, limiting their availability as well. About half of the phosphate in grain may be in the form of phytate. The outer layers of the seeds of plants such as wheat, rice, maize, millet, barley, and oats are covered with a husk containing indigestible fiber. The outer layers of the seeds also contain most of the phytate of the seed. Iron exists in two forms; in the reduced form (ferrous rion, Fe 2+) and the oxidized form (ferric iron, Fe3+). Ferrous sulfate is a form of iron that is most readily absorbed by the gut, but when added to dry cereals it can promote their spoilage and rancidity. For this reason, dry cereals are fortified with elemental iron particle, ferric pyrophosphate, or ferrous fumarate. (Davidsson et al, 1997) Davidsson L, Galan P, Cherouvrier F, Kastenmayer P, Juillerat MA, Hercberg S, Hurrell RF. Bioavailability in infants of iron from infant cereals: effect of dephytinization. Am J Clin Nutr. 1997 Apr;65(4):916-20. Phosphate The predominant form at neutral pH is HPO4  2-. The fully protonated form, which is the predominant form in an environment of low pH, is phosphoric acid (H2PO4). Free phosphate is called inorganic phosphate. Is is abbreviated by Pi. The phosphate covalently bound to sugar, proteins, and other componets of the cell is called organic phosphate. The cleavage of the phosphate group from organic phosphate results in an increase in entropy, and therefore in the liberaton of energy. ATP-dependent enzyme have the property that they can capture this release of energy, and couple it with an otherwise energetically unfavorable reaciton, such as the formation of a peptide bond. Phosphate and energy storage and transfer The phosphate group most commonly associated with temporary energy storage, and energy transfer, is the terminal phosphate group of ATP. It is thought that about 25% of the ATP synthesized per day is used by the sodium pump (Na, K-ATPase). The amount of energy discharged with the hydrolysis of various organic phosphate bonds varies from a low of 13.8 kJ/mol for glucose-6-phosphate to a high of 61.9 kJ/mol for phosphoenolpyrovate (PEP). The amount of energy released with the hydrolysis of ATP to ADP + Pi is 31.8 kJ/mol (Bridger and Henderson, 1983). Bridger WA, Henderson JE, (1983). "Cell ATP," pp. 9-19. Wiley, New York. The relative large amount of energy released with the hydrolysis of moledules such as ATP and PEP is due to the seperation of the negative charges as the Pi is released from the parent molecule. Hydrolysis of ATP relieves the internal strain cuased by the negative charges of adjacent phosphate groups. Cleavage of phosphate from goucose-6-phosphate does not result in any such charge separaton. Phosphate in nucleic acids A universal function of phosphate is as a component of DNA and RNA. The molecular glue in these polymers is the phosphate group. The phosphate group links two adjacent nucleotides. The phosphate group remains negatively charged in this linkage. The negative charge stabilizes the polymer against spontaneous, nonenzymatic hydrolysis. The advantage of the phosphate group as a linking molecule is that it can bind to two organic molecules, via their hydroxyl groups, and yet remain negatively charged (Westheimer, 1987). Westheimer FH. Why nature chose phosphates. Science. 1987 Mar 6;235(4793):1173-8.  Accidental hydrolysis of a DNA polymer may involve the attack of a free hydroxyl anion. The negative charge of the phosphate linkage of DNA repels such an attack. The sulfate group holding DNA or RNA is relatively unstable, It is able to link two organic molecules, but it lacks a negative charge in this linkage. It is susceptible to attack by a hydroxyl group. Phosphate groups prevent phosphorylated compounds from leaking out In addition to ist function in bone, energy transfer, and nucleic acids, phosphate serves to prevent the leakage of biochemicals from the cell. The phosphate groups of nucleotides, intermediates of glycolysis, and vitamin B6 greatly impair the passage of these molecules through membranes. The phosphate group increases the hydrophilicity of the compound, reducing its tendency to enter into the lipophilic environment of the membrane's interior. Other roles of phosphate groups occur in phopholipids and in the covalent modification of proteins. Brody T. Phosphate. In;Brody T, ed. Nutritional biochemistry. 2nd ed. San Diego. Academic Press1999;762-765   Calcium A dietary deficiency in calcium or phosphate is rare. The optimal amounts of calcium and phosphate are not clear and remain a subject of some controversy. Increasing dietary protein can induce excessive loss of calcium in the urine and a negative calcium balance. The mechanism is not clear. Elevated levels of plasma sulfate can form a complex with calcium. The complex passes into to renal tubule, where i is poorly reabsorbed, resulting in its excretion in the urine. Brody T. Calcium. In;Brody T, ed. Nutritional biochemistry. 2nd ed. San Diego. Academic Press1999;772.