192 GROUP I AND II METALS IN BIOLOGICAL SYSTEMS
5.2 Homeostasis of Metals (and Some Nonmetals),
In a living system, homeostasis refers to a set of related and controlled steady
states in processes involving continuous changes in material, charge, and
energy fl ows into, out of, and within cells. Reagents must enter cells and prod-
ucts must leave. Inside cells a vast number of chemical reactions and transfor-
mations take place. The cell must maintain its structural organization, its
osmotic balance, and its material and electrical potential gradients. All bio-
chemically active inorganic species are involved in determining homeostasis;
in this chapter we will discuss the involvement of Na + , K + , Ca 2+ , Mg 2+ , and Zn 2+
with shorter discussions of P as PO 43 −, Cl − , and H +. Because all species noted
here are ions and interdependent upon one another for electroneutrality,
osmotic balance, and maintenance of concentration gradients, it will be diffi -
cult to separate discussions of each species.
5.2.1 Phosphorus as Phosphate,
In biological systems, phosphorus does not change oxidation state and is nor-
mally found as the phosphate ion, PO 43 −, often indicated, mostly by nonchem-
ists, as P i. In the human body, 80 – 85% of phosphorus is found in the skeleton
and 15 – 20% in organic compounds. The kidney plays a major role in phospho-
rus homeostasis. Interested readers will fi nd much more information at the
website http://www.wramc.amedd.army.mil/departments/medicine/Nephrology/
education/Lectures/CalciumAndPhosphorusHomeostasis_fi les/frame.htm .)
Phosphate ion concentration in blood serum is maintained within a narrow
range through a complex interplay between intestinal absorption, exchange
with intracellular and bone storage pools, and renal tubular reabsorption. The
kidney is a major regulator of P i homeostasis and can increase or decrease its
Pi reabsorptive capacity to accommodate P i need. The crucial regulated step
in P i homeostasis is the transport of P i across the renal (kidney) proximal
tubule. The type IIa sodium - dependent Na + /phosphate (P i ) cotransporter
(Npt2a), as regulated by hormonal [parathyroid hormone (PTH), for example]
and nonhormonal factors, plays a major role in P i homeostasis within renal
(kidney) tubules.^8
Phosphate ions are constituent parts of two universally found biopolymers,
DNA and RNA. Phosphate ion is found in membrane lipids (phospholipids)
and associated with the metabolism of many small molecules. The binding of
dioxygen by hemoglobin is regulated by local concentrations of H + (known as
the Bohr effect), CO 2 concentration, and organic phosphates such as diphos-
phoglycerate (DPG), whose structure is shown in Figure 5.1.^9
Phosphate ion is a major participant in the biological energy cycle through
the reactions of mono - , di - , and triphosphates, including one of the most
important of these reactions, producing adenosine diphosphate from adenos-
ine triphosphate (see structures in Section 2.3.1 , Table 2.2 ):