chemistry they will not be discussed further. The d-block metals have some biological
relevance, particularly Fe and Zn.
8.1.7.2 Metals in Biology and Medicine
Of the approximately 25 elements which are currently regarded as important if not
essential for life, four can be classified as bulk metal ions: Na, K, Mg, and Ca, and ten
as trace metal ions: Fe, Cu, Mn, Zn, Co, Mo, Cr, Sn, V and Ni. The nonmetallic ele-
ments are H, B, C, N, O, F, Si, P, S, Cl, Se and I. Over the past years, various evidence
has been put forth concerning the roles of Cd, As, Pb, and Al as potential trace elements.
These metals play a wide range of functional and structural roles within human
biochemistry.
The seven principal mineral macronutrient elements (Ca, Mg, Na, K, P, S, Cl) con-
stitute 70–80% of all the inorganic material in the body. Calcium is present in the body
in larger amounts than any other mineral element. A typical 70 kg adult male contains
1.5 kg of calcium; 98–99% of this is in the skeleton, where it is maintained as deposits
of calcium phosphates. Not surprisingly, calcium plays an important structural role
because of its central involvement in bone structure. Functionally, Ca^2 +is important to
electrical transmission within the brain and heart and to muscle contraction in both
skeletal and smooth muscle. Na+and K+ions are likewise crucial to the functioning of
excitable tissues such as neural, cardiac, and muscle tissues. Of the trace elements, the
important role of iron in the processes of cellular respiration, via hemoglobin, myoglo-
bin, and cytochromes, is well appreciated. Copper is present in two key enzymes of aer-
obic metabolism: cytochrome c oxidase, which is responsible for the major part of
oxygen consumed, and cytosolic superoxide dismutase, which catalytically scavenges
the toxic free radical superoxide ion generated during aerobic metabolism. Zinc is an
essential component of a number of enzymes present in animal tissues, including alco-
hol dehydrogenase, alkaline phosphatase, carbonic anhydrase, procarboxypeptidase,
and cytosolic superoxide dismutase. The enzyme pyruvate carboxylase, involved in
gluconeogenesis, contains tightly bound manganese.
Not only do metals play central roles in human biochemistry, but also various disease
states are recognized as arising from either deficiencies or excesses of various metal ions.
Individuals with cancer spreading into their bones may experience life-threatening
hypercalcemia from excessive blood concentrations of Ca^2 +. Elevated or reduced levels
of Na+(hypernatremia, hyponatremia) or K+(hyperkalemia, hypokalemia) can affect
electrical excitability in the brain or heart, leading to seizures or cardiac arrhythmias.
Iron deficiency leads to anemia; iron excess causes hemosiderosis, leading to liver and
pancreatic damage. Pronounced zinc deficiency in humans, resulting in dwarfism and
hypogonadism, has been described in geographical areas with zinc-deficient soil.
Excess copper produces a neurological disease known as Wilson’s disease, resulting in
disordered and abnormal body movement.
8.1.8 Endogenous Macromolecules as Drugs and Druggable TargetsThese seven groups of endogenous nonmessenger macromolecules offer a plethora of
leads as both drugs and druggable targets (see figure 8.5). In a somewhat arbitrary but
ENDOGENOUS MACROMOLECULES 481