Biomedical Engineering Reference
In-Depth Information
related to the extended family of structurally l exible calmodulins, which are calcium-binding
proteins that can bind to and regulate a multitude of different protein targets, thereby affecting
many different cellular functions.
10.6.3 I
RON
AND
C
OBALT
Iron plays the leading role in all biological processes wherein oxygen turnover takes place. Iron(II)
coordinates to a certain type of porphyrin and forms a complex labeled heme (Figure 10.8).
Vertebrates utilize two such heme proteins for reversible O
2
transport and storage: hemoglobin in
red blood cells and myoglobin in muscle tissue. Anemia results from insufi cient dioxygen supply
usually due to a low hemoglobin blood level.
A signii cant heme enzyme is cytochrome P-450, a dioxygen activating metalloporphyrin that
catalyzes a series of important biological oxidation processes. Enzymatic monooxygenation reac-
tions, e.g., the conversion of vitamin-D or transformation of drugs like morphine are indicative of
such processes. Unwanted transformations like epoxidation of benzene to produce carcinogenic
derivatives or oxidation of nitrosamines to form reactive radicals are examples of a toxicological
function of cytochrome P-450.
For every 30 seconds, a child in Africa dies from malaria and the commonly used antima-
larial therapy has become increasingly ineffective due to chloroquine resistance. However, a new
series of drugs based on tervalent metal ion coordination compounds, like the ethylenediamine-
bis[propylbenzylimino]Fe(III) complex, exhibit highly selective activity, ironically, particularly
against chloroquine-resistant parasites. Heme, released from hemoglobin in the parasite, is very
toxic to eukaryotic cells due to lysing of the membranes. In order to prevent this destructive action,
the parasite polymerizes heme, but the aforementioned imino complexes inhibit this protective pro-
cess thereby destroying the parasite.
Transport and storage of iron have been studied assiduously. As Fe(II) easily becomes oxidized
to Fe(III) the products formed are in general highly insoluble at pH 7, unless Fe(III) becomes
sequestered to some chelate like the siderophores (Section 10.5.4; cf. Figure 10.4C). The salmonella
FIGURE 10.8
Heme. The heme prosthetic group consists of an iron(II) ion (magenta) complexed in a square
planar geometry to four pyrrole nitrogen atoms (blue) of a substituted porphyrin ligand.
