Similarly, high levels of O 3 can induce peroxidation of the polyunsaturated
fatty acids in the lipid portion of membranes, resulting in disruption of
membrane structure.
6
4.4.2 CHEMICAL COMBINATION WITH A CELL CONSTITUENT
A pollutant may combine with a cell constituent, forming a complex and
disrupting cellular metabolism. For example, CO is widely known for its ability
to bind to hemoglobin (Hb). After its inhalation and diffusion into the blood,
CO readily reacts with Hb to form carboxyhemoglobin (COHb):
CO þ Hb ! COHb
ð4:1Þ
The presence of a large amount of COHb in the blood disrupts the vital
system for exchange of CO 2 and O 2 between the blood and the lungs and other
body tissues. Interference with the functioning of hemoglobin by COHb
accumulation is detrimental to health and can lead to death.
A number of toxicants or their metabolites are capable of binding to DNA
to form DNA adducts. Formation of such adducts results in structural changes
in DNA, leading to carcinogenesis. For instance, benzo[a]pyrene, one of the
many polycyclic aromatic hydrocarbons (PAHs), may be converted to its
epoxide form in the body. The resultant epoxide can in turn react with guanine
on a DNA molecule to form a guanine adduct. Another example is found with
alkylating agents. These chemicals are metabolized to reactive alkyl radicals,
which can also induce adduct formation. These will be discussed in more detail
in Chapter 16.
Certain metallic cations can interact with the anionic phosphate groups of
polynucleotides. They can also bind to polynucleotides at various specific
molecular sites, particularly purines and thymine. Such metallic cations can,
therefore, inhibit DNA replication and RNA synthesis and cause nucleotide
mispairing in polynucleotides. An anatomical feature of chronic intoxication of
Pb in humans and in various animals is the presence of characteristic
intranuclear inclusions in proximal tubular epithelial cells in the kidneys.
These inclusions appear to be formed from Pb and soluble proteins.
7 By tying
up cellular proteins, Pb can depress or destroy their function.
4.4.3 EFFECT ON ENZYMES
The most distinctive feature of reactions that occur in living cells is the
participation of enzymes as biological catalysts. Almost all enzymes are
proteins with a globular structure, and many of them carry out their catalytic
function by relying solely on their structure. Many others require nonprotein
components, called cofactors. Cofactors may be metal ions or alternatively they
may be organic molecules, called coenzymes. Metal ions capable of acting as
cofactors include K
þ , Na
þ , Cu
2þ , Fe
2þ or Fe
3þ , Mg
2þ , Mn
2þ , Ca
2þ
, and Zn
2þ
ions (Table 4.2). Examples of coenzymes that serve as transient carriers of
Toxic Action of Pollutants
53
[16:54 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-004.3d]
Ref: 4365 MING-HO YU Chap-004 Page: 53 45-64
fatty acids in the lipid portion of membranes, resulting in disruption of
membrane structure.
6
4.4.2 CHEMICAL COMBINATION WITH A CELL CONSTITUENT
A pollutant may combine with a cell constituent, forming a complex and
disrupting cellular metabolism. For example, CO is widely known for its ability
to bind to hemoglobin (Hb). After its inhalation and diffusion into the blood,
CO readily reacts with Hb to form carboxyhemoglobin (COHb):
CO þ Hb ! COHb
ð4:1Þ
The presence of a large amount of COHb in the blood disrupts the vital
system for exchange of CO 2 and O 2 between the blood and the lungs and other
body tissues. Interference with the functioning of hemoglobin by COHb
accumulation is detrimental to health and can lead to death.
A number of toxicants or their metabolites are capable of binding to DNA
to form DNA adducts. Formation of such adducts results in structural changes
in DNA, leading to carcinogenesis. For instance, benzo[a]pyrene, one of the
many polycyclic aromatic hydrocarbons (PAHs), may be converted to its
epoxide form in the body. The resultant epoxide can in turn react with guanine
on a DNA molecule to form a guanine adduct. Another example is found with
alkylating agents. These chemicals are metabolized to reactive alkyl radicals,
which can also induce adduct formation. These will be discussed in more detail
in Chapter 16.
Certain metallic cations can interact with the anionic phosphate groups of
polynucleotides. They can also bind to polynucleotides at various specific
molecular sites, particularly purines and thymine. Such metallic cations can,
therefore, inhibit DNA replication and RNA synthesis and cause nucleotide
mispairing in polynucleotides. An anatomical feature of chronic intoxication of
Pb in humans and in various animals is the presence of characteristic
intranuclear inclusions in proximal tubular epithelial cells in the kidneys.
These inclusions appear to be formed from Pb and soluble proteins.
7 By tying
up cellular proteins, Pb can depress or destroy their function.
4.4.3 EFFECT ON ENZYMES
The most distinctive feature of reactions that occur in living cells is the
participation of enzymes as biological catalysts. Almost all enzymes are
proteins with a globular structure, and many of them carry out their catalytic
function by relying solely on their structure. Many others require nonprotein
components, called cofactors. Cofactors may be metal ions or alternatively they
may be organic molecules, called coenzymes. Metal ions capable of acting as
cofactors include K
þ , Na
þ , Cu
2þ , Fe
2þ or Fe
3þ , Mg
2þ , Mn
2þ , Ca
2þ
, and Zn
2þ
ions (Table 4.2). Examples of coenzymes that serve as transient carriers of
Toxic Action of Pollutants
53
[16:54 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-004.3d]
Ref: 4365 MING-HO YU Chap-004 Page: 53 45-64