Microbiology and Immunology

(Axel Boer) #1
Amino acid chemistry WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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ities, which he argued should be centered on basic research
rather than regulation; and finally his belief that the large pub-
lic expenditures incurred by the regulatory process hurt
American economic competitiveness.
Ames and his colleague Gold have also argued that the
use of bioassays (animal tests) of chemicals to predict their
carcinogenic potential in humans should be abandoned. In a
typical bioassay, rats are given a maximum tolerated dosage
(MTD) of a particular chemical daily for a period of time
(such as a year). The maximum tolerated dosage is as much as
the animal can be given without immediately becoming ill or
dying. At the end of the time period, the number of animals
that have developed cancers is tabulated as an indicator of the
cancer causing potential of the chemical being tested. Ames
suggested that it is often the large dosage itself, rather than the
nature of the particular chemical that induces the rat cancers.
He argued that, since humans are not normally exposed to
such large doses, the assays were not valid for predicting
human cancers.
Ames’s arguments have some support both within and
outside scientific communities. However, he also has numer-
ous critics. Those taking issue with his positions have noted
that pollution control, for example, involves far more than just
carcinogenicity. These critics suggest that Ames has not
offered a substitute for animal assays (the Ames test has not
proved to be such a substitute), and that neither he nor they
have a good idea of what goes on at low dosages. Some argue
that Ames has an over-simplified view of the regulatory
process, which is based on a consideration of animal assays
but also on other factors. It has also been argued that the dis-
covery that many naturally occurring chemicals have a high
mutagenic rate (just as synthetic chemicals) should not lead to
the conclusion that synthetic chemicals pose less risk than was
previously supposed. Such an assumption places too much
emphasis on mutagenic rate as a sole indicator of carcino-
genicity, ignoring the complex, multi-stage developmental
process of the disease.
Yet the disagreements between Ames and his critics are
based on several points of commonality—that cancer is a
complex multi-stage process that is not fully understood; that
there is no perfect test or group of tests that can fully predict
the potential carcinogenicity of many substances in humans;
and that public regulatory and environmental policies must be
made and carried out in spite of this deficiency of knowledge.
As for Ames, he has described his public-policy activism as a
hobby, and he has noted that his recent scientific work
includes studies in the biochemistry of aging.
Elected to the National Academy of Sciences in 1972,
Ames has received many awards, including the Eli Lilly
Award of the American Chemical Society (1964), the Mott
Prize of the General Motors Cancer Research Foundation
(1983), and the Gold Medal of the American Institute of
Chemists (1991). He is the author or coauthor of more than
250 scientific articles.

See also Chemical mutagenesis; Molecular biology and
molecular genetics

AAmino acid chemistryMINO ACID CHEMISTRY

Amino acids are the building blocks of proteins and serve
many other functions in living organisms. The prime function
of DNAis to carry the information needed to direct the proper
sequential insertion of amino acids into protein chain during
protein synthesis(translation).
An amino acid is a molecule that contains a terminal
acidic carboxyl group (COOH) and a terminal basic amino
group (NH 2 ). The approximately 20 amino acids (plus a few
derivatives) that have been identified as protein constituents
are alpha-amino acids in which the -NH 2 group is attached to
the alpha-carbon next to the -COOH group. Thus, their basic
structure is NH 2 CHRCOOH, where R is a side chain. This side
chain, which uniquely characterizes each alpha-amino acid,
determines the molecules overall size, shape, chemical reac-
tivity, and charge. There are hundreds of alpha-amino acids,
both natural and synthetic.
The amino acids that receive the most attention are the
alpha-amino acids that genes are codes for, and that are used
to construct proteins. These amino acids include glycine
NH 2 CH 2 COOH, alanine CH 3 CH (NH 2 ) COOH, valine
(CH 3 )2CHCH (NH 2 )COOH, leucine (CH 3 ) 2 CHCH 2 CH(NH 2 )
COOH, isoleucine CH 3 CH 2 CH(CH 3 )CH(NH 2 )COOH, methi-
onine CH 3 SCH 2 CH 2 CH(NH 2 )COOH, phenylalanine C 6 H 5 CH 2
CH(CH 2 )COOH, proline C 4 H 8 NCOOH, serine HOCH 2 CH
(NH 2 )COOH, threonine CH 3 CH(OH)CH(NH 2 )COOH, cys-
teine HSCH 2 CH(NH 2 )COOH, asparagine, glutamine H 2 NC
(O)(CH 2 )2CH(NH 2 )COOH, tyrosine C 6 H 4 OHCH 2 CHNH 2
COOH, tryptophan C 8 H 6 NCH 2 CHNH 2 COOH, aspartate
COOHCH 2 CH(NH 2 )COOH, glutamate COOH(CH 2 )2CH
(NH 2 )COOH, histidine HOOCCH(NH 2 )CH 2 C 3 H 3 H 2 , lysine
NH 2 (CH 2 ) 4 CH(NH 2 )COOH, and arginine (NH 2 )C(NH)
HNCH 2 CH 2 CH 2 CH(NH 2 )COOH.
Proteins are one of the most common types of mole-
cules in living matter. There are countless members of this
class of molecules. They have many functions from compos-
ing cell structure to enabling cell-to-cell communication. One
thing that all proteins have in common is that they are com-
posed of amino acids.
Proteins consist of long chains of amino acids con-
nected by peptide linkages (-CO.NH-). A protein’s primary
structure refers to the sequence of amino acids in the mole-
cule. The protein’s secondary structure is the fixed arrange-
ment of amino acids that results from interactions of amide
linkages that are close to each other in the protein chain. The
secondary structure is strongly influenced by the nature of the
side chains, which tend to force the protein molecule into spe-
cific twists and kinks. Side chains also contribute to the pro-
tein’s tertiary structure, i.e., the way the protein chain is
twisted and folded. The twists and folds in the protein chain
result from the attractive forces between amino acid side
chains that are widely separated from each other within the
chain. Some proteins are composed of two of more chains of
amino acids. In these cases, each chain is referred to as a sub-
unit. The subunits can be structurally the same, but in many
cases differ. The protein’s quaternary structure refers to the
spatial arrangement of the subunits of the protein, and

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