Amino acids

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Amino acids
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Learning Objectives
Write the structural formulas of the 20 common
amino acids and selenocysteine, and identify by
name and three-letter abbreviation.
Describe the identification of the carbon atoms
in an amino acid.
Describe the R groups of amino acids in terms of
polar, nonpolar, aromatic, negatively and
positively charged.
Estimate the state of ionization of the carboxyl,
a-amino, and R group at a specific pH, given the
pKa.
Describe the effect of both bonded and non-bonded
groups on the pKa of ionizable functional groups.
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General structure of an amino acid
This structure is common to all but one of the
a-amino acids. Proline, a cyclic amino acid, is
the exception. The R group or side chain (red)
attached to the a carbon (blue) is different in
each amino acid.
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Structural features of the amino acids
The standard amino acids found in proteins are
a-amino acids.
They have a carboxyl group and an amino group
bonded to the same carbon (the a carbon).
They differ from each other in their side chains
or R groups
Except for glycine, the a-carbon is a chiral
center. The amino acids in proteins are L
stereoisomers.
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All molecules with a chiral center are optically
active. However, not all L amino acids are
levorotatory.
The L, D system is based upon the absolute
configuration of glyceraldehyde. (proposed by
Emil Fisher in 1891)
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Cahn-Ingold-Prelog or R,S system
In this system, all the amino acids from proteins
are (S)-amino acids (a-carbon), with the
exception of L-cysteine which is (R)-cysteine.
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Identification of carbons in amino acids
The additional carbons in an R group are commonly
designated b, g, d, e, and so forth, proceeding
out from the a carbon.
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The structural formulas show the state of
ionization that would predominate at pH 7.0.
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Absorbance of ultraviolet light by aromatic amino
acids
Comparison of the UV absorbance of tryptophan and
tyrosine (both at 10-3 M) at pH 6.0. Maximal
absorbance for both amino acids is around 280 nm.
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Reversible formation of a disulfide bond by the
oxidation of two molecules of cysteine.
Disulfide bonds between cys residues in proteins
stabilize the structures of many proteins.
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Non-standard amino acids
Both of these non-standard amino acids are found
in collagen, a fibrous protein of connective
tissue.
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Non-standard amino acids
Selenium functions as a necessary component of
enzymes involved in antioxidant protection
(glutathione peroxidase and thioredoxin
reductase) and thyroid hormone metabolism.
Selenium is incorporated as selenocysteine into a
wide range of selenoproteins. At least 30 have
been identified.
Selenocysteine
This amino acid is specifically coded for in the
mRNA of selenoproteins. A specific tRNA is
charged with selenocysteine and is incorporated
into the appropriate proteins during translation.
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Non-standard amino acids
Carboxylated glutamate
The blood clotting protein prothrombin contains a
number of g-carboxylglutamate residues in its
amino-terminal region introduced by an enzyme
that requires vitamin K. These carboxyl groups
bind Ca2, required to initiate the clotting
mechanism.
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Some methylated amino acids
Monomethyl- and dimethyllysine residues occur in
some muscle proteins and cytochrome c. Calmodulin
of most organisms contains one trimethyllysine at
a specific position. When the carboxyl group of
glutamate is methylated, the negative charge is
removed.
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Amino acids can act as acids and bases
When an amino acid is dissolved in water, it
exists in solution as the dipolar ion, or
zwitterion. A zwitterion can act as either an
acid or a base.
Substances having this dual nature are amphoteric
and are often called ampholytes.
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Amino acids have characteristic titration curves
pI isoelectricpoint
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Selenium
Deficiencies selenium
Characteristic signs of selenium deficiency have
not been described in humans, but low selenium
intake is a factor in the etiology of Keshan
disease that occurs in a selenium-deficient
region of China.
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Food sources selenium
Seafood (salmon, halibut, shrimp) and meat are
good sources of selenium. Brazil nuts can have
high levels of selenium (depends upon soil
levels). Most fruits and vegetables are low in
selenium.
Livestock (chicken, turkey, beef, pigs) may have
selenium supplements in feed. Selenium levels in
chicken and turkey appear higher than expected.
(Dog food may or may not have selenium additives).
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Methionine is an essential amino acid.
Seleno-methionine is readily absorbed from
dietary sources, especially plants, which take up
selenium although they do not appear to require
this element. Seleno-methionine competes with
methionine in normal protein synthesis. (This may
contribute to the toxic effects seen in waterfowl
that ingest plants in high-selenium wetlands).
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2 GSH R-O-O-H GS-SG H2O R-OH
Glutathionine peroxidase removes toxic peroxides
formed in the normal course of growth and
metabolism.
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Role of NADPH and glutathionine peroxidase in
protecting cells against reactive oxygen species
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Thioredoxin reductase catalyzes the NADPH
dependent reduction of thioredoxin.
-selenocysteine-Se-S-cysteine-
About 60 of Se in plasma is incorporated into
selenoprotein P which contains 10 Se atoms per
molecule as selenocysteine this protein may
facilitate whole body transport of selenium.
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iodothyronine deiodinase enzymes catalyze the
5-mono-deiodination of the prohormone thyroxine
(T4) to the active thyroid hormone
3,3,5-triiodothyronine (T3).
Sperm capsule selenoprotein is localized in the
mid-piece portion of the spermatozoa where it
stabilizes the integrity of the sperm flagella.
Selenium intake effects the concentration of
selenoprotein W which is reported to be necessary
for muscle contraction.
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Selenium content in grain forage in North America
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The hazards of modern living Increasing levels
of oxidants and toxic/unnatural substances in the
environment ozone, UV light, air pollutants,
water pollutants, food preservatives, pesticides,
herbicides These conditions put chemical stress
on the detoxification mechanism (in the liver)
and repair mechanism of the body (i.e. DNA
repair).
Supplement with antioxidants (?)
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In the Keshan region of China, a serious heart
disease (cardiomyopathy) was found to be
associated with a selenium deficiency in the
diet. This region of China has very poor soil
levels of selenium.
However, the disease was seasonal. This
suggested that other, unknown factors were
operative. Coxsackievirus isolated from patients
with Keshans disease. In selenium deficient
mice, this virus mutates to a much more virulent
form and causes an inflammation of the heart
muscle (myocarditis). This change in the virus
occurs only in selenium-deficient mice.
Glutathione peroxidase knockout mice showed an
increased susceptibility to virial induced
myocarditis.
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Current theory oxidative stress induces virial
changes to more virulent forms.
Declining selenium levels in HIV-infected
patients are sensitive markers of disease
progression and severity. The activity of the
virus (and the human immune system) is affected
by selenium nutritional status. The HIV genome
codes for selenoproteins.
The Ebola virus breakouts of this virus occur in
areas where soil selenium levels are low.