tannins:
a mixture of naturally occuring polyphenols (usually bioflavonoids
and esters of gallic acid) and their products of autooxidation. Oxidized
tannins readily form imines with primary amines, which develope a brown
or tan color. Polyphenols are quite active as reductants and useful as
antioxidant additives. Many impart sweet flavors and pleasant aromas to
foods. Oxidized tannins on the other hand are bitter tasting, astringent,
and possess antibacterial properties.
target:
the sensor or receptor of an action; the molecular types thought to
be altered by the administration of a nutrient, toxin, or medicinal agent.
In the context of bio-oxidative medicine, the targets are expected to be
any molecular type vulnerable to oxidation. Candidates for consideration
are molecules baring reactive groups which are capable of donating
electrons or hydrogen atoms such as thiols, amines, phenols, enediols,
hydroquinones, dihydroflavins, etc.
tautomer:
an isomer which differs only in the location of a hydrogen atom.
Tautomers are noted for their ability to switch from one form to the
other with little energy change between the two forms. For certain
tautomers one form is more readily oxidizable than the other. Also
certain molecules upon acceptance of hydrogen will subsequently
tautomerize to a form different from the immediate product.
termination:
any chemical reaction which eliminates or deactivates free
radicals so as to halt their activity. This can be accomplished by
coupling, trapping, single electron reduction of the free radical, or
single electron oxidation of the free radical.
terrain:
the environment in which a living thing attempts to survive.
A living does not thrive nor compete effectively for nutrients and
resources unless situated under conditions well suited to its unique
needs. This principle is well recognized in botany, but also applies
to infectious disease. Pathogens will only succeed to infect a host which
favors their survival by providing the particular metabolic conditions
required for them to function optimally. For example: many urinary
pathogens cannot infect the urinary tract if the urine is acidified but
will readily infect if the urine is alkaline; Candida albicans thrives
best under conditions of high carbohydrate availability; most bacteria
cannot multiply except within a pro-reductant medium.
tetrahydrofolate (THF or FH4):
the metabolically activated form of folic acid.
Folates are not useful as carriers of methyl, methylene, or formyl groups
unless and until they are converted by folate reductases to THF. Thus all
synthetic functions served by THF are indirectly dependent upon an ample
supply of reducing equivalents supplied by NADPH.
thiobarbituric acid reactive substances (TBARS):
a test commonly performed on lipid samples from food, from living
things, or from other sources to detect levels of malondialdehyde
(MDA) and other similar molecules. TBA reacts with MDA to form
a stable adduct which is readily quantifiable. Since MDA is a major
breakdown product of lipid peroxidation, the TBARS test is useful
to guage the extent of lipid peroxidation which has taken place.
thioctic acid:
alpha lipoic acid.
thiohemiacetal (R-S-HCOH-R'):
the product of the addition of a thiol to an aldehyde.
The reaction is reversible and accounts for the temporary
inactivation of thiols in the presence of toxic levels
of aldehydes. Certain enzymes such as glyoxylase utilize
thiohemiacetal formation to trap alphaketoaldehydes and
subsequently to convert them to alphahydroxycarboxylic acids.
thiolate anion (RS-):
the conjugate base of the thiol group (RSH). RS- is
especially vulnerable to oxidation being a relatively strong reductant.
Oxidation of RS- produces the thyil radical (RS*). RS- binds as a ligand
to most heavy or transition metal cations. When stereochemically permitted
RS- readily exchanges with another sulfide within a disulfide.
thiol disulfide exchange (TDE):
a reaction between a thiolate anion (RS-)
and a disulfide (R'SSR'') in which the approaching thiolate anion changes
places with one or the other sulfide of the couple. This is a nucleophilic
substitution reaction. (RS- + R'SSR''---> RSSR''+ R'S-). TDE is important
to the mechanism of action of many enzymes and cofactors including
coenzyme A and glutathione. TDE alters the structure and activity of
numerous proteins.
thiol group (-SH):
a sulfur atom covalently bond to the rest of the molecule
on one side and a hydrogen atom on the other. Thiols (RSH) are oxidizable
to the thyil radical (RS*). Under alkaline conditions (pH over 8.0) a
thiol will ionize to its conjugate base the thiolate anion (RS-).
RS- is significantly more vulnerable to oxidation than is RSH.
thioredoxin (Trx):
an ubiquitous protein possessing two redox active cysteine
residues functioning as a hydrogen carrier or shuttle. In its reduced
state the two thiol groups of the cysteine residues of Trx are closely
situated (Trx-SH HS-). When Trx delivers its two thiol hydrogens to
another acceptor, the sulfur atoms couple to form a disulfide (Trx-SS-).
The flavoprotein thioredoxin reductase (TR) recharges the disulfide form
donating two new hydrogen atoms thus restoring the original dithiol form.
Thioredoxin activates various reductases and transcription proteins.
Its role in the activation of ribonucleoside reductase (RR) makes Trx and
other activators of RR (all thiol compounds) essential to DNA synthesis.
Pro-oxidant conditions have been shown to inhibit DNA synthesis by
depletion of hydrogen from this family of RR activators.
thioredoxin reductase (TR):
an oxidoreductase activated by NADPH and
utilizing FAD in its active center which serves to hydrogenate
thioredoxin.
thiyl radical (RS*):
the molecular species produced by the abstraction of
one atom of hydrogen from a thiol group (RSH) or by the removal of one
electron from a thiolate anion (RS-). Whereas thiyl radicals can add to
the pi bonds of other molecules, they more readily tend to couple so as
to produce disulfides (RSSR').
thyroxine (T4):
the hormone produced by the thyroid gland which contains
four iodine molecules. T4 can be deiodinated enzymatically to T3. Both
stimulate various metabolic functions including oxygen utilization and
heat production. Thyroid hormones induce enhanced activity of glycerol-3-
phosphate dehydrogenase.
thymidylate synthetase:
the enzyme which catalyses the methylation of deoxy-
uracilmonophosphate (dUMP) to produce deoxythymidinemonophosphate (dTMP).
dTMP is an essential precursor to DNA synthesis. The process utilizes
N5,N10-methylene-tetrahydrofolate to supply the methyl group thus
producing dihydrofolate (FH2). FH2 must be reduced to FH4 by NADPH
(catalyzed by dihydrofolate reductase) each time this process is served.
Thus DNA synthesis is dependent upon an adequate supply of NADPH.
tocopherol (vit E):
a monophenolic compound with a long turpenoid lipophilic
side chain useful as a reductive antioxidant in food, in vivo, and in
research.
transaminase:
an enzyme which transfers amino groups from a primary amine
to another molecule which has a carbonyl group. In the process the donor
amine becomes a carbonyl compound and the receiving carbonyl compound
becomes an amine. Transaminases utilize pyridoxal phosphate as the
prosthetic group. The reaction mechanism involves the reversible formation
and tautomerization of imines (Schiff's bases).
transcription factor:
any component involved in the process of physiologic
induction which migrates from a trigger or receptor in the membrane or
cytosol to the nucleus where it activates the production of specific mRNA.
Many transcription factors are peptides which contain cysteine residues
and can be reversibly inactivated by oxidation.
trapping:
the binding of a free radical to another molecule, usually a pi
bond, in such a fashion that the reaction cannot continue to propagate.
trigger:
a physiologic receptor or sensor which can be activated by various
stimuli and initiate a response mechanism. Certain intermediates in the
chain of events pertaining to physiologic trigger activation, including
sometimes the triggers themselves, can be modulated by reductants and
oxidants. This provides a mechanism for oxidants even at low dosage to
bring about major alterations in the physiologic responses of an organism.
trihydroxyphenylalanine quinone (TPQ):
TOPA quinone; 2-oxo-4-hydroxy-5-oxo-phenylalanine;
a benzoquinone amino acid. TPQ is part of the redox active
center of diamine oxidase and certain other oxidoreductases.
The protein as first synthesized in the ribosome contains
tyrosine, which is subsequently oxidatively modified to a
2,5-quinone.
triplet:
a term derived from spectroscopy which displays a three part signal
produced by diradicals; the diradical form of a molecule (usually an
energized pi bond) which has its two electrons occupying higher energy
molecular orbitals in which the two electrons are no longer spin paired.
Diatomic oxygen is peculiar in that its lowest energy configuration is
not a singlet like "normal" double bonds. It is able to form a special low
energy triplet state below its "normal" singlet state. Being a diradical,
ground state diatomic oxygen is paramagnetic and appears as a triplet
spectrographically.
triquinoyl:
a ringed molecule composed of 6 conjugated carbonyl groups.
Triquinoyl redox cycles under biologic conditions and
therefore has been used as an oxidative catalyst.
tryptophan tryptophylquinone (TTQ):
part of the redox active center for the bacterial enzyme
methylamine dehydrogenase. It is composed of two tryptophan
residues, which are covalently bound, one of which is
oxidatively modified to a 6,7-quinone.
tumor necrosis factor (TNF):
a cytokine with antineoplastic effects.
turpenes:
organic compounds produced by polymerization of isoprene groups.
See isoprenoids.
tyrosine protein kinase (TPK):
a phophorylase which converts the phenolic
hydroxyl groups of certain tyrosine residues in a target protein to
ortho-phosphotyrosine. This is part of a physiologic intracellular
signal or activation mechanism. Overexpression of TPK's is a feature
of viral infection and of growing tumors. Many oncogenes code for the
synthesis of TPK's.
