radical (R-X):
a part of a molecule that protrudes outward as a ray or limb.
Bound radicals are attached by covalent bonds or other chemical bonding
mechanisms. Free radicals are considered to be broken off fragments or
pieces of a molecule. The term free radical as conventionally used is
reserved more specifically only for molecular species that possess an
unpaired electron.
reaction mechanism:
the exact order of events that take place in a chemical
change, including intermediary species involved, the spacial relationships
of the atoms involved, the energy conversions, the characteristics of the
molecular orbitals and bonds involved, and the means by which the end
products are formed. Knowledge of reaction mechanisms are important to
understanding how exactly to intervene if a change in the final results
is desired.
reactivation:
altering the conditions within or about an inhibited enzyme
so as to enable it to function again. Examples follow. Intestinal
digestive enzymes are nonfunctional in mildly acidic solution, but will
resume function when in a mildly alkaline solution. Any reductase which
utilizes electrons from NADPH will abruptly fail to reduce its substrate
once the supply of NADPH is exhausted. It will resume reductase activity
promptly upon reintroduction of NADPH. Enzymes utilizing thiol groups can
be fixed in an inactive state by the mercury II cation (Hg++). Its
function can often be restored by the introduction of other thiol
compounds which compete for Hg++ binding, thereby taking Hg++ out of the
enzyme. Similarly enzymes and transcription factors which require the
thiol group to function can be reversibly inhibited by oxidation which
converts the thiol to a disulfide. Reduction of the disulfide back to
the thiol restores function.
reagent:
a contraction of the words reactive and agent; a reactant in pure form;
substance which reacts in a predictable manner.
receptor:
the molecular target of a medicine or poison; the site at which
a substance entering a living thing reacts; the point at which
a physiologic response from a substance occurs. In bio-oxidative
medicine the receptors are: 1) various reductants, which are already
present in abundance in living things; and 2) certain oxidant
sensors at the cellular level.
redosis:
the condition of abnormal or excessive levels of reductants in a
biologic fluid. Redosis can result from a deficiency of oxidant
supply, from any deactivation of oxidants, from the introduction
of excessive doses of reductants, or from the overactive production
of reductants. The extent of redosis is quantifiable by an electrode
redox:
a contraction of the words reduction and oxidation; pertaining to
chemical reactions which involve the transfer of electrons or hydrogen
atoms.
redox active center:
that part of an oxidoreductase which accepts reducing
equivalents only to donate them again to another substrate. Numerous types
of redox active centers are known to exist in all living things. These
involve reactive groups which can themselves readily be reduced and then
oxidized again and again. Examples are: iron, iron-sulfur compounds,
copper, manganese, molybdenum, thiols, selenols, quinones, phenols,
enediols, pyridiniums, flavins, pterins, phenazines, porphins.
redox couple:
any two reactants which are able to engage in a transfer of
electrons or hydrogen atoms. The donor is the reductant, and the acceptor
is the oxidant. Considered together they form the redox active couple.
redox cycling:
the process of reversible and repeated reduction and oxidation.
The active centers of all oxidoreductases redox cycle every time they act.
Proteins which contain exposed thiol groups (the side chains of cysteine
residues) are said to redox cycle as they alterate between dithiol
(RSH HSR') and disulfide (RSSR') states. Ferric cations, cupric cations,
pyridiniums, and quinones in the free dissociated state can accept
electrons from various reductants and reversibly pass them on to oxygen.
They are said to redox cycle as they perform this process which can go
on indefinitely.
redox potential:
a measure of the energy change involved in an oxidation
reduction; the tendency of an electron transfer to take place between
components of a proposed redox couple; the predicted voltage of a redox
couple as calculated from available information using the Nernst equation;
the measured voltage of a redox couple using separated half cells,
a salt bridge, conductive wires, and a volt meter.
redox regulation:
the tendency of living things to compensate for changes
in the relative availability or activity of physiologic reductants and
oxidants; the modulation of the activity of an enzyme or physiologic
signal mechanism by changes in its status whether oxidized or reduced.
Cells compensate for the lose of reducing equivalents by the induction
of enzymes which generate more. Numerous enzymes, cofactors, transcription
factors, and signal molecules are known which function quite differently
depending on whether or not they are in an oxidized or reduced condition.
reduce:
the process of giving out or donating electrons;
to release electrons or hydrogen atoms;
to refine an element by the removal of oxygen or halogen.
reducing equivalent ([e-] or [H]):
the item of transfer in an oxidation-reduction reaction;
an electron or a hydrogen atom.
reductant:
a contraction of the words reducing agent; any substance
which donates or gives away electron(s) or hydrogen atom(s);
the hydrogenator. Examples are: the negatively charged cathodic plate;
hydride anion; metal atoms; hydroquinones; polyphenols; amines; thiols.
reductase:
any enzyme which serves to add electrons or hydrogen atoms to
its substrate. Reductases are more precisely called oxidoreductases
because their action depends on a ready supply of some donor of reducing
equivalents which the enzyme first oxidizes. It subsequently transfers
these newly acquired reducing equivalents to the substrate.
reduction:
the process of an atom or molecule acquiring electrons or hydrogen
atoms.
reductive antioxidant (AOH):
any molecular species which serves to quench
oxygen centered radicals (oxyradicals) by the donation of a single
electron or atom of hydrogen. Examples of substances able to do this are:
thiols, phenols, ascorbate, and cuprous copper (Cu+).
Ref-1:
A reductase utilizing the thiol groups of two cysteine residues active
in the nucleus of the cell. Ref-1 activates AP-1 (an important DNA
transcription complex) by reduction. Reduction by Ref-1 also activates
the binding of numerous transcription factors including: NF-kappa-B, Myb,
ATF, CREB, EGR-1, etc. Hypoxia has been found to induce increased levels
of Ref-1. Oxidation reversibly inhibits the functions of Ref-1. The
sequence of reductase activities is NADPH...TR...Trx...Ref-1...AP-1.
resonance:
a phenomenon of which pi bonds are capable which allows an
electron to shift positions from one side of the bond to the other.
In the case of multiple pi bonds which are conjugated, an electron can
shift positions from one end of the conjugated system to the other and
among several locations in between. The effect permits shifting of a
negative charge, an unpaired electron, or a positive charge. The condition
is said to resonate or to be delocalized among the allowed positions.
Molecular structures which can resonate or delocalize electrons in this
way confer unusual stability to the charge or to the unpaired electron
which they possess. Also the chemical reactivity at the allowed positions
results in products which indicate that several different forms of the
reactant were involved, one for each allowed position. Molecules which
possess reactive groups which can be oxidized or reduced will do so more
readily if they also possess pi bond(s) conjugated with the redox active
group, because the semireduced or semioxidized radical intermediates
are stabilized by resonance.
rhein:
an anthroquinone found in rhubarb. Rhubarb is one of the ingredients
of the herbal combination known as "Essiac Tea" which has been used
to treat cancer and infections.
rhodozonic acid:
a 6 carbon ring composed of 4 carbonyl groups and 1 enediol;
the product of reduction of triquinoyl by 2 hydrogen atoms;
the product of abstraction of 2 hydrogen atoms from
tetrahydroxybenzoquinone. Rhodozonic acid redox cycles under
biologic conditions and therefore has been used as an
oxidative catalyst.
ribonucleoside-5'-diphosphate (NDP):
a three part nucleotide consisting of
a nitrogenous base (adenine, guanine, cytosine, or uracil) covalently
bound at the 1' carbon of ribose, plus a pyrophosphate ester (also called
a diphosphate) at the 5' carbon of ribose. NDP can receive a third
phosphoryl group from ATP to become a triphosphate (NTP). NTP's are the
precusors to RNA synthesis. NDP's can be reduced to deoxy- analogues
(dNDP's) by ribonucleotide reductase (RR). dNDP's can similarly be
phosphorylated by ATP to dNTP's, the precursors of DNA synthesis.
ribonucleotide reductase (RR):
an oxidoreductase which serves to convert
ribonucleoside-5'-diphosphates (NDP's) to their deoxy- analogues (dNDP's).
Two hydrogen atoms are donated in a process which replaces the 2' hydroxyl
group of ribose with a hydrogen atom, and which releases one molecule of
water. dNDP's are subsequently phosphorylated to dNTP's, the precursors
to DNA synthesis. Under physiologic conditions favorable to growth, RR
is reactivated by the acceptance of two hydrogen atoms from the thiol
groups of thioredoxin (Trx) or glutaredoxin (Grx). However, under
pro-oxidant conditions, wherein RR cannot be reduced, DNA synthesis is
profoundly inhibited.
