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.

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.

a contraction of the words reactive and agent; a reactant in pure form; substance which reacts in a predictable manner.

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.

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

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.

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.

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.

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.

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+).

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.

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.

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.