P53:
a genome or its corresponding protein which controls both
reproduction and apoptosis of the cell in response to a variety
of physiologic triggers. P53 contains redox active thiol groups
making P53 function sensitive to the redox balance of the cell.
Aberrant P53, as occurs when its corresponding genome is mutated,
can result in excessive cellular proliferation or resistance to
apoptosis, either or both of which are known to occur in cancer
cells. Thus mutant P53 is an oncogene.para-aminobenzoic acid (PABA):
an aromatic ring with a carboxyl group at
carbon one and an amino group at carbon four; a precursor to folate
synthesis in bacteria. Sulfonylamides are structural analogues of PABA
and as such competitively block incorporation of PABA in the synthesis
of folate. PABA, sulfonylamides, and aminobenzene compounds in general
are quenchers of singlet oxygen.
paramagnetic:
the characteristic of being attracted towards a magnetic field
but not able to hold a magnetic charge. Free radicals are all paramagnetic
due to the unpaired electron they possess which is also a tiny magnet.
paraquat:
1,1'-dimethyl-4,4'-dipyridilium dichloride; a dimer of N-methyl
pyridinium rings linked at the number four carbons and able to conjugate.
A positively charged quaternary nitrogen atom is present at each of the
two ends of the molecule bound to a methyl group. This structure can
readily accept electrons from various physiologic donors one or two at a
time. Its semireduced form is a relatively stable free radical due to the
extensive conjugation. Like a semireduced flavin (*FADH) or quinone (*QH),
semireduced paraquat readily passes electrons one at a time to oxygen
producing of superoxide (-OO*) and hydroperoxide (HOO*) radicals.
Paraquat is used as an herbicide in agriculture, and as a research tool in
biochemistry to study the effects of the introduction of superoxide or
the effectiveness of quenchers of superoxide. Delayed toxic effects
accrue to the lungs, liver, kidneys, and possibly the CNS when ingested.
paraquinone:
a compound composed of a ring of six carbon atoms, an oxo group
at carbons number 1 and 4, and double bonds between carbons 2 and 3 and
between carbons 5 and 6; two carbonyl groups connected by two ethylene
bridges forming a six membered ring. Paraquinones are medium strength
oxidants able to accept two hydrogen atoms to become hydroquinones or
paradihydroxybenzenes. Paraquinones possess four conjugated pi bonds
(more if side chains or rings are present) which facilitate stabilization
of the semireduced state. Paraquinones readily redox cycle under
biological conditions due to the presence of both reductants and
oxidants of various potentials. These are able to transfer electrons
to or from the paraquinones.
Pasteur effect:
the inhibition of fermentation by oxygenation.
pentose pathway:
another term for the hexose monophosphate shunt.
The pentose pathway produces large quantities of NADPH which activate
numerous reductases.
peroxide (ROOR'):
a family of compounds which possess two oxygen atoms
covalently bound to each other by sigma bonds forming a bridge within
the rest of the molecule. Organic peroxides can be reduced to alcohols
by the addition of two hydrogen atoms, one to each oxygen of the bridge.
One equivalent reductions produce an alcohol and an alkoxyl radical.
peroxidase:
any of a family of enzymes which reduce peroxides whether
hydrogen peroxide, lipid hydroperoxide, dialkylperoxide, or endoperoxide.
Peroxidases must have a source of reductant to accomplish this. In the
case of catalase, one molecule of hydrogen peroxide can serve as reductant
producing oxygen, while another is reduced to water. Glutathione peroxidase
accepts hydrogen atoms from glutathione (GSH) and uses these to reduce
numerous peroxide types. Other peroxidases can abstract electrons from a
wide variety of donors to accomplish peroxide reduction.
peroxynitric acid (HOONO):
an acid composed of a peroxide bridge between a
hydrogen atom and a nitrogen atom with attached oxo group. HOONO is
produced in vivo by activated killer cells by the coupling of two free
radicals hydroperoxyl (HOO*) and nitric oxide (*NO). HOONO decomposes
spontaneously to produce the nitrogen dioxide radical (*NO2) plus the
highly cytotoxic hydroxyl radical (HO*).
phase I detoxification:
the first step in catabolic elimination of certain
insoluble organic molecules such as steroid hormones, aromatic compounds,
and xenobiotics; the action of the mixed function oxidase system in
which cytochrome P 450 adds one atom of oxygen to the substrate converting
it to an epoxide or an aromatic hydroxide (phenol).
phase II detoxification:
the second step of catabolic elimination of various
compounds which were hydroxylated by the phase I system; conjugation
of various xenobiotics or metabolites with another molecule which renders
the product water soluble enabling elimination in the bile or urine.
In this context conjugation means the covalent attachment of a water
soluble group (not the coreactivity of pi bonds as in other contexts).
These addition reactions can be esterifications or thiol additions.
Precursors commonly used are glutathione, taurine, sulfate, glycine,
and glucaronic acid.
phenazine:
a tricyclic compound naturally occurring in pseudomonas species
of bacteria. The central ring contains 2 nitrogen atoms as imines
which are conjugated and redox active. Thus each molecule of
phenazine can reversibly take up and carry 2 atoms of hydrogen.
phenol (Ar-OH):
an aromatic compound having a hydroxyl group attached to
one of the carbon atoms of the aromatic ring.
phenoxyl radical (Ar-O*):
the semioxidized form of phenol which has one
atom of hydrogen removed from the hydroxyl oxygen. Phenoxyl radical
is stabilized by resonance of the unpaired electron among four sites
among its three conjugated pi bonds. Phenoxyl radical can be readily
reduced to phenol by numerous stronger reductants. Phenoxyl radicals
can couple to produce dimers known as diphenoquinones.
phorbol (TPA):
12-O-tetradecanoylphorbol-13-acetate; a growth promotor
which can be applied externally to cells in vivo or in vitro to
stimulate mitosis and transformation to neoplasia. TPA initiates a
complex series of intracellular responses some of which involve redox
sensitive compounds.
6-phosphogluconate dehydrogenase:
an oxidoreductase which catalyses the
transfer of reducing equivalents from 6-phosphogluconate to NADP+; a key
producer of NADPH as part of the hexose monophosphate shunt.
phosphorylation:
the addition of a phosphoryl group (PO3--). This process facilitates
energy metabolism, metabolite preparation, biosynthesis, and
physiologic signal transduction.
photoluminescense:
the phenomenon of the absorbtion of the energy from
photons by certain molecules which hold or process this energy releasing
it later usually at a frequency or wavelenth different from that
originally absorbed.
photoreduction:
the stimulation of the uptake of hydrogen atoms by light.
Compounds containing pi bonds (especially conjugated pi bonds) can absorb
photon energy and be chemically photoactivated. This converts them to a
triplet state also known as a diradical. As a diradical the energized
molecule becomes a much stronger oxidant causing it to abstract hydrogen
more readily from other potential donors. Photoactivation thus causes a
redox reaction to take place which ordinarily would never occur.
pi bond:
a type of covalent bond usually formed from two p orbitals which
are oriented in the same plane perpendicular to the long axis of a sigma
bond. The orbitals form two clouds which are sausage or bean shaped, one
on each side of the sigma bond which is spindle shaped. The pi bond is
of a slightly higher potential energy level than a sigma bond and is
therefore more easily broken and chemically more reactive. Pi bonds
can trap free radicals, polymerize, accept hydrogen atoms, conjugate,
and absorb photons to become diradicals.
picogram (pcg):
one trillionth of a gram; one millionth of a millionth of a
gram; 10 exp -12 gram.
plastoquinone (PQ-9):
2,3-dimethyl-6-nonaprenyl-1,4-benzoquinone.
An important carrier of reducing equivalents in chloroplasts as part of
the photosynthetic process. Plastoquinone is present in all green plants,
in the fresh juices of green plants, and with crude extracts of green
plants.
plumbagin:
5-hydroxy-2-methyl-1,4-naphthoquinone; droserone; a NQ naturally
occuring in lead wort (numerous species of Plumbaginaceae), in venus fly
trap (Dionaea muscipula), several species of Droseraceae, Diospyros,
Drosophyllum, Ceratostigma, etc. Numerous herbal remedies utilize these
species. Carnivora is a standardized extract of Dionaea muscipula in
ethyl alcohol made in Germany. In India the root of plumbago is the
medicament commonly known as Chita or Chitraka. Plumbagin has shown
immunostimulatory, antiviral, antibacterial, and antineoplastic effects.
polyamine:
a class of ubiquitous amines which are synthesized prior to and during
mitosis. Polyamines are necessary for cell growth, division, protein
synthesis, and the integrity of certain organelles. Common naturally
occuring polyamines are spermine, spermidine, cadaverine and putrescine.
polyamine oxidase (PAO):
any of a class of enzymes which degrades polyamines
converting them to aldehydes by the process of oxidative deamination.
PAO's can attack primary and secondary amino groups.
polyphenol:
an aromatic compound with two or more hydroxyl groups
substituting for hydrogen in the benzene ring. Naturally occuring
diphenols have two hydroxyl groups in either the ortho (1,2), meta (1,3)
or para (1,4) positions. In triphenols the hydroxyl groups are usually
adjacent (1,2,3). Common examples are the many esters of gallic acid.
Many naturally occuring polyphenols also have a flavone, anthocyanidin,
or other bioflavonoid structure. Many are polymers of bioflavonoids.
Polyphenols are more active than monophenols as reductive antioxidants.
Ortho-diphenols (also known as catechols or orthohydroquinones) and
para-diphenols (also known as parahydroquinones) readily autooxidize
to become ortho- and para-quinones respectively. Oxidized polyphenols
are bitter tasting, astringent, and often irritating, have documented
antibacterial and antineoplastic effects, and react with primary amines
to form imines which can polymerize. The products of oxidized polyphenols
and amines are often brown or tan in color, hense the name tannins as
applied to mixtures of polyphenols or oxidized polyphenols.
polyunsaturated fatty acid (PUFA):
a long chain hydrocarbon with a terminal
carboxyl group and two or more carbon-carbon double bonds along its length.
The double bonds exist only in the cis configuration. They are seperated
by two or more single bonds, thus they are not conjugated. Any hydrogen
atom alpha to a double bond, especially the one in between two double
bonds, is more readily extractable by strong oxidants as compared to
fully saturated hydrocarbons. This vulnerability allows for PUFA's to be
further modified to become conjugated dienes or lipid peroxides.
polyvalent:
able to exist in more than one oxidation state.
porphin and porphyrin:
a class of compounds composed of four heterocyclic
rings each ring containing five members (four of carbon and one of
nitrogen) with the nitrogen held centrally. The structure possesses
eleven conjugated pi bonds with interesting spectral, photochemical,
free radical stabilizing, and redox active characteristics. The center
provides four nitrogenous ligands which bind cationic metals such as
magnesium, iron, or copper. Metalloporphins are utilized in electron
transfer, oxygen transfer, and photosynthesis.
primary amine (R-CH2-NH2):
a nitrogen atom covalently bound to two atoms
of hydrogen and one of carbon. Examples are: amino acids, polyamines,
neurotransmitters, ptomaines, guanine, cytosine, etc.
probe:
a substance selected for its specific form and chemical action,
which is introduced in vivo or in vitro (in the presence of biological
molecules such as enzymes and substrates). They are used, to study
the function of a particular enzyme, metabolic pathway, receptor,
or trigger. Probes enable us to discover the molecular mechanisms
underlying numerous biochemical functions. Probes are usually
analogues of naturally occurring metabolites, or they may be
radio-isotopes, drugs, or dyes.
pro-oxidant:
any substance or condition favorable to a process of oxidation.
Examples are: the introduction of oxidants, the charging of an anodic
plate, the removal of or inactivation of normally available reductants,
the cutting off of any influx of new reductants, the introduction of
catalysts which facilitate the transfer of electrons from the substances
being oxidized to the available oxidants.
propagation:
a chemical reaction which perpetuates itself by the reaction of
free radicals which produce new free radicals which go on to react again.
pro-reductant:
any substance or condition favorable to the process of
reduction. Examples are: the introduction of reductants, the charging of
a cathodic plate, the removal or inactivation of normally available
oxidants, the cutting off of any influx of new oxidants, the introduction
of catalysts which facilitate the transfer of electrons from the available
reductants to the substances being reduced, the removal or inactivation
of catalysts which otherwise facilitate oxidation. The detoxification of
certain metallic cations by chelation, and the phase II conjugation of
quinones, are examples of the elimination of pro-oxidant catalysts.
prostaglandin (PG):
a class of docosoids which function as mediators of
physiologic cell signal mechanisms. These control functions as diverse as
inflammation and blood coagulation. Some of the prostaglandin conversion
pathways involve redox reactions or oxygenations.
prosthetic group:
a molecular species attached to a polypeptide to produce
an active enzyme. Examples are: the binding of FAD to an apoprotein to
produce a dehydrogenase, or the insertion of a metalloporphin into yet
another apoprotein to produce a cytochrome.
protein disulfide isomerase (PDI):
an oxidoreductase containing two redox
active cysteine residues localized to the endoplasmic reticulum where
it serves to regulate the correct folding of proteins as they emerge
from ribosomes. PDI can be activated by thioredoxin reductase. PDI serves
as part of the conversion process of proline to hydroxy proline in
collagen synthesis. PDI is a cofactor in the release of triacylglycerols
from the liver. PDI is able to convert dehydroascorbate to ascorbic acid.
protein kinases:
a family of enzymes which catalyze the phosphorylation of
specific amino acid residues of their target proteins as part of numerous
intracellular signal mechanisms. Common targets of this action are:
tyrosine, serine, histidine, and threonine.
ptomaines:
products of protein putrifaction including amines produced
by the decarboxylation of amino acids.
putrescine (NH2-CH2-CH2-CH2-CH2-NH2):
a polyamine and precursor to other
polyamines; the decarboxylation product of ornithine; an amine produced
by putrifying bacteria.
pyridines:
heterocyclic compounds composed of 5 carbon atoms and 1
nitrogen atom. Niacin (vitamin B3) and the dinucleotides
of nicotinamide (NADH and NADPH) are derivatives of pyridines.
pyridinium:
a quaternary ammonium analogue of pyridine; a heterocyclic
aromatic ring similar to benzene but replacing one of the ring members
with a nitrogen atom covalently bound to an alkyl group. Thus a quaternary
ammonium atom of positive charge substitutes for the normally neutral
and quadrivalent carbon atom. Pyridinium rings are readily able to
accept one electron, due to their positive charge and their extensively
conjugated pi bonds, to form a neutral semireduced radical. This function
explains the first electron transfer to the physiologic electron carrier
NAD+ which contains a pyridinium ring (nicotinamide) at its redox active
site. The semireduced radical subsequently accepts a whole hydrogen atom
to become NADH. The herbicide paraquat (which is a dimer of two pyridinium
rings) redox cycles by this same mechanism. It passes electrons one at a
time to diatomic oxygen so producing extensive quantities of superoxide
(-OO*). The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
is dehydrogenated by monoamine oxidase (MAO) to 1-methyl-4-phenylpyridinium
(MPP+). Like paraquat, MPP+ is believed to redox cycle and produce an
overabundance of superoxide. The substantia nigra, being especially
vulnerable to superoxide/hydroperoxyl toxicity, degenerates resulting in
Parkinson's disease (paralysis agitans). The CNS toxicity of MPTP in
experimental animals is inhibited by the MAO inhibitor selegiline/
deprenyl/Eldepryl.
pyrrole:
azole; imidole; a 5 atom heterocyclic compound composed of 4
carbons and 1 nitrogen, the carbons bare double bonds but not
the nitrogen. A group present in numerous biologic molecules
including porphyrins, heme, porphobilinogen, and bilirubins.
pyrroloquinoline quinone (PQQ):
a tricyclic compound composed of 11 carbon atoms and
2 nitrogen atoms among its three rings, three carboxyl
groups bound externally, and an orthoquinone group at the
middle ring. The rings are unsaturated resulting in
extensively conjugated pi bonds. The orthoquinone form is
readily reducible to an enediol. PQQ can redox cycle in vivo.
It is synthesized by certain bacteria in which it has been
shown to be part of the redox active center of certain
glucose and alcohol dehydrogenases. Until recently PQQ was
erroneously thought to be part of the redox active center
of the mammalian diamine oxidases. PQQ is a naturally
occuring compound in the diet. PQQ has been shown to convey
significant physiologic benefits such as improved resistance
to lead toxicity, ischemia-reperfusion injury, cataract
formation, corticosteroid injury, hepatotoxins, and infection.
PQQ supports the function of lysyl oxidase, though is
probably not part of its structure.
pyruvic acid (CH3-CO-COOH):
alpha-keto-n-propanoic acid; the final product of
glycolysis under aerobic conditions; the precursor to lactic acid under
anaerobic conditions when used instead of oxygen as an electron acceptor.
Pyruvic acid can be shuttled unto the mitochondria where it is further
processed as a fuel molecule.
