Biomedical subjects

K U Ingold

Publications and source records attributed to K U Ingold.

At least 37 records · Page 2Linked to original sources

PubMed2003

Abnormal solvent effects on hydrogen atom abstractions. 1. The reactions of phenols with 2,2-diphenyl-1-picrylhydrazyl (dpph*) in alcohols.

Rate constants, k(ArOH/dpph*)(S), for hydrogen atom abstraction from 13 hindered and nonhindered phenols by the diphenylpicrylhydrazyl radical, dpph*, have been determined in n-heptane and a number of alcoholic and nonalcoholic, hydrogen-bond accepting solvents. Abnormally enhanced k(ArOH/dpph*)(S) values of have been observed in alcohols. It is proposed that this is due to partial ionization of the phenols and a very fast electron transfer from phenoxide anion to dpph*. The popular assessment of the antioxidant activities of phenols with dpph* in alcohol solvents will generally lead to an overestimation of their activities.

Journal Article↗

PubMed2003

Mechanism of inhibition of lipid peroxidation by gamma-terpinene, an unusual and potentially useful hydrocarbon antioxidant.

gamma-Terpinene (TH), a monoterpene hydrocarbon present in essential oils, retards the peroxidation of linoleic acid (LH). The peroxidation of TH has been shown to yield p-cymene as the only organic product in a chain reaction in which the chain carrier is the hydroperoxyl radical, HOO(.). The peroxidation of LH is well-known to be a chain reaction in which the chains are carried by linoleylperoxyl radicals, LOO., and the products are linoleyl hydroperoxides. The retardation of LH peroxidation by TH has been found to be due to rapid chain termination via a very fast cross-reaction between HOO. and LOO. radicals. This antioxidant mechanism is completely different from the mechanism of antioxidant action of vitamin E. Since vitamin E becomes a prooxidant at high concentrations, the addition of essential oils containing TH to edible lipids may provide an alternative or supplementary strategy for obtaining large increases in their oxidative stability and shelf life, something that cannot be achieved by simply adding more and more vitamin E.

Cyclohexane Monoterpenes↗

PubMed2003

Reactions of water-soluble alkylperoxyl radicals and superoxide with DNA, lipoproteins and phospholipid vesicles: the role played by electrostatic forces.

The role of electrostatic forces in free radical biology is very important but it is all too often overlooked. The radicals discussed in this review include positively-charged, negatively-charged and neutral water-soluble alkylperoxyls and superoxide. Important scientific insights have been gained by generating these radicals in known quantities by the thermal decomposition of simple, "clean", chemical precursors in the presence of potential bio-targets. For example, the abilities of these radicals to damage double-stranded DNA, a polyanion, are dictated by Coulombic forces with only the positively-charged peroxyls being capable of directly producing single-strand breaks. The Coulombic control of the reactions and reaction rates of water-soluble peroxyl radicals which are so evident with DNA do not manifest themselves with all electrostatically charged bio-targets, e.g., low density lipoprotein (LDL), probably because the charge on the surface of the LDL is not uniformly distributed.

DNA↗

PubMed2002

The role of hydrogen bonding on the h-atom-donating abilities of catechols and naphthalene diols and on a previously overlooked aspect of their infrared spectra.

Catechols and 1,8-naphthalene diols contain one "free" hydroxyl and one intramolecularly H-bonded hydroxyl group. The "free" hydroxyls are strong hydrogen-bond donors (HBDs) with alpha2H values (Abraham et al. J. Chem. Soc., Perkin Trans. 2 1989, 699) ranging from 0.685 to 0.775, indicating that these compounds have similar HBD properties to those of strongly acidic phenols such as 4-chlorophenol (alpha2H = 0.670) and 3, 5-dichlorophenol (alpha2H = 0.774). Kinetic effects on H-atom abstractions from the diols in HB acceptor (HBA) solvents can be quantitatively accounted for over at least 50% of the available range of solvent HBA activities (as measured by their beta2H values; see Abraham et al. J. Chem. Soc. Perkin Trans. 2 1990, 521) on the basis of a single reactive OH group, the "free" OH. This free OH group is an outstanding H-atom donor in poor HBA solvents; e.g., in hexane rate constants for reaction with the DPPH* radical are 2.1 x 104 M-1 s-1 for 3,5-di-tert-butyl catechol and 2 x 106 M-1 s-1 for 4-methoxy-1,8-naphthalene diol, but only 7.4 x 103 M-1 s-1 for alpha-tocopherol (vitamin E). The diols are much more reactive than simple phenols because the O-H bond dissociation enthalpy of the "free" OH group is weakened by 5-9 kcal/mol by the intramolecular H-bond. The IR spectra of all the diols in CCl4 show two fairly sharp O-H stretching bands of roughly equal intensity separated by 42-138 cm-1. Addition of a low concentration of DMSO, a strong HBA, causes the band due to the intramolecularly H-bonded OH group to decrease in intensity to roughly half the extent that the "free" OH band loses intensity. The latter forms an intermolecular H-bond with the DMSO, the former does not. What has been overlooked in earlier work is that as the DMSO concentration is increased the band due to the intramolecularly H-bonded OH group first broadens and then evolves into a new, lower frequency (by 19-92 cm-1) band. The magnitude of the shift in the frequency of the intramolecular OH band caused by H-bonding of HBAs to the "free" OH group, Deltanu, increases linearly as the HBA activity of the additive increases, e.g., for 3,5-di-tert-butylcatechol, Deltanu/cm-1 = 33.8 beta2H (R 2 = 0.986). This may provide a new and simple method for determining beta2H values.

Journal Article↗

PubMed2002

Substituent effects on the bond dissociation enthalpies of aromatic amines.

Bond dissociation enthalpy differences, Z-X DeltaBDE = BDE(4-YC(6)H(4)Z-X) - BDE(C(6)H(5)Z-X), for Z = CH(2) and O are largely independent of X and are determined mainly by the stabilization/destabilization effect of Y on the 4-YC(6)H(4)Z(*) radicals. The effects of Y are small (< or =2 kcal/mol for all Y) for Z = CH(2), but they are large for Z = O, where good correlations with sigma(p)(+)(Y) yield rho(+) = 6.5 kcal/mol. For Z = NH, two sets of electrochemically measured N-H DeltaBDEs correlate with sigma(p)(+)(Y), yielding rho(+) = 3.9 and 3.0 kcal/mol. However, in contrast to the situation with phenols, these data indicate that the strengthening effect on N-H BDEs of electron-withdrawing (EW) Y's is greater than the weakening effect of electron-donating (ED) Y's. Attempts to measure N-H DeltaBDEs in anilines using two nonelectrochemical techniques were unsuccessful; therefore, we turned to density functional theory. Calculations on 15 4-YC(6)H(4)NH(2) gave N-H DeltaBDEs correlating with sigma(p)(+) (rho(+) = 4.6 kcal/mol) and indicated that EW and ED Y's had comparable strengthening and weakening effects, respectively, on the N-H bonds. To validate theory by connecting it to experiment, the N-H DeltaBDEs of four 4,4'-disubstituted diphenylamines and five 3,7-disubstituted phenothiazines were both calculated and measured by the radical equilibration EPR technique. For all compounds, theory and experiment agreed to better than 1 kcal/mol. Dissection of N-H DeltaBDEs in 4-substituted anilines and O-H DeltaBDEs in 4-substituted phenols into interaction enthalpies between Y and NH(2)/OH (molecule stabilization/destabilization enthalpy, MSE) and NH*/O* (radical stabilization/destabilization enthalpy, RSE) reveals that for both groups of compounds, ED Y's destabilize the molecule and stabilize the radical, while the opposite holds true for EW Y's. However, in the phenols the effects of substituents on the radical are roughly 3 times as great as those in the molecule, whereas in the anilines the two effects are of comparable magnitudes. These differences arise from the stronger ED character of NH(2) vs OH and the weaker EW character of NH* vs O*. The relatively large contributions to N-H BDEs in anilines arising from interactions in the molecules suggested that N-X DeltaBDEs in 4-YC(6)H(4)NH-X would depend on X, in contrast to the lack of effect of X on O-X and CH(2)-X DeltaBDEs in 4-YC(6)H(4)O-X and 4-YC(6)H(4)CH(2)-X. This suggestion was confirmed for X = CH(3), H, OH, and F, for which the calculated NH-X DeltaBDEs yielded rho(+) = 5.0, 4.6, 4.0, and 3.0 kcal/mol, respectively.

Journal Article↗

PubMed2002

Naphthalene diols: a new class of antioxidants intramolecular hydrogen bonding in catechols, naphthalene diols, and their aryloxyl radicals.

1,8-Naphthalenediol, 5, and its 4-methoxy derivative, 6, were found to be potent H-atom transfer (HAT) compounds on the basis of their rate constants for H-atom transfer to the 2,2-di(4-t-octylphenyl)-1-picrylhydrazyl radical (DOPPH*), k(ArOH/DOPPH)*, or as antioxidants during inhibited styrene autoxidation, k(ArOH/ROO)*, initiated with AIBN. The rate constants showed that 5 and 6 are more active HAT compounds than the ortho-diols, catechol, 1, 2,3-naphthalenediol, 2, and 3,5-di-tert-butylcatechol, 3. Compound 6 has almost twice the antioxidant activity, k(ArOH/ROO)* = 6.0 x 10(6) M(-)(1) s(-1), of that of the vitamin E model compound, 2,2,5,7,8-pentamethyl-6-chromanol, 4. Calculations of the O-H bond dissociation enthalpies compared to those of phenols, (deltaBDEs), of 1-6 predict a HAT order of reactivity of 2 < 1 < 3 approximately 4 < 5 < 6 in general agreement with kinetic results. Calculations on the diols show that intramolecular H-bonding stabilizes the radicals formed on H-atom transfer more than it does the parent diols, and this effect contributes to the increased HAT activity of 5 and 6 compared to the activities of the catechols. For example, the increased stabilization due to the intramolecular H-bond of 5 radical over 5 parent of 8.6 kcal/mol was about double that of 2 radical over 2 parent of 4.6 kcal/mol. Linear free energy plots of log k(ArOH/DOPPH)* and log k(ArOH/ROO)* versus deltaBDEs for compounds 1-6 along with available literature values for nonsterically hindered monophenols placed the compounds on common scales. The derived Evans-Polanyi constants from the plots for the two reactions, alpha(DOPPH)* = 0.48 > alpha(ROO)* = 0.32, gave the expected order, since the ROO* reaction is more exothermic than the DOPPH* reaction. Compound 6 is sufficiently reactive to react directly with oxygen, and it lies off the log k(ArOH/ROO)* versus deltaBDE plot.

Antioxidants↗

PubMed2002

The contrasting kinetics of peroxidation of vitamin E-containing phospholipid unilamellar vesicles and human low-density lipoprotein.

It is well established that alpha-tocopherol, TocH, is an outstanding lipid-soluble, peroxyl radical trapping antioxidant in homogeneous systems. It is also well established that TocH functions as a prooxidant in human low-density lipoprotein, LDL, subjected to attack by peroxyl radicals generated in the aqueous phase by, for example, thermal decomposition of the azo compound, ABAP. This tocopherol-mediated peroxidation, TMP, of LDL involves a three-step chain reaction, one step being hydrogen atom abstraction from the LDL lipids by the tocopheroxyl radical, Toc*. The occurrence of TMP has been attributed to three factors, (i) translocation by TocH of radical character from the aqueous phase into LDL lipid, (ii) isolation of the water-insoluble Toc* in the LDL particle in which it is formed for times sufficient to permit it to react with the lipid, and (iii) the small lipid volume of LDL which ensures that no particle can contain more than a single radical for a significant length of time. This consensus view of TMP implies that it should occur in any TocH-containing dispersion of small lipid particles. However, the present examination of the kinetics of the ABAP-initiated peroxidation of small unilamellar vesicles, SUVs, made from palmitoyllinoleoylphosphatidylcholine and cholesterol with a composition designed to mimic the surface coat of LDL, has shown that TocH functions as an antioxidant in such systems and that TMP does not occur under conditions where it would have occurred if the particles had been LDL. Several possible reasons for the kinetic differences between SUVs and LDL have been considered and ruled out by experiment. It is concluded that TMP can occur in LDL because these particles contain a lipid core in which the Toc* radical "hides" for much of its lifetime well away from the peroxyl radicals in the aqueous phase. In contrast, because SUVs have no lipid core, the Toc(*) radical is always "exposed" and available to aqueous peroxyl radicals with which it reacts rapidly and is destroyed before it can abstract a hydrogen atom from the lipid.

Antioxidants↗

PubMed2002

Absolute rate constants of alkene addition reactions of a fluorinated radical in water.

Absolute rate constants of *R(f)SO(3)(-) radical addition to a series of water-soluble alkenes containing ionic, carboxylate substituents were measured by laser flash photolysis experiments in water. The observed rate constants were all considerably larger than those of structurally similar analogues in a nonpolar organic solvent, with rate factors of 3-9-fold being observed. It is concluded that such rate enhancements derive at least in part from stabilization of the polar transition state for addition of the electrophilic fluorinated radical to alkenes by the polar solvent water.

Journal Article↗

PubMed2002

Cleavage of supercoiled DNA by horseradish peroxidase plus tert-butyl hydroperoxide is not due to tert-butylperoxyl radicals.

Two supercoiled (SC), double-stranded DNAs, pBR 322 and pUC 19, have been subjected to oxidative stress using horseradish peroxidase (HRP) and HRP + tert-butyl hydroperoxide (BOOH). HRP alone causes single-strand cleavage of these SC DNAs. Strand cleavage is enhanced substantially in the presence of commercial BOOH (which contains H(2)O(2)) but is, at best, only very slightly enhanced in the presence of pure BOOH. In the HRP/pure BOOH system, the DNA single-strand-scission which does occur appears to be due to a direct action of oxidized HRP. It is not due to tert-butylperoxyl radicals because strand-scision is not even retarded by 10 mM Trolox, an outstanding water-soluble trap for peroxyl radicals. The present results are congruent with our earlier conclusion [Paul, T., et al. (2000) Biochemistry 39, 4129] that neutral alkylperoxyl radicals produce little or no direct single-strand-scission in SC DNAs.

DNA Damage↗

PubMed2001

Quantitative studies on the peroxidation of human low-density lipoprotein initiated by superoxide and by charged and neutral alkylperoxyl radicals.

Rates of peroxidation of human LDL and rates of consumption of the LDL's alpha-tocopherol (TocH) have been measured at 37 degrees C. Peroxidation was initiated by radicals generated in the aerated aqueous phase at known rates by thermal decomposition of appropriate precursors: superoxide (O2(*-)/HOO(*)) from a hyponitrite and alkylperoxyls (ROO(*), two positively charged, one negatively charged and one neutral) from azo compounds. The efficiencies of escape from the solvent cage of the geminate pair of neutral carbon-centered radicals was found to be 0.1, but it was 0.5 for the three charged radicals, a result attributed to radical/radical Coulombic repulsion within the cage. All four alkylperoxyls initiated and terminated tocopherol-mediated peroxidation (TMP) with about equal efficiency and essentially all of these radicals that were generated were consumed in these two reactions. TMP is a radical chain process, and when initiated by the alkylperoxyls, the rate of LDL peroxidation was faster in the early stages while TocH was present than later, after all of this "antioxidant" had been consumed. In contrast, only about 3-4% of the generated superoxide radicals reacted in any measurable fashion with TocH-containing LDL at pH's from 7.6 to 6.5 and peroxidation was much slower than with a similar rate of generation of alkylperoxyls. After all the TocH had been consumed, LDL peroxidation was negligible at pH 7.6 and 7.4, but at pH 6.8 and 6.5, the peroxidation rates showed a large increase over the rates while the TocH had been present. That is, endogenous TocH behaves as an antioxidant in LDL subjected to attack by the physiologically relevant superoxide radical, whereas TocH behaves as a prooxidant in LDL subjected to attack by the probably far less physiologically important alkylperoxyls. Rates of LDL peroxidation initiated by superoxide increased as the pH was decreased, and the results are consistent with the initiation of peroxidation of fresh LDL occurring via H-atom abstraction from TocH by HOO(*) to form the Toc(*) radical and termination by reaction of O2(*-) with Toc(*), a process that occurs partly by addition leading to TocH consumption and partly by electron plus proton transfer leading to the regeneration of TocH.

Antioxidants↗

PubMed2001

Oxygen-carbon bond dissociation enthalpies of benzyl phenyl ethers and anisoles. An example of temperature dependent substituent effects.

For some time it has been assumed that the direction and magnitude of the effects of Y-substituents on the Z-X bond dissociation enthalpies (BDE's) in compounds of the general formula 4-YC(6)H(4)Z-X could be correlated with the polarity of the Z-X bond undergoing homolysis. Recently we have shown by DFT calculations on 4-YC(6)H(4)CH(2)-X (X = H, F, Cl, Br) that the effects of Y on CH(2)-X BDE's are small and roughly equal for each X, despite large changes in C-X bond polarity. We then proposed that when Y have significant effects on Z-X BDE's it is due to their stabilization or destabilization of the radical. This proposal has been examined by studying 4-YC(6)H(4)O-X BDE's for X = H, CH(3), and CH(2)C(6)H(5) both by theory and experiment. The magnitudes of the effects of Y on O-X BDE's were quantified by Hammett type plots of DeltaBDE's vs sigma(+) (Y). Calculations reveal that changes in O-X BDE's induced by changing Y are large and essentially identical (rho(+) = 6.7-6.9 kcal mol(-)(1)) for these three classes of compounds. The calculated rho(+) values are close to those obtained experimentally for X = H at ca. 300 K and for X = CH(2)C(6)H(5) at ca. 550 K. However, early literature reports of the effects of Y on O-X BDE's for X = CH(3) with measurements made at ca. 1000 K gave rho(+) approximately 3 kcal mol(-)(1). We have confirmed some of these earlier, high-temperature O-CH(3) BDE's and propose that at 1000 K, conjugating groups such as -OCH(3) are essentially free rotors, and no longer lie mainly in the plane of the aromatic ring. As a consequence, the 298 K DFT-calculated DeltaBDE for 4-OCH(3)-anisole of -6.1 kcal mol(-)(1) decreases to -3.8 kcal mol(-)(1) for free rotation, in agreement with the ca. 1000 K experimental value. In contrast, high-temperature O-CH(3) DeltaBDE's for three anisoles with strongly hindered substituent rotation are essentially identical to those that would be observed at ambient temperatures. We conclude that substituent effects measured at elevated temperatures may differ substantially from those appropriate for 298 K.

Journal Article↗

PubMed2000

How should xanthine oxidase-generated superoxide yields be measured?

The rate of formation of superoxide measured by its reduction of tetranitromethane (TNM) and by its reduction of ferric cytochrome c (Fe(III) cc) are in excellent agreement when the superoxide is generated from a simple chemical precursor. In contrast, the rate of formation of superoxide generated in the reaction of xanthine oxidase with acetaldehyde is much higher (up to a factor of 6) when measured with TNM and compared with Fe(III) cc. It is shown that Fe(III) cc measures superoxide that has diffused from the enzyme, and that TNM probably scavenges all the dioxygen that is reduced by one electron by the enzyme. The TNM traps enzyme-bound superoxide in competition with the second-electron transfer and proton transfer, which normally yield hydrogen peroxide. The proton transfer is probably rate determining, k(p) </= 3.8x10(3)s(-1).

Acetaldehyde↗

PubMed2000

Strand cleavage of supercoiled DNA by water-soluble peroxyl radicals. The overlooked importance of peroxyl radical charge.

It is well established that the peroxyl radicals formed during the thermal decomposition of 2,2'-azobis(amidinopropane), ABAP, in oxygenated water can cleave double-stranded DNA, from which fact it has been concluded that peroxyl radicals, as a general class, can induce DNA strand scission. However, the ABAP-derived radicals are positively charged, and DNA is a negatively charged polyanion. Moreover, the relatively small and, therefore, free to diffuse peroxyl radicals likely to be formed in vivo will generally be negatively charged or neutral. Plasmid supercoiled DNA [pBR 322, 4361 base pairs (bp)] was reacted with known, equal fluxes of two positively charged peroxyl radicals, a negatively charged peroxyl radical, and a neutral peroxyl radical. The two positively charged peroxyl radicals degraded >/=80% of the supercoiled pBR 322 at a flux of 4 radicals/bp, but the negatively charged and neutral peroxyl radicals had no significant effect even at a flux as high as 24 radicals/bp. The same lack of effect on the DNA was also observed with high fluxes of superoxide/hydroperoxyl radicals. Similar results were obtained with another supercoiled DNA, pUC 19, except that pUC 19 is somewhat more sensitive to strand scission by positively charged peroxyl radicals than pBR 322. We conclude that most of the peroxyl radicals likely to be formed in vivo have little or no ability to induce DNA strand scission and that the potential role of electrostatics in radical/DNA reactions should always be considered.

Animals↗

PubMed2000

A novel procedure for generating both nitric oxide and superoxide in situ from chemical sources at any chosen mole ratio. First application: tyrosine oxidation and a comparison with preformed peroxynitrite.

The first method for generating (*)NO and O(2)(*)(-) at any known, constant ratio has been developed. Spermine NONOate and di(4-carboxybenzyl)hyponitrite decay with first-order kinetics and exactly equal rate constants (half-lives of 80 min) at 37 degrees C and pH 7.5 to give 200 and 40 mol % (*)NO and O(2)(*)(-), respectively. Tyrosine oxidation to dityrosine and 3-nitrotyrosine (the major and minor products under the conditions used in these experiments) has been studied (mainly in the presence of CO(2)) using various different ratios of the rates of formation of (*)NO and O(2)(*)(-). The (*)NO/O(2)(*)(-) = 1.0 product profiles are very similar to those of the products derived from equal amounts of (*)NO and O(2)(*)(-) generated at a (*)NO/O(2)(*)(-) ratio of 1.0 from SIN-1 but are very different from those derived from preformed peroxynitrite. All the experimental results can be explained in terms of free radical chemistry. The product profiles at all the (*)NO/O(2)(*)(-) ratios could be satisfactorily simulated provided an important group of reactions which lead to the consumption of dityrosine was included.

Molsidomine↗

PubMed2000

Superoxide, amine buffers and tetranitromethane: a novel free radical chain reaction.

The amine buffer Tris slowly reduces tetranitromethane (TNM) to the nitroform anion in a non-accelerating reaction. The amine buffers HEPES and MOPS also (slowly) react with TNM but the dialkylaminoalkyl radicals formed from these two buffers undergo further reactions resulting in a rapid, accelerating, free radical chain process whereby the amine is oxidized and TNM reduced. The chemical functionality in any reaction component, not necessarily the buffer, required for this radical chain mechanism is >N-CH<. In the presence of such groups, the quantification of superoxide by TNM is impossible.

Amines↗

PubMed1999

On the antioxidant activity of melatonin.

Melatonin has been widely reported to be an effective antioxidant. Studies of its ability to inhibit the autoxidation of lipids in homogeneous solution and in model heterogeneous systems show that melatonin is not a peroxyl radical trapping antioxidant. In contrast, melatonin can inhibit metal ion-catalyzed oxidation processes.

Antioxidants↗

PubMed1998

Human plasma and tissue alpha-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E.

We report a comparison of natural and synthetic vitamin E in humans using deuterium labeling to permit the two forms of vitamin E to be measured independently in plasma and tissues of each subject. Differences in natural and synthetic vitamin E concentrations were measured directly under equal dosage conditions using an equimolar mixture of deuterated RRR-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate. Two groups of five adults took 30 mg of the mixture as a single dose and as eight consecutive daily doses, respectively. After a 1-mo interval the schedule was repeated but with a 10-fold higher dose (ie, 300 mg). In each case, the ratio of plasma d3-RRR-alpha-tocopherol to d6-all-rac-alpha-tocopherol (RRR:rac) increased from approximately 1.5-1.8 to approximately 2 after dosing ended. In an elective surgery study in which 22 patients were given 150 mg/d for up to 41 d before surgery, the RRR:rac in tissues was lower than in plasma and the percentage of deuterated alpha-tocopherol was lower in all tissues except gallbladder and liver. In a terminally ill patient given 30 mg/d for 361 d, plasma and tissue (x+/-SD) RRR-rac ratios (and % deuterated alpha-tocopherol) at autopsy were 2.06 (6.3%) and 1.71+/-0.24 (5.9+/-2.2%), respectively. In a second terminally ill patient given 300 mg/d for 615 d, the corresponding values were 2.11 (68%) and 2.01+/-0.17 (65+/-10%), respectively. The results indicated that natural vitamin E has roughly twice the availability of synthetic vitamin E. This 2:1 ratio is significantly higher than the currently accepted RRR:rac of 1.36:1.00. Gamma-Tocopherol, expressed as a fraction of total unlabeled tocopherols in 15 elective surgery patients, was 1.4-4.6 (mean: 2.6) times greater in adipose tissue, muscle, skin, and vein than in plasma, which is a substantially larger fraction than had been recognized previously.

Adult↗

PubMed1997

alpha-Tocopheryl quinone is converted into vitamin E in man.

The conversion of alpha-tocopheryl quinone into alpha-tocopherol in humans has been demonstrated. A male subject was given an oral dose of 400 mg of alpha-3,5-[(C2H3)2]-tocopheryl quinone with an evening meal. Analysis of plasma 15 h later by lipid extraction and subsequent GC-MS single ion monitoring revealed the presence of alpha-[5,7-(C2H3)2]-tocopherol at a concentration of 0.4 microM, representing 0.8% of the total tocopherol in the plasma sample. This experiment clearly demonstrates that orally administered alpha-tocopheryl quinone is converted in a low overall yield to alpha-tocopherol in humans. The conversion to alpha-tocopherol of that portion of the quinone dose which was actually absorbed into the blood stream may, however, have been fairly efficient.

Administration, Oral↗