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Biomedical subjects

H Theorell

Publications and source records attributed to H Theorell.

At least 19 recordsLinked to original sources
PubMed1997

Effects of oral supplementation of coenzyme Q10 on 31P-NMR detected skeletal muscle energy metabolism in middle-aged post-polio subjects and normal volunteers.

The effects of oral supplementation of 100 mg coenzyme Q10 (CoQ10) for 6 months on muscle energy metabolism during exercise and recovery were evaluated in middle-aged post-polio (n = 3) and healthy subjects (n = 4) by the use of phosphorus-31 nuclear magnetic resonance spectroscopy. The metabolic response to isometric plantar flexion at 60% of maximal voluntary contraction force (MVC) for 1.5 min was determined in gastrocnemius muscles before, after 3- (3MO) and 6-month (6MO) of CoQ10 supplementation. The MVC of plantar flexion was unchanged following CoQ10 supplementation. The resting Pi/PCr ratio in gastrocnemius muscles of all subjects decreased after 3MO- and 6MO-CoQ10 (P < 0.05). The post-polio individuals showed a progressive decrease in this ratio, while less pronounced changes were observed in the control subjects. Similarly, the post-polio individuals showed a lower Pi/PCr ratio at the end of 60% MVC in both 3MO- and 6MO-CoQ10, whereas no change in the ratio was observed in the control subjects. A less pronounced decrease in muscle pH was observed at the end of 60% MVC in both 3MO- and 6MO-CoQ10 in the post-polio individuals, but not in the control subjects. No systematic difference in end-exercise ATP was observed between the three phases in both groups. The half-time of recovery for PCr decreased in all subjects after 6MO-CoQ10 supplementation (P < 0.05). The results suggest that CoQ10 supplementation affects muscle energy metabolism in post-polio individuals to a greater extent than in control subjects. The mechanism for this effect is not clear, but may involve an effect of CoQ10 on peripheral circulation in the calf muscles, its action in mitochondrial oxidative phosphorylation and/or its antioxidant potential.

Administration, Oral↗
PubMed1993

Ubiquinone and alpha-tocopherol in plasma; means of translocation or depot.

Ubiquinone (UQ) and alpha-tocopherol (AT) are two highly lipophilic antioxidants which can be dissolved only in lipid layers or attached to protein structures. Analyses of both UQ and AT in whole blood and plasma demonstrate identical values, which excludes any significant allocation to blood cells. The lipoidic plasma structures constitute the plasma lipoprotein fractions of high (HDL), low (LDL), and very low (VLDL) density in addition to chylomicrons. This means by definition that blood and plasma UQ and AT values are limited if not related to the lipoidic deposit volume. UQ and AT increase linearly with free cholesterol (FC). FC has therefore been suggested to be a good marker for the deposit volume. The ratios UQ and AT over FC--normalized UQ (N-UQ) and normalized AT (N-AT)--have been computed for inter- and intraindividual comparisons. With a plasma UQ content of 1 microgram/ml (approximately 1 mumol/l) and a plasma volume of 41, UQ makes up about 15% of the total heart content or under 1% of UQ in skeletal muscle. The corresponding value for the total extracellular UQ content is less than 2%. This means that extracellular UQ has no or a very minor role as a UQ depot. The same is true for AT. However, for transportation and allocation determinations of N-UQ and N-AT are relevant. Assuming only a lipoprotein-related transportation, healthy persons have saturated plasma UQ and AT values in only 25% and 10% of the population, respectively. All patient categories studied have been found nonsaturated. VLDL plus LDL constitute some 90% of the UQ deposit volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1992

Plasma ubiquinone, alpha-tocopherol and cholesterol in man.

Plasma ubiquinone, coenzyme Q10 or CoQ10 has been analyzed in plasma together with alpha-tocopherol and free cholesterol in healthy sedentary male subjects (SS), endurance trained male athletes (ET) and male patients with severe ischemic heart disease (IHD). Higher means were found in SS compared to both IHD and ET. Moreover, the ratios CoQ10 and alpha-tocopherol over free cholesterol were higher. In all groups significant relationships were found between the two products of the mevalonate pathway: CoQ10 and cholesterol (r ranged 0.66-0.86, p less than 0.01). The two lipophilic antioxidants, CoQ10 and alpha-tocopherol, were interrelated only in IHD (r = 0.86, p less than 0.001), borderline in SS (r = 0.51, p less than 0.05) but not in ET. It is assumed that plasma free cholesterol reflects the capacity to transport lipids and lipophilic compounds in blood. With metabolic stress and an elevated radical formation as in IHD and ET, the lower CoQ10 and alpha-tocopherol to cholesterol ratios mirror a subsequent toll on the scavenging potential. The difference in LDL levels between IHD and ET and the different storage capacity of CoQ10 and alpha-tocopherol might explain the tight coupling in IHD but not in ET. It is possible that the toll reflects both an intra- and extracellular radical quenching activity. The joint effect of the two lipophilic, extracellular antioxidants CoQ10 and alpha-tocopherol role in protecting e.g. LDL particles from peroxidation is suggested.

Cholesterol↗
PubMed1991

Coenzyme Q10, alpha-tocopherol and free cholesterol in HDL and LDL fractions.

Twenty-three randomly selected plasma samples from apparently healthy, middle aged men were analysed for coenzyme Q10 (CoQ10), alpha-tocopherol (AT) and free cholesterol (FC) in: 1) whole plasma, 2) the HDL lipoprotein fraction after LDL precipitation (VLDL + LDL). CoQ10, AT and FC in plasma averaged 0.69 +/- .11, 6.74 +/- 1.78 micrograms x ml-1 and 0.59 +/- .11 mg x ml-1 and in HDL 0.17, 3.24 micrograms x ml-1 and 0.17 mg x ml-1 or 29, 48 and 29% of plasma values. Amounts of CoQ10 and AT were correlated to that of FC in all pools. The amount of HDL-CoQ10 but not of HDL-AT fell, with the HDL-FC expressed as the fraction of plasma FC. In all pools, N-AT versus AT initially increased and then levelled off, indicating saturation like conditions in contrast to CoQ10. Thus, CoQ10 and AT are differently allocated in HDL and LDL. This might have a bearing both on the suggested lipoprotein protection against peroxidation by these two antioxidants, but also on the distribution and allocation in different organs of CoQ10 and AT by HDL and LDL transportation.

Cholesterol↗
PubMed1986

Lowered glutathione-peroxidase activity in asthmatic patients with food and aspirin intolerance.

In analogy with findings from animal experiments, people with low glutathione-peroxidase (GSH-Px) activity could be expected to have altered sensitivities to effects of drugs, chemicals and possibly food. We have investigated GSH-Px activity in 12 patients with intrinsic asthma and food and aspirin intolerance. Ten of the 12 patients had very low or low GSH-Px activity and the frequency of low GSH-Px activity in this group was statistically significant (P less than 0.001) compared with the control material of age- and sex-matched healthy individuals. Our finding of lowered GSH-Px activity in patients with aspirin intolerance may indicate the involvement of hitherto unknown mechanisms in the pathogenesis of asthmatic disorders.

Arachidonic Acid↗
PubMed1983

Effects of dietary protein-tryptophan restriction upon 5-HT uptake by platelets and clinical symptoms in migraine-like headache.

Ten women with recurrent migraine-like headache, flush, urticaria and itching excoriations were put on a protein/tryptophan reduced diet. The 5-HT uptake kinetics in platelets, the frequency of headache attacks and skin symptoms were recorded. On customary food the 5-HT uptake kinetics were severely disturbed. On diet, the platelet 5-HT uptake was normalized and, in parallel, the migraine-like symptoms and skin manifestations were reduced. The parallel between the improvement in active 5-HT uptake by platelets and clinical symptoms during dietary protein/tryptophan restriction supports the idea that impairment of the 5-HT uptake in platelets is a contributory factor in the pathogenesis of migraine-like headache and other 5-HT related symptoms.

Adult↗
PubMed1982

Defective serotonin (5-HT) transport mechanism in platelets from patients with endogenous and allergic asthma.

The kinetics of the 5-HT-uptake by platelets in platelet-rich plasma (PRP) and PRP diluted with autologous platelet-poor plasma (PRP/PPP) were determined in normal subjects, patients with asymptomatic exogenous asthma and those with symptomatic endogenous asthma. In normal subjects the 5-HT-uptake by platelets strictly obeyed Michaelis-Menten's kinetics. In patients with asymptomatic exogenous asthma, the active 5-HT-transport was moderately distorted in PRP and severely altered in PRP/PPP. Patients with symptomatic endogenous asthma exhibited already in PRP a dramatic transport disturbance. The alteration of the active 5-HT-transport was characterized by increasing uptake inhibition by rising 5-HT concentrations in plasma. This phenomenon could be due to changes in the platelet environment, defects in the platelet membrane or intrinsic platelet disorders. It is concluded that asthmatics have genetically or later acquired platelet disorder, which is more clearly observed in patients with symptomatic endogenous asthma than in those with asymptomatic exogenous asthma.

Adolescent↗
PubMed1979

Chemical relaxation studies on the horse liver alcohol dehydrogenase system.

Chemical relaxation studies on the system horse liver alcohol dehydrogenase, nicotinamide adenine dinucleotide, and ethanol were conducted observing fluorescence changes between 400 and 500 nm. Temperature-jump experiments were performed at pH 6.5, 7.0, 8.0, and 9.0; concentration-jump experiments at pH 9.0. The reciprocal of the slowest relaxation time was found to be linearly dependent upon the enzyme concentration for relatively low enzyme concentrations, as predicted earlier. Use of the wide pH-range necessitated expression of the four apparent dissociation constants of the catalytic reaction cycle in terms of pH-independent constants. The system was described in terms of only one (or two) catalysis-linked protons not associated with the electron transfer. Protonic steps in a buffered system are in rapid equilibrium, too fast to be measured with the equipment available. Assuming only two of the four bimolecular reaction steps in the four-step cycle are fast compared to the remaining two, six cases may be considered with six expressions for the reciprocal of the slowest relaxation time. Comparison with the experimental data revealed that the bimolecular reaction steps governing the slowest relaxation time change with pH. Above the effective time resolution of the temperature-lump instrument with fluorescence detection (0.1 msec) only one other relaxation time was detectable and only at pH 9. This relaxation time, found to be independent of the concentration of all reactants within experimental error (r = 10 +/- 5 msec), is most likely due to an interconversion among ternary complexes.

Alcohol Oxidoreductases↗
PubMed1976

Demonstration of reactivity to airborne and food allergens in cutaneous vasculitis by variations in fibrinopeptide A and other blood coagulation, fibrinolysis and complement parameters.

In a 32-year-old woman and a 40-year-old man with cutaneous vasculitis, etiological allergic responses to foods and airborne allergens were found. During provocation tests, observations were made on blood levels of fibrinopeptide A(FPA) and coagulation factors, fibrinogen degradation products (FDP) and serum complement components. Skin biopsies were taken for microscopic and immunofluorescence analysis. In case 1, anaphylactoid allergy to milk and reaginic and anaphylactoid hypersensitivity to grass pollens were found. Dermal provocations with grass pollens gave arthralgia, hematomas, serum C3 fluctuation, factor VII reduction and fibrinolysis. During peroral milk challenge, transient increases in FPA and FDP levels were observed before symptoms appeared. In case 2, anaphylactoid hypersensitivity responses to bacteria, animal danders, foods and pollens were found. Two inhalations with sheep-wool extract resulted in a typical skin eruption. The first also gave an early reduction of C3 and then FPA liberation. Nasal birch-pollen test gave an increase of FPA in the latent period and then typical nodules. At least no low molecular weight FDP were detected during provocations. In patients with vasculitis reactions to exogenous allergens, FPA and FDP estimations after provocations may discriminate harmful from innocuous allergens and reveal individual response patterns in coagulation and fibrinolysis systems.

Adult↗
PubMed1976

Dissociation and rate constants of some human liver alcohol dehydrogenase isoenzymes.

ADH from human liver forms binary complexes with NADH, associated with a blue shift of the peak of the fluorescence emission of NADH. The wavelength shift is the same for all isoenzymes but the accompanying intensification of the fluorescence is different. The fluorescence is further increased by the formation of the very tight ternary enzyme-NADH-isobutyramide complexes. These properties are similar to those for the horse liver ADH, as well as the molecular weight of E=40 000 per active site of the dimer molecule (EE). "Stopped-flow" determined velocity constants (ER in equilibrium E+R) were found to be in good agreement with ethanol activity constants previously determined by activity measurement, confirming the validity of the ordered ternary complex mechanism also for the human ADH. No single isoenzyme activity as high as that reported by Mourad and Woronick or Drum has been found.

Alcohol Oxidoreductases↗
PubMed1975

Steroid oxidoreductase activity of alcohol dehydrogenases from horse, rat, and human liver.

Alcohol dehydrogenase from horse (isoenzyme SS and ES, but not EE), rat and human liver were found to catalyze the NAD-dependent oxidation of 3beta-hydroxy groups in 5alpha- and 5beta-steroids of the C19, C21, and C24 series. The enzymes from horse and rat liver were more active on 5beta-than on 5alpha-steroids. This difference was most marked with the enzyme from rat liver, especially with 3beta-hydroxyandrostan-17-ones and 3beta-hydroxypregnan-20-ones as substrates. The Km of isoenzyme ES from horse liver was lower for 3beta-hydroxy-5alpha-cholanoic acid (0.4 muM) than for 3beta-hydroxy-5beta-cholanoic acid (0.9 muM). 3alpha-Hydroxysteroids were not substrates for the enzymes from horse and rat liver. Human liver alcohol dehydrogenase had low affinity for 3beta-hydroxy-5alpha (and 5beta)-cholanoic acids, but oxidation could be clearly demonstrated by gas chromatographic analysis of the products.

Alcohol Oxidoreductases↗
PubMed1975

Chemical relaxation studies on the system liver alcohol dehydrogenase, NADH and imidazole.

Several years ago, Theorell and Czerlinski conducted experiments on the system of horse liver alcohol dehydrogenase, reduced nicotinamide adenine dinucleotide and imidazole, using the first version of the temperature jump apparatus with detection of changes in fluorescence. These early experiments were repeated with improved instrumentation and confirmed the early experiments in general terms. However, the improved detection system allowed to measure a slight concentration dependence of the relaxation time of around 3 ms. Furthermore, the chemical relaxation time was smaller than the one determined earlier (by factor 2). The data were evaluated much more rigorously than before, allowing an appropriate interpretation of the results. The observed relaxation time is largely due to rate constants in an interconversion of ternary complexes, which are faster than three (of the four) dissociation rate constants, determined previously by Theorell and McKinley-McKee.1,2 This fact contributed to earlier difficulties of finding any concentration dependence. However, the binding of imidazole to the binary enzyme-coenzyme complex can be made to couple kinetically into the interconversion rate of the two ternary complexes. The observed signal derives largely from the ternary complex(es). A substantial fluorescence signal change is associated with the observed relaxation process, suggesting a relocation of the imidazole in reference to the nicotinamide moiety of the bound coenzyme. Nine models are considered with two types of coupling of pre-equilibria (none-all). Quantitative evaluations favor the model with two ternary complexes connected by an interconversion outside the four-step (bimolecular) cycle. The ternary complex outside the cycle has much higher fluorescence yield than the one inside. The interconversion equilibrium is near unity for imidazole. If it would be shifted very much to the side of the "dead-end" complex (as in isobutyramide?!), stimulating action could not take place.

Alcohol Oxidoreductases↗