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Biomedical subjects

R G Matthews

Publications and source records attributed to R G Matthews.

At least 109 records · Page 6Linked to original sources

ECG effects of aerobic dance: a study of five exercise-conditioned young women.

Monitoring of the heart rate of five healthy well-conditioned women during an aerobic dance routine showed that maximum rates were within acceptable limits for exercise tachycardia except in one subject, who had paroxysmal supraventricular tachycardia that subsequently converted to sinus tachycardia. Thus, although aerobic dance seems a benign form of exercise, it can be intense enough to trigger dysrhythmias. Before recommending or approving it for any patient, the physician should take into consideration the person's age, health, and physical fitness level.

Adult↗

Characterization of the dihydropterin reductase activity of pig liver methylenetetrahydrofolate reductase.

Pig liver methylenetetrahydrofolate reductase catalyzes the reduction of quinonoid dihydropterins in vitro. Either NADPH or methyltetrahydrofolate can serve as the electron donor. Methylenetetrahydrofolate reductase can also suppor phenylalanine hydroxylation in vitro by regeneration of the tetrahydropterin cofactor. These results lend support to the proposal that reduction of methylenetetrahydrofolate proceeds by tautomerization of the 5-iminium cation to form quinonoid 5-methyldihydrofolate, which is then reduced to methyltetrahydrofolate (Matthews, R. G., and Haywood, B. J. (1979) Biochemistry 18, 4845-4851). Under Vmax conditions, the turnover numbers for the NADPH-linked reductions of the quinonoid forms of 6,7-dimethyldihydropterin, dihydrobiopterin, and dihydrofolate are all about the same as that for the reduction of methylenetetrahydrofolate. The Km values for racemic mixtures of the same quinonoid acceptors are 40, 30, and 20 microM, respectively, while the Km for (6R,S)methylenetetrahydrofolate is 20 microM at pH 7.2 in phosphate buffer. The reduction of quinonoid dihydropterins is inhibited by adenosylmethionine and dihydropteroylhexaglutamate, which are known to modulate methylenetretrahydrofolate reductase activity.

Animals↗

Interactions of pig liver methylenetetrahydrofolate reductase with methylenetetrahydropteroylpolyglutamate substrates and with dihydropteroylpolyglutamate inhibitors.

Dihydrofolate and dihydropteroylpolyglutamates inhibit pig liver methylenetetrahydrofolate reductase. In all cases the inhibition is linearly competitive with respect to methylenetetrahydrofolate. The Ki values decrease with each additional glutamyl residue from one to six, from a value of 6.5 microM for dihydrofolate to 0.013 microM for dihydropteroylhexaglutamate. Dihydropteroylheptaglutamate has a Ki of 0.065 microM. These data indicate a free energy of binding of approximately 0.75 kcal/mol for each of the five terminal glutamyl residues in dihydropteroylhexaglutamate. Methylenetetrahydropteroylpolyglutamates are substrates for the enzyme, and the increased free energy of binding is reflected in increased values for Vmax/Km with polyglutamate substrates. Vmax is increased 1.76-fold on going from the mono- to the diglutamate substrate; additional glutamyl residues lead to decreases in Km values for methylenetetrahydropteroylpolyglutamates. Our results suggest that the in vivo activity of methylenetetrahydrofolate reductase may also be sensitive to fluctuations in the ratio of methylenetetrahydropteroylpolyglutamates to dihydropteroylpolyglutamates and that this ratio may be important in determining the relative fluxes of methylenetetrahydropteroylpolyglutamates into the pathways leading to thymidylate biosynthesis and methionine regeneration.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

Ovulation and the movement of the conceptus in the first 35 days of pregnancy in thoroughbred mares.

Data from 937 Thoroughbred mares, when analysed as a single population, showed no significant difference between the activity of the right and left ovaries and the frequency of location of 35-day pregnancies in the right and left uterine horns. Nor were any differences shown when the data were analysed in years or sire groups. However, significantly more ovulations occurred in the right ovary in September and December and in the left ovary in October and November. Whereas the left and right ovulations were equal in lactating and dry mares, there was a highly significant increase in the number of pregnancies in the right uterine horn in dry mares and in the left uterine horn in lactating mares.

Animals↗

Measurement of the oxidation-reduction potentials for two-electron and four-electron reduction of lipoamide dehydrogenase from pig heart.

The oxidation-reduction potential, E2, for the couple oxidized lipoamide dehydrogenase/2-electron reduced lipoamide dehydrogenase has been determined by measurement of equilibria of these enzyme species with lipoamide and dihydrolipoamide or with oxidized and reduced azine dyes. E2 is -0.280 V at pH 7, and deltaE2/deltapH is -0.06 V in the pH range 5.5 to 7.6. Values for E1, the oxidation-reduction potential for the couple 2-electron reduced enzyme/4-electron reduced enzyme, were obtained from measurements of the extent of dismutation of 2-electron reduced enzyme to form mixtures containing oxidized and 4-electron reduced enzyme. E1 is -0.346 V at pH 7, and deltaE1/deltapH is -0.06 V in the pH range 5.7 to 7.6. Spectra of oxidized enzyme and 4-electron reduced enzyme do not show variations with pH over this range, but the spectrum of the 2-electron reduced enzyme is pH-dependent, with the molar extinction at 530 nm changing from 3250 M-1 cm-1 at pH 8 to 2050 M-1 cm-1 at pH 5.2. The pH-dependent changes which are observed in the absorption properties of the 2-electron reduced enzyme are consistent with the disappearance of a charge transfer complex between an amino acid side chain and the oxidized flavin at the lower pH values, with the apparent pK of the side chain at pH 5. It has been suggested that the 530 nm absorbance of 2-electron reduced enzyme is due to a charge transfer complex between thiolate anion and oxidized flavin, and we propose that the thiolate anion is stabilized by interaction with a protonated base. The thermodynamic data predict that the amount of 4-electron reduced enzyme formed when the enzyme is reduced by excess NADH will be pH-dependent, with the greatest amounts seen at low pH values. These data support earlier evidence (Matthews, R.G., Wilkinson, K.D., Ballou, D,P., and Williams, C.H., Jr. (1976) in Flavins and Flavoproteins (Singer, T.P., ed) pp. 464-472; Elsevier Scientific Publishing Co., Amsterdam) that the role of NAD+ in the NADH-lipoamide reductase reaction catalyzed by lipoamide dehydrogenase is to prevent accumulation of inactive 4-electron reduced enzyme by simple reversal of the reduction of 2-electron reduced enzyme by NADH.

Animals↗

Identification of p-hydroxybenzaldehyde as the ligand in the green form of old yellow enzyme.

We have previously reported the isolation of old yellow enzyme complexed with a ligand of low molecular weight which imparts a distinctive charge-transfer absorption to the enzyme, making it green in color (Matthews, R. G., and Massey, V. (1969) J. Biol. Chem. 244, 1779-1789). This ligand has now been identified as p-hydroxybenzaldehyde by removal from the enzyme and characterization of its optical spectrum and subsequent mass spectral analysis. Similar compounds which are also bound to old yellow enzyme have been isolated from yeast extract and identified. These compounds give rise to complexes with old yellow enzyme which are characterized by broad long wavelength absorption bands, and they lead to inhibition of the NADPH-O2 oxidoreductase activity catalyzed by old yellow enzyme.

Benzaldehydes↗

Reversibility of left ventricular asynergy by nitroglycerin in coronary artery disease.

To evaluate the potential reversibility of left ventricular asynergy in patients with coronary artery disease, pre- and postnitroglycerin left ventriculography was performed in 32 subjects. In four other subjects left ventriculography was repeated without intervention of nitroglycerin. Changes in ejection fraction and percentage of systolic shortening of three minor axes from the first to the second angiogram were then calculated. Changes were not significant for the myocardial infarction group or for the control group without the intervention of nitroglycerin. Normal left ventricles showed small but significant changes (p less than 0.05). Patients with coronary artery disease but without previous myocardial infarction who demonstrated asynergy in their first angiogram showed three types of response: (1) no significant change (p less than 0.05)-irreversible asynergy; (2) significant change (p less than 0.025) with residual dysfunction-partially reversible asynergy; (3) significant change (p less than 0.001) without residual dysfunction-completely reversible asynergy. It is concluded that postnitroglycerin ventriculography is useful in assessing the reversibility of left ventricular asynergy in patients with coronary artery disease.

Adult↗

Mechanism of normal splitting of the second heart sound.

The mode of inspiratory augmentation (1A) of the A2-P2 interval was investigated in seven normal volunteers (group 1) and six patients with pulmonary hypertension of diverse etiology (group 2) using catheter-tip micromanometers. In group 1 subjects, inspiratory widening of this interval was found to average 27.2 msec, of which 7.6 plus or minus 2.7 msec (1 sd) or 27 plus or minus 7% was due to a decrease in the Q-A2 interval. The major contribution of Q-P2 interval prolongation was divided into two components: a) Q-O was measured from the onset of the QRS to the onset of the rapid descent of the right ventricular (RV) negative dp/dt, which was felt to reflect the duration of RV electromechanical systole, b) O-P2 or Q-P2 - Q-O. Increase in the Q-O interval accounted for only 7.7 plus or minus 5.0 msec or 28 plus or minus 12% of the total IA. The major single component of IA was the increase in O-P2 which averaged 11.9 plus or minus 3.0 msec. Five of six group 2 patients demonstrated significant respiratory change in Q-P2 intervals. In contrast to group 1 subjects, however, this was accomplished primarily via increases in the duration of RV electromechanical systole. The O-P2 interval is felt to primarily reflect the impedance characteristics of the pulmonary vascular bed. It is concluded that physiologic splitting of the second heart sound in normal subjects is most probably due to an inspiratory decrease in impedance of the pulmonary bed rather than the traditional explanation of prolongation of RV systole secondary to an increase in venous return. When the normal impedance characteristics of this bed are lost, as in pulmonary hypertension, IA must occur primarily via increases in the duration of RV systole. The inspiratory delay from the conclusion of RV systole to the occurrence of P2 is attributed to the inertiance of the RV stroke mass.

Adolescent↗