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Biomedical subjects

I Yamazaki

Publications and source records attributed to I Yamazaki.

At least 163 records · Page 9Linked to original sources
PubMed1979

Anti-androgen TSAA-291. III. Hormonal spectra of anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) and its derivatives.

For the purpose of obtaining hormonal spectra of anti-androgen TSAA-291 and its derivatives, a variety of endocrine characteristics were studied. (1) Androgenic and anabolic activity : Subcutaneous administration of anti-androgen TSAA-291 and its acetate, TSAA-328, to the immature orchiectomized rat resulted in significant weight increase of the levator ani but in only a nominal response of seminal vesicles and prostates even at a large daily dose of 9.6 mg. The resultant anabolic/androgenic ratio was estimated to be extremely high. (2) Oestrogenic activity : Uterine weight in response to these anti-androgens were sluggishly dose-dependent, and the maximal plateau response remained considerably lower than that induced by oestradiol-17 beta. The oestrogenic activity of these anti-androgens was estimated to be 1/200 000 or less as that of oestradiol-17 beta. A single subcutaneous dose of 100 mg of TSAA-291 or its caproate, TSAA-330, did not induce the vaginal cornification in the adult ovariectomized rat. (3) Anti-oestrogenic activity : Antagonistic effect of these anti-androgenic compounds on the uterine weight response to oestradiol-17 beta was found in the immature ovariectomized rat. A single subcutaneous dose of 100 mg of TSAA-291 or TSAA-330 also induced the antagonism against the cornification caused by daily treatments with 1 microgram oestrone in the adult ovariectomized rat. (4) Progestational activity : These anti-androgenic compounds proved to be less active than progesterone in the McPhail's test. (5) Anti-inflammatory activity : Daily subcutaneous dose of 20 mg of TSAA-291 for 6 days did not significantly depress the weight of granuloma developed around the cotton-pellet implanted in the young male rat. TSAA-291 did not affect the anti-inflammatory action of 1/6 mg of prednisolone phosphate. Combination of both agents seemed to be effective in enhancing the anti-androgenic action of TSAA-291, whereas prednisolone phosphate alone rather increased the weight of the accessory sex organs. (6) Liver glycogen deposition activity : Daily intramuscular doses up to 38.4 mg of TSAA-291 for 5 days did not increase the liver glycogen level in the adrenalectomized rat.

Androgen Antagonists↗
PubMed1979

Anti-androgen TSAA-291. IV. Effects of the anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the secretion of gonadotrophins.

Effects of the anti-androgen TSAA-291 on the gonadotrophin secretion were studied. (1) A single subcutaneous or oral administration of TSAA-291 and its caproate induced the ovulation in the proestrous rat of which the spontaneous ovulation was blocked by the treatment with chlorpromazine. (2) A single subcutaneous administration of TSAA-291 at 2.4 mg/kg to the adult male rat induced only a slight elevation in the serum LH and FSH levels at 30 min after the administration. Successive intramuscular administrations of TSAA-291 to the adult male rat for 2 or 4 weeks resulted in significant decreases in the serum LH and FSH levels at high dose levels. A dose-dependent decrease in the serum LH level but not FSH level was observed in the orchiectomized rat. (3) Successive intramuscular administrations of TSAA-291 at high dose levels to the male rat suppressed the plasma testosterone level in the testicular venous blood and general circulation.

Administration, Oral↗
PubMed1978

Kinetic analysis of the acid-alkaline conversion of horseradish peroxidases.

The nature of the acid-alkaline conversion of horseradish peroxidases was studied by measuring four rate constants in reactions, E + H+ (k1) in equilibrium (k2) EH+ and E + H2O (k3) in equilibrium (k4) EH+ + OH-, where EH+ and E denote the acid and alkaline forms of the enzymes. The values of k1, (k2 + k3), and k4 were obtained by measuring the relaxation rates of the acid leads to alkaline and alkaline leads to acid conversions by means of th pH jump method with a stopped-flow apparatus. The value of k3 could also be obtained by measuring the rate of reactions between hydrogen peroxide and peroxidases at alkaline pH. The measurements were conducted with four peroxidases having different pKa values: peroxidase A )pKa = 9.3), peroxidase C (pKa = 11.1), diacetyldeuteroperoxidase A (pKa = 7.7), and diacetyldeuteroperoxidase C (pKa = 9.1). The value of k1 was about 10(10) M-1 s-1 in the reaction of the four enzymes while k4 was quite different between the enzymes. The pKa was determined by k3 and k4 for the natural peroxidases and by k1 and k2 for the diacetyldeuteroperoxidases. The mechanism of the acid-alkaline conversion was discussed in comparison with that of metmyoglobin.

Acetylation↗
PubMed1978

Analysis of acid-base properties of peroxidase and myoglobin.

Two heme-linked groups of horseradish peroxidases, characterized by pKa = 5.8 (isoenzyme A) and 7.3 (isoenzyme C), are believed to be distal amino acid residues and, judging by their acid-base properties in various derivatives, influence the functions of these isoenzymes. In contrast, in myoglobin ionization of the distal histidine does not influence its reactivity. Accordingly, we conclude that the interaction of the distal base with a 6th ligand is weak in myoglobin but very strong in peroxidases.

Hemoglobins↗
PubMed1977

Analysis and computer simulation of aerobic oxidation of reduced nicotinamide adenine dinucleotide catalyzed by horseradish peroxidase.

Under suitable experimental conditions the aerobic oxidation of NADH catalyzed by horseradish peroxidase occurred in four characteristic phases: initial burst, induction phase, steady state, and termination. A trace amount of H2O2 present in the NADH solution brought about initial burst in the formation of oxyperoxidase. About 2 mol of oxyperoxidase was formed per mol of H2O2. When a considerable amount of the ferric enzyme still remained, the initial burst was followed by an induction phase. In this phase the rate of oxyperoxidase formation from the ferric enzyme increased with the decrease of the ferric enzyme and an approximately exponential increase of oxyperoxidase was observed. A rapid oxidation of NADH suddenly began at the end of the induction phase and the oxidation continued at a relatively constant rate. In the steady state, oxygen was consumed and H2O2 accumulated. A drastic terminating reaction suddenly set in when the oxygen concentration decreased under a certain level. During the reaction, H2O2 disappeared accompanying an accelerated oxidation of NADH and the enzyme returned to the ferric form after a transient increase of peroxidase compound II. Time courses of NADH oxidation, O2 consumption, H2O2 accumulation, and formation of enzyme intermediates could be simulated with an electronic computer using 11 elementary reactions and 9 rate equations. The results were also discussed in relation to the mechanism for oscillatory responses of the reaction that appeared in an open system with a continuous supply of oxygen.

Computers↗
PubMed1977

The carbon monoxide-binding hemoprotein reducible by hydrogen peroxide in microsomal fractions of pea seeds.

There exist at least two kinds of CO-binding hemoproteins in microsomal fractions of germinating pea (Pisum sativum) seeds. One of them is cytochrome P-450 and the other is also a protoheme protein (judged from its pyridine hemochrome spectrum), which is not hitherto reported. The content of the new hemoprotein is much higher than that of cytochrome P-450 in the early stage of germination. During germination the former decreases and the latter increases. The new hemoprotein is not appreciably reduced by sodium dithionite alone within a few minutes, but, it is easily reduced by dithionite in the presence of methyl viologen and also by hydrogen peroxide when CO is present. The addition of hydrogen peroxide to pea microsomes in the absence of CO causes destruction of the hemoprotein and also decolorization of endogenous carotenoid. Destruction of these components is brought about by organic hydroperoxides independently of the presence of CO. In the presence of hydroxylamine, the addition of hydroperoxides to the microsomes results in the formation of an absorption spectrum similar to the spectra of ferrous-NO complexes of protoheme proteins. When N,N-dimethyl p-phenylenediamine is present, the reaction of pea microsomes with hydroperoxides gives a spectrum similar to that of the ferryl form of myoglobin. The reactions of the hemoprotein with hydroperoxides are inhibited by alpha,alpha'-dipyridyl and aniline, with which pea microsomes form binding spectra. The microsomes form a rather stable difference spectrum with hydroxylamine. However, the hemoprotein is destroyed when hydroxylamine is added to the microsomes in the reduced state.

Carbon Monoxide↗
PubMed1976

Mechanisms of electron transfer from sulfite to horseradish peroxidase-hydroperoxide compounds.

Using a rapid-scan spectrophotometer equipped with a stopped-flow apparatus, reactions of sulfite with compounds I and II of two horseradish peroxidase isoenzymes A and C were investigated. The direct two-electron reduction of peroxidase compound I by sulfite occurred at acidic pH but the mechanism gradually changed to the two-step reduction with the intermediate formation of compound II as the pH increased. The pH at which the one- and two-electron changes occurred at the same speed was 4.5 for peroxidase A and 7.7 for peroxidase C. A new peroxidase intermediate was found in the reaction between peroxidase compound II and sulfite. The sulfite compound showed a characteristic absorption band at 850 nm and the optical spectrum was similar to that of isoporphyrins but was quite different from that of sulfhemoproteins. The rate (k) of conversion from the sulfite-compound II complex to the sulfite compound was proportional to the concentration of H+ and the log k vs. pH plot for peroxidase A moved to the acidic side by 1.1 pH unit from that for peroxidase C.

Electron Transport↗
PubMed1976

Heme-linked proton dissociation of carbon monoxide complexes of myoglobin and peroxidase.

It was found from spectrophotometric titration and proton balance measurement that the pKa value of a heme-linked protonation group of horseradish ferro-peroxidase C (donor:H2O2 oxidoreductase, EC 1.11.1.7) shifted from 7.25 to 8.25 upon combination with CO. The spectrophotometric titration experiment with myoglobin also revealed the presence of a heme-linked protonation group, the pKa value being 5.57 in myoglobin and 5.67 in the CO-myoglobin complex. It was concluded that the distinct shift of the pKa value in the case of peroxidase was attributable to the presence of a hydrogen bond between the sixth ligand and the distal base. The difference in the strength of such hydrogen bonding between peroxidase and myoglobin was discussed.

Animals↗
PubMed1976

Comparison of function of the distal base between myoglobin and peroxidase.

The heme-linked protonation of a ferrous horseradish peroxidase is assigned to a distal amino acid residue. The conclusion is drawn from analyses of reactions that involve the protonation. Unfortunately it is difficult to apply it to the myoglobin case because no reaction has been found which is coupled with the protonation of the distal histidine. It is therefore of special interest to note that the pK value of 5.7 has been assigned to the distal histidine of metmyoglobin from binding kinetics with ligands20). It is well known that the reaction with hydrogen peroxide is quite different for the two types of hemoproteins. The distal base may be associated with the stabilization of the primary compound with hydrogen peroxide and also another amino acid residue may serve as a nucleophile for the stabilization of the pi-cation radical of porphyrin in the case if peroxidases. Numerous papers have dealt with heme substitution, heme linked protonation and reactions of hemoproteins related to the present subject. In this short paper, however, the discussion has mostly centered around the data obtained recently in our laboratory.

Binding Sites↗