Convenient synthesis of 18-hydroxylated cortisol and prednisolone.

18,20-Epoxy-11 beta,17 alpha,20 beta,21-tetrahydroxypregn-4-en-3-one was synthesized by the application of hypoiodite reaction to the cortisol acetonide. The intermediary 18-iodo derivative was converted to the 11-oxo steroid by chromic acid prior to silver ion-assisted solvolysis. Removal of the protective group with hydrochloric acid was finally carried out to give the desired 11 beta,17 alpha,18,21-tetrahydroxypregn-4-ene-3,20-dione as the hemiacetal form. 18,20-Epoxy-11 beta-17 alpha,20 beta,21- tetrahydroxypregna-1,4-dien-3-one was also prepared from prednisolone through a similar reaction sequence.     

Kinetics of hydroperoxide degradation by NADP-glutathione system in mitochondria

Hydroperoxide decomposition by the NADP-glutathione system in rat liver mitochondria was analyzed. Mitochondria were found to contain high concentrations of the reduced form of glutathione (GSH) (4.32 +/- 0.50 nmol/mg) and NADPH (4.74 +/- 0.64 nmol/mg), and high activities of glutathione peroxidase and reductase. In the initial phase of the reaction, the rate of hydroperoxide decomposition was proportional to both the GSH level and the activity of GSH peroxidase. However, in the later steady state, the step of NADP reduction was rate-limiting, and the overall reaction rate was independent of the initial concentration of GSH, and activities of glutathione peroxidase and reductase. Some GSH was released from mitochondria during incubation, but the rate of the decomposition could be simply expressed as kappa [GSH]/2, where kappa is the first-order rate constant of the peroxidase and [GSH] is the intramitochondrial level of GSH in the steady state. The rate of the reaction in the steady state was also dependent on the NADPH level, its reciprocal being linearly correlated with [NADPH]-1. The rate of decomposition of hydroperoxide was influenced by the respiratory state. During state 3 respiration, the rate was greatly depressed, but was still considered to exceed by far the rate of physiological generation of hydroperoxide.     

Transport of glutathione across the mitochondrial membranes

Transport of glutathione (GSH) into mitochondria was observed when mitochondria in state 4 respiration were incubated with high concentrations of GSH. This transport was suppressed by antimycin A or dicyclohexyl-carbodiimide, or in state 3 respiration. Upon dissipation of the proton gradient by a proton ionophore, mitochondrial GSH was released into the medium. GSH moved freely across the proton-permeated mitochondrial membrane, its movement depending only on the GSH gradient across the inner membrane. These results indicate that there is a transport system for GSH in the mitochondrial membrane, and that a proton gradient is necessary to maintain GSH in the matrix, and to transport GSH into mitochondria.     

Cerebro-costo-mandibular syndrome

Summary A 7-month-old boy with the cerebro-costomandibular syndrome is presented. This is the first case report in an Oriental population.15 reported cases in the literature are reviewed.     

The “happy puppet” syndrome in two siblings

Summary Disomic and trisomic cells of a patient with Down syndrome mosaic were used to study the effect of the additional chromosome 21 against an identical genetic background. The frequency of Ag staining and the participation in satellite associations were determined for each pair of acrocentric chromosomes. The additional chromosome 21 of the trisomic cells and its homologues proved to be regularly Ag positive. Therefore the trisomic cells showed more Ag positive chromosomes and more satellite associations per cell than the diploid cells. Thus, no compensation for the additional rRNA-gene dose could be found in the cells of the trisomic line.     

Co-pigmentation and the color change with age in petals ofFuchsia hybrida

Pure or genuine malvin was isolated fromFuchsia petals for the first time and characterized as the malvin anhydro-base. The conditions for the co-pigmentation were examinedin vitro with regard to anthocyanin, co-pigment and pH, and the co-pigmentation occurred as the result of interaction between anthocyanin and co-pigment without any participation of metallic elements. The blue-violet color of youngFuchsia petals appeared at pH 4.8 in the 1∶0.6 molar ratio of anthocyanin to co-pigments. The color change from blue-violet in young petals to purple-red in old ones was caused by co-pigmentation and the pH change from 4.8 to 4.2. The decrease of pH in the old petals was due to the increase of organic acids such as aspartic, malic and tartaric acids.     

Studies on metabolic role of 5′-methylthioadenosine in Ochromonas malhamensis and other microorganisms

Several compounds containing a thiomethyl group were found to replace vitamin B₁₂ in a protozoan, Ochromonas malhamensis. The order of the effectiveness was as follows: 5-methylthioadenosine > S-adenosylmethionine > 5-methylthioribose > L-methionine. A similar order was obtained with respect to the permeability of these compounds into the protozoan cells, except for S-adenosylmethionine. 5-Methylthioadenosine and 5-methylthioribose as well as l-methionine markedly increased the intracellular content of l-methionine. The level of S-adenosylmethionine was also increased by them, but to a lesser degree. The thiomethyl group of the compounds was established to be incorporated into S-adenosylmethionine. The metabolic fate of the thiomethyl group of 5-methylthioadenosine cannot be distinguished from that of l-methionine. A high activity of 5-methylthioadenosine nucleosidase was detected in the cell-free extracts of the protozoan. These results strongly suggest that 5-methylthioadenosine would be metabolized to l-methionine via 5-methylthioribose and then the l-methionine would be converted to S-adenosylmethionine. Like l-methionine and vitamin B₁₂, 5-methylthioadenosine and 5-methylthioribose may play an important role in maintenance of the C-1 pool in Ochromonas malhamensis.Neither 5-methylthioadenosine nor 5-methylthioribose replaced vitamin B₁₂ in some vitamin B₁₂-requiring bacteria. This result is consistent with the fact that neither compounds was significantly taken up by these bacteria.Abbreviations MTA 5-methylthioadenosine - AdoMet S-adenosylmethionine - MTR 5-methylthioribose - TCA trichloroacetic acid Paper II in the series. The first paper of the series has been published (Sugimoto and Fukui, 1974)     

ABCG2 expression and uric acid metabolism of the intestine in hyperuricemia model rat

Abstract

To elucidate roles of the intestine in uric acid (UA) metabolism, we examined ABCG2 expression, tissue UA content and xanthine oxidoreductase (XOR) activity in different intestinal segments. Male SD rats were assigned to control group or oxonic acid-induced hyperuricemia (HUA) group. In control rats, ABCG2 was present both in villi and crypts in each segment. Tissue UA content and XOR activity were relatively high in duodenum and jejunum. However, in HUA rats, tissue UA content was significantly elevated in the ileum, whereas it remained unaltered in other segments. Moreover, ABCG2 expression in the HUA group was upregulated both in the villi and crypts of the ileum. These data indicate that the ileum may play an important role in the extra-renal UA excretion.