^<57>Co-labeled hydroxocobalamin (OH-B_<12>) and ^<57>Co- or ^<60>Co-cyanocobalamin (CN-B_<12>) were injected to rats by subcutaneous and intravenous routes and tissue distribution and excretion of radioactivity were measured. It was found : 1) OH-B_<12> was taken up to a greater extent than CN-B_<12>, particularly by the liver, kidney and pancreas. 2) The highest uptake occurred in the kidney which was not directly related to urinary excretion. 3) Unlike other organs, the liver radioactivity increased for several days after administration. 4) The excretion of OH-B_<12> was similar to that of CN-B_<12>, the feces being the major excretory route for physiological doses. The urinary excretion increased with the dose given and less OH-B_<12> was lost by this route than CN-B_<12>.

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Hydroxocobalamin (OH-B_<12>) and cyanocobalamin (CN-B_<12>) both labeled with ^<57>Co were compared with respect to binding by serum proteins and retention in blood following intravenous administration in rats. There was no difference in blood retention following injection of physiological doses, but disappearance of OH-B_<12> from blood was retarded compared with CN-B_<12> when given in supraphysiological doses. More OH-B_<12> was bound to serum as determined by dialysis method when its amount to be mixed with serum was increased, whereas no such increase ion binding occurred in CN-B_<12> under the same condition. There was practically no difference between human and rat sera in behavior toward these analogues.

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Thiamine phenylhydrazone (N-(1-methyl-2-phenylhydrazono-4-hydroxybutyl)-N-[(2-methyl-4-amino-5-pyrimidinyl)-methyl]-formamide) (I) was shown to be inhibitory to the growth of Lactobacillus fermenti 36 and Kloeckera apiculata IFO 0630. The growth-inhibition of L.fermenti by (I) was recovered competitively and specifically by thiamine, and its inhibition index was 55,000. However, the inhibition of (I) for Kl.apiculata was not recovered by any vitamin. The acid-catalysed cyclization product of (I) ; phenyltriazinothiamine (2-phenyl-4-[(2-methyl-4-amino-5-pyrimidinyl)-methyl]-5-methyl-6-(2-hydroxyethyl)-2,5-dihydro-1,2,4-triazinium chloride HCl) (II) showed the same inhibition activity as (I). Reversible conversion was confirmed by means of either absorption spectra or titration curves between (I) and (II) by changing of pH in its aqueous solution. Growth inhibitory effect of (I) seemed to be due to (II) which was converted form of (I) in broth.

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A preliminary experiments were done for studying the effect of phytine on the metabolism of microorganisms. For the solubilization of Ca-phytate, polyoxyethylene cetylalcohol (BC-TX15) was found to be most suitable among five surface active agents, tested. BC-TX15 proved to have no inhibiting effects on the growth and acid production of Lactobacillus acidophilus, at the concentration of 0.01-0.1% in the medium.

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In the present paper, some additional data are presented which support the previously proposed formula (4-thiamine-SCu)・thiamine-SCuS-thiamine-2H_2O for a crystalline thiamine-copper complex. The proof for the thiol structure of the complex involves the negative thiochrome reaction for its ethylene glycol solution. Two components of the complex were confirmed by paper chromatography and fractionation by 95-98% ethanol. Bivalency of copper in the complex was ascertained by the elimination of copper with EDTA. The results of the stoichiometrical studies, including its convertion to thiamine, removal of copper with EDTA, and its dissolution with thiamine of thiol type, supported the above proposition.

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Hexa-, tetra- and mono-fatty acid esters of myoinositol were synthesized by various methods, e.g. by heating myoinositol or its 1,2-isopropiridene derivatives with acid anhydrides of various fatty acids, or by ester exchanging reaction with methyl esters of fatty acids under coexistence of sodium methoxide as catalyst. Properties of these fatty acid esters of myoinositol were described in respect to their nutritional and pharmaceutical usefulness.

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Of fatty acid esters of myoinositol examined, myoinositol-hexaacetate, -hexapropionate, and -hexabutyrate showed similar growth promoting effect as free myoinositol upon young rats, whereas -hexavalerate, -tetrabutyrate, -monooleate and -monolinoleate showed almost no growth effect and some of them showed rather inhibitory effect. Lipotropic effect of the fatty acid esters of myoinositol having growth promoting effect on young rats were then examined by Handler's procedure, and it was found that they all showed beneficial effect on the repression of fatty liver. The lipotropic action of myoinositol hexanicotinate was obscure.

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Thiamine and its mono-, di- and triphosphates were successfully separated on thin layer of Silica gel G, using pyridine・water・ammonia・methanol・glacial acetic acid (6 : 6 : 5 : 1 : 1) as developer. The Rf values of thiamine and its mono-, di- and triphosphates were found to be 0.92,0.50,0.17 and 0.08,respectively. The detection of spots was made by thiochrome fluolescence method. For this purpose the mixture of ethanol・10% NaOH・2.5%K-ferricyanide (2 : 1 : 0.05) was found to be most suitable.

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In contrast to the well-known strict stereo-specificity ascertained in the other vitamin B_<12> coenzyme-dependent reactions involving a hydrogen shift, such as the mutation of L-glutamate to L-threo-β-methylaspartate or of succinyl-CoA to L-methyl malonyl-CoA, comparison has not yet been made between the reactivities of D (-)-propanediol and of its L(+)-isomer. This paper showed that both the isomers could be converted to propionaldehyde, but the D-isomer was 1.5 to 2 times reactive than its L-isomer. An inhibtiion of the reactivity was observed if a high concentration of the L-form or the DL-form was used as a substrate. It appears interesting that the simultaneous addition of the L-form depressed the reactivity of the D-form. Presumptive mechanisms on the interaction between the stereoisomeric substrate and the enzyme are discussed.

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A green substance whose visible absorption spectrum was similar to that of vitamin B_<12s> was obtained by heating cyanocobalamin in 30% NaOH at 120℃ for 1 hour, and when oxidized by air it turned via brown to red and yielded 8-aminocobyrinic acid-c-lactam as a main product. The latter compound also turned green by the same alkali treatment. The green substance reacted with methyl iodide to give mainly Co-methyl-8-aminocobyrinic acid-c-lactam, which was identified by paper chromatography, paper electrophoresis, ultraviolet, visible and infrared absorption spectra. Thus, it was shown that the cobalt atom in a corrinoid compound was reduced to the same state as in vitamin B_<12s> by a vigorous alkali-treatment, and a reduction mechanism of cobalt atom by the action of hydroxyl ion was discussed.

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When cyanocobalamin was heated in 0.4% NaOH at 100℃ for 10 minutes in a nitrogen atmosphere, a yellow-brown substance was formed whose absorption spectrum was similar to that of vitamin B_<12r>. The product, a mixture of neutral and mono- to tri-basic acid components, was readily oxidized by air, and it was found to be reactive with alkyl halide. Neutral components of the reaction products of the yellow-brown substance with methyl iodide and n-butyl bromide were identified respectively with Co-methyl-and Co-n-butyl-derivatives of dehydrocobalamin, by their absorption spectra and by the properties and behaviors of their photolysis and cyanide treatment products in spectra, paper chromatography and in re-treatment with alkali. Therefore, the acidic components were considered to be respectively carboxylic acids derivatives of Co-methyl- and Co-n-butyl-dehydrocobalamin. While cyanocobalamin and aquo (or hydroxo) cobalamin turned yellow-brown rapidly by this alkali treatment, cyano-dehydrocobalamin and aquo (or hydroxo)-dehydrocobalamin changed very slowly. From these facts it is considered that the occurence of the yellow-brown color was due to the reduction of cobalt atom accompanied by the dehydrogenation on the ring B in the corrin nucleus.

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The author found an enzyme which produces riboflavin cyclic-2', 5'-mononucleotide from riboflavin in a salting out fraction by 70-80% saturation of ammonium sulfate of cell-free extract of Rhizopus oryzae. The enzyme requires guanosine-, inosine- or uridine-5'-triphosphate and some other unknown cofactors, while adenosine- or cytidine-5'-triphosphate is inactive.

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Investigation was made on the physical and chemical properties of O-acetoglycoloyl-S-furoylthiamine (AFT), C_<21>H_<24>N_4O_7S. The crystals are colorless, odorless and nonhygroscopic, having mp. 118℃. Ultraviolet absorption of its aqueous solution was examined at various pHs and it was found that the absorption maxima were shifted with change of pH, and isosbestic points were 238,270 and 294mμ. Dissociation constants obtained by the titration curve are Ka 2.24×10^<-6>. Solubilities in various solvents were measured. In aqueous solution AFT is slightly soluble at pH 5-7,but readily soluble at pH below 5. Rf value is 0.73,when a developing solvent consisted of n-butanol・acetic acid・water (4 : 1 : 5) is used. AFT was found to be most stable at pH 4 in the aqueous solution.

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Some biological properties of a new thiamine derivative, O-acetoglycoloyl-S-furoylthiamine (AFT) was investigated. In thiamine-requiring organisms, AFT exerted almost equal growth-promoting effects to that of thiamine hydrochloride. In thiamine deficient rat, longer duration of this effects were observed at higher dose of AFT. Purified thiaminases of bacilli could not decompose this compound. As compared with thiamine hydrochloride, AFT produced higher thiamine and cocarboxylase levels in blood by parenteral administrations. This high levels of thiamine and cocarboxylase were maintained for many hours.

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Among many derivatives of S-acylthiamines synthesized in a series of studies on thiamine, O-acetoglycoloyl-S-furoylthiamine (AFT) was found most remakable in biological properties. In present paper, dynamic pharmacological effects of AFT were studied. Results show that the effect of AFT is milder on acute toxicity of mice, systemic blood pressure and respiration of cats, isolated heasts of toads and excised intestine of guinea pigs, while it has a stronger vasodilating effect of coronary, renal and femoral arteries of dogs than that of thiamine hydrochloride.

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The distributions of O-acetoglycoloyl-S-furoylthiamine (AFT)-^<35>S and thiamine-^<35>S in mice have been studied autoradiographically at various times after an intravenous injection. The results of the autoradiographic distribution are shown in Fig.1-14. When AFT-^<35>S was administered, radioactivities in the heart muscle, skeletal muscles, blood and brain were observed to be higher than in the case of thiamine-^<35>S. In these organs, the ^<35>S of AFT-^<35>S penetrated at higher concentration and was remained for a longer time than the ^<35>S of thiamine-^<35>S.

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The authors have reported in the previous paper the autoradiographic distribution of O-acetoglycoloyl-S-furoylthiamine (AFT)-^<35>S and thiamine-^<35>S in whole mice. In the present study, the accumulations of ^<35>S in the organs, such as liver, kidney, brain, muscles (heart and masseter) stomach, glands (submaxillary and harderian) and blood, were investigated after an intravenous injection of AFT-^<35>S and thiamine-^<35>S in rats. In blood, muscles, stomach, and harderian gland, AFT-^<35>S has a superiority over thiamine-^<35>S on affinity to the organs and on maintenance of high ^<35>S valus of the organs.

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In the previous paper, O-acetoglycoloyl-S-furoylthiamine (AFT) was found to have predominant biological properties. In the present paper, the authors studied how AFT changes into what forms of thiamine in the tissues after administration. It was confirmed that almost all the AFT that was given subcutanously changed into phosphoric esters of thiamine in the tissues within an hour. Concentration of cocarboxylase formed from AFT was found to be higher than from thiamine hydrochloride in the various organs, especially in the heart.

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