Effects of L-ascorbate 2-sulfate (AAS) on fatty liver and hyperlipidemia induced by various treatments were studied in rats and guinea pigs. L-Ascorbic acid (AA) (50 or 175mg/kg), a reference compound, lowered the lipid levels in the serum and/or liver in guinea pigs, while AA had little effect in rats. On the other hand, AAS (300mg/kg) was effective in both animals. In rats, AAS lowered cholesterol and triglycerides in the serum from ethionine-treated animals and in the liver from orotic acid-supplemented animals. In guinea pigs, this compound lowered cholesterol and triglycerides in the serum from ethionine-treated animals, lipids in the liver from cholesterolsupplemented animals, and lipids in the serum and liver from scorbutic animals. AA markedly increased the content of AA in the organs in all experiments, while AAS had a slight effect. Thus, it is suggested that AAS exerts its hypolipidemic and lipotropic effects by the specific actions of AAS.

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4'-Substituted pyridoxine analogues (4'-PN analogues), which were potent antagonists of vitamin B6, induced severe convulsions in mouse which could be prevented by vitamin B₆. To elucidate the mechanism of the convulsive action, the effect of 4'-PN analogues on partially purified pyridoxal kinase (PL-kinase) from mouse brain was studied. 4'-Methoxypyridoxine (4'-MPN), 4'-ethoxypyridoxine (4'-EPN), 4'-propoxypyridoxine (4'-PPN) and 4'-isopropoxypyridoxine (4'-iso PPN) were found to be powerful inhibitors of PL-kinase and competed with pyridoxal (PL). There was a good relationship between mouse convulsions and inhibitory activities of PL-kinase. We also studied whether 4'-MPN, 4'-EPN, 4'-PPN and 4'-isoPPN were used as substrates of PL-kinase. High-performance liquid chromatography was used to separate 4'-PN 5'-phosphate analogues and ADP which were formed in the enzyme reaction, and to measure them quantitatively. The results showed that 4'-MPN, 4'-EPN, 4'-PPN and 4'-isoPPN were also phosphorylated by PL-kinase like 4'-deoxypyridoxine.

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In the photochemical conversion of cholesta-5, 7-diene 1α, 3 β-diol (1α-OH-7-DHC) to 1α-hydroxyvitamin D₃ (1α-OH-D₃) via 1α-hydroxyprevitamin D₃, the effect of irradiated wavelength was in vestigated by using monochromatic ultraviolet (UV) rays obtained from a spectroirradiator. The yield of 1α-OH-D₃ and the remaining rates of 1α-OH-7-DHC in the irradiated solutions were determined by a method using high-performance liquid chromatography (HPLC). When a 1α-OH-7DHC solution in ethanol (1.0mg/ml) was irradiated with monochromatic UV light in the range of 253-332 nm with the quantum of either 4.275×108 or 8.55×10⁸ erg/cm², a mountain shape with a maximum at 295 nm was observed on the relationship between yield of 1α-OH-D₃ and irradiated wavelengths. The phenomenon was similar to those observed on the formation of vitamin D₂ or D₃ by irradiating ergosterol or 7dehydrocholesterol (5, 6). However, the former's yield (2.3%) obtained by irradiation with light of 321 nm was far lower than the latter's respective data (ca. 13%), while the former's remaining rate of 1α-OH-7-DHC was also lower than the latter's. The results suggested that comparatively large amounts of byproducts might be formed in the former's case. The phenomenon agreed with the observations mentioned by Barton et al. (2, 3) that the irradiation of 1 α-OH-7-DHC with light in the range of 310-330 nm gave some undesirable byproducts. Therefore, we found a new filter solution capable of effectively removing the UV light in the undesirable range and the irradiation experiment using the newly found filter solution was performed. The results showed that the use of the filter solution gave higher yield of 1α-OH-D3 and a higher remaining rate of unreacted 1α-OH-7-DHC than the respective data obtained from irradiation by using other filter solutions incapable of removing the undesirable UV light. The newly found filter solution was stable to UV irradiation. From these results and observations, we concluded that the filter solution was very useful for the photochemical reaction of 1α-OH-7DHC to 1α-OH-D₃.

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Protaminobacter ruber was cultured in a medium containing [⁵⁷Co]cyanocobalamin with a “two-step cultivation method” and the forms of vitamin B₁₂ compounds in the cells were examined. Methyl cobalamin was detected in the early phases of growth and reached a maximum of about 40% of ail cobalamins extracted from the cells. In the stationary phase of growth, almost all cobalamins consisted of ade nosylcobalamin. Recultivation of the cells of the stationary phase in a fresh medium resulted in the conversion of adenosylcobalamin into methylcobalamin. Interconversion of methylcobalamin and adenosyl cobalamin was presumed from these facts.
The formation of adenosylcobalamin from methylcobalamin was de monstrated with a cell-free extract system from P. ruber. The rate of conversion of methylcobalamin into adenosylcobalamin was highest among several cobalamin analogs tested. Propylation of 5-methyltetrahydrofolate: homocysteine methyltransferase with 1-iodopropane did not affect this conversion reaction, which was probably catalyzed by methyltransferase and adenosyltransferase.

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The effect on the tryptophan-NAD pathway of feeding rats on a diet containing an amino acid mixture simulating rice protein plus the limiting amino acids, 0.4% of lysine ⋅ HCl, 0.2% of threonine, 0.100 of valine, 0.2% of isoleucine, 0.100 of methionine and 0.100 of histidine ⋅ HCl (basal diet + amino acids), was investigated using male weanling rats of the Sprague Dawley strain, and compared with the reference (basal diet), which did not contain the supplement of the limiting amino acids. These two diets were niacin-free. The weight gain in the “basal diet+amino acids” group was higher than that in the “basal diet” group in the early stage and the food intakes of rats in both groups were almost the same. Consequently, tryptophan intake per g rat body weight in the former group was lower than that in the latter group. Nevertheless, free tryptophan, total niacin and NAD content per g of liver and kidney of both groups were almost the same and remained constant during this experimental period. This was attributed mainly to the fact that tryptophan oxygenase [EC 1. 13. 11. 11] and quinolinate phosphoribosyl transferase [EC 2. 4. 2. 19] activities of organs in the “basal diet+amino acids” group were higher, and urinary excretion of tryptophan and its metabolites in the group was smaller than that in the “basal diet” group in the early stage. In the middle stage, tryptophan intake per g of rat body weight in both groups fell to half the level of the early stage. Nevertheless, NAD content was maintained at a constant level, urinary excretion of tryptophan and its metabolites was decreased, and picolinate carboxylase [EC 4. 1. 1. 45] activity of liver dropped. These results indicate that a strict regulation mechanism must exist for maintenance of NAD content of liver and kidney of rat for at least the 54-day feeding of these incomplete diets.

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The sites of stimulation of dietary sucrose-mediated changes in jejunal sucrase activity was investigated in rats refed on 5 g of a high sucrose diet following a 2-day fast. Actinomycin D was injected into rats 7.5 hr prior to, just before or 15 hr after the beginning of refeeding. Regardless of actinomycin D injection and respective periods, jejunal sucrase specific activity (sucrase activity per mg of mucosa protein) of rats 24 hr after the beginning of refeeding was significantly increased, but the significant increase in the segmental sucrase activity, sucrase activity per 15 cm segment, was remarkably inhibited by actinomycin D injection 7.5 hr prior to and just before refeeding. There was no difference in time-course changes in the sucrase specific activity after the beginning of refeeding between rats receiving actinomycin D injection 7.5 hr prior to refeeding and treated with saline injection in the same period. However, the significant rise of the segmental sucrase activity between 15 and 24 hr after the beginning of refeeding was remarkably inhibited by the actinomycin D injection. Hydroxyurea (a karyorrhexis agent) injection just before the beginning of refeeding affected neither the increase in jejunal sucrase specific activity nor that in the segmental sucrase activity, but the hydroxyurea injection 3 hr prior to refeeding caused a significant reduction of increases in the sucrase specific activity and the segmental sucrase activity. The significant increase in segmental sucrase activity 24 hr after the beginning of refeeding was not affected by a massive addition of surface-active agents into the refed diet and drinking water during the initial period of refeeding. These experimental results lent strong support to the idea that the stimulation of the response of jejunal sucrase activity to dietary sucrose in rats was produced in the crypt cell during the initial period of refeeding.

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The effect of food restriction on the intestinal weight and membrane digestive enzyme activities was observed in rats with diabetes induced by streptozotocin. The specific activities of disaccharidases of food non-restricted diabetic rats were not changed, but total activities were significantly increased due to the increase of intestinal mucosal weight. Restriction of food intake did not increase intestinal mucosal weight, but significantly increased the specific and total activities of disaccharidases in parallel with the increase of sucrase-isomaltase content.
On the other hand, experimental diabetes did not influence the activity of alkaline phosphatase and leucine aminopeptidase except for specific and total activities of alkaline phosphatase in food non-restricted rats.

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The hormonal regulation of α-amino β-carboxymuconate-ε-semialdehyde decarboxylase (picolinic carboxylase) was studied to clarify the change of tryptophan-niacin metabolism in the different physiological states. Hypophysectomized rats were administered with predonine hemisuccinate and various kinds of pituitary hormones for 2 or 4 days every 12 hr. The activity of their liver picolinic carboxylase was then assayed. The injection of predonine alone elevated the enzyme activity in hypophysectomized rats. On the other hand, rat or bovine pituitary extract was found to suppress such enzyme induction when it was administered prior to predonine injection. The enzyme-suppressing activity of the pituitary extract was lost by heat treatment or addition of proteolytic enzyme such as trypsin and chymotrypsin. These results indicate that the effective substances in the extract may be polypeptides. By gel filtration of bovine pituitary extract, two effective fractions were obtained, which were able to suppress the predonine-dependent induction of liver picolinic carboxylase. The molecular weights of these substances were estimated to be about 23, 000 and 2, 000-4, 000, respectively. Both of these effective substances were shown to be localized in the anterior lobe of hypophysis. In the many kinds of pituitary hormones tested, bovine somatotropin and mammalian prolactin were found to be effective in suppressing the predonine-dependent induction of liver picolinic carbo xylase in hypophysectomized rats.
To obtain some information on the mechanism by which liver picolinic carboxylase activity is elevated in diabetic rats, bovine somatotropin or rat pituitary extract was administered to diabetic rats for 4 or 7 days every 12 hr. This hormone treatment was not observed to depress the enzyme activity in the diabetic rats. These results are considred to suggest that changes in pituitary hormone are not responsible for the elevation of the enzyme activity in the diabetic rat.

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The regulation of tryptophan-niacin metabolism by pi tuitary and adrenocortical hormones was investigated. Hypophysectomized rats fed on a niacin-free purified diet were injected with bovine somatotropin, predonine acetate or both. The urinary excretion of N-methylnicotinamide (MNA) and N-methyl-2-pyridone-5 carboxamide (2-Py) after oral administration of tryptophan was then compared before and after the hormone treatment. The amount of urinary MNA was found to be increased after the injection of somatotropin, but decreased after the predonine injection. On the other hand, no change in urinary MNA was observed in the rats administered with both hormones. The amount of 2-Py appeared to be reduced by the predonine treatment, but was not affected by somatotropin injection. The activity of liver α-amino-β-carboxymuconate-c-semialdehyde decarbo xylase (picolinic carboxylase) was shown to be directly proportional to the ratio (oral tryptophan)/(urinary MNA). Moreover, the enzyme activity appeared to be inversely proportional to the concentration of niacin in liver. In addition, the amount of urinary MNA was suggested to be affected by the change of body weight gain.
The administration of both pituitary hormone and insulin failed to normalize the reduced urinary MNA excretion in diabetic rats, suggesting that any change in pituitary hormone was not responsible for the abnormal tryptophan-niacin metabolism in diabetes.

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