It has been concluded in the previous discussion on modified thiamine compounds ^<7>)that any modification of the thiamine molecule will cause loss of activity, unless the modified compounds can be reverted to thiamine in vivo. The similar conclusion will be applied to any modification of vitamins ; their vitamin activity can be expected only when the modified derivatives will be easily converted to the original vitamins in animal or human metabolism. Successful design of new vitamin derivatives as drugs will be differentiated into two directions : 1) More stabilized and easily absorbable modification of vitamins as effective vitamin preparations, 2) more specific and non-revertible modification of vitamins as antivitamins or permanently altered compounds as pharmacological agents. It is necessary to evaluate modified compounds of vitamins from the standpoints of rational development and application of drugs. Misbranded use of modified thiamine compounds such as "acrtive vitamin B_1 preparations" or exaggerated effectiveness should be strictly controlled thru rational evaluation of each modified compound.

View full abstract

As a fundamental study for the application of 5'-D-riboflavin-α-D-glucopyranoside (B_2-5'-α-gl) as food additive, both the influence of light on B_2-5'-α-gl and its degree of bitter taste were examined. B_2-5'-α-gl dissolved in buffer solution of pH 3,6 and 8 was found always to be more stable for light than riboflavin and flavin mononucleotide. It was pointed out from organoleptic examination that a bitter taste of riboflavin was fairly stronger than that of B_2-5'-α-gl.

View full abstract

In order to clarify a metabolic role of pantothenic acid (PaA) derivatives accumulated in rat liver, in the experiments with ^<14>C-pantothenic acid, incorporation of the isotope into the derivatives was determined. The PaA derivatives were extracted from the liver of PaA-deficient rat after administration of ^<14>C-PaA for eight days, then applied on DEAE-cellulose column chromatography. Three radiocative fractions, peak A, B and C were obtained and also detected by microbiological assay with L. arabinosus. It was found that peak A was identified with paA, peak B with 4'-phosphopantetheine and peak C with CoA, respectively, by means of paper chromatography. The ratio of radioactivity per pantothenic acid of the three compounds were 2 : 1 : 1. In the additional labelling experiment, however, the specific radioactivity of peak B (4'-phosphopantetheine) was 2.5 times as much as that of peak C (CoA). This suggests that 4'-phosphopantetheine existed in rat liver acts as a precursor of CoA biosynthesis, but not a decomposition product of CoA.

View full abstract

The activity of α-keto acid dehydrogenases ; pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase in liver mitochondria of thiamine-deficient, normal and thiamine-loading rats was estimated by the spectrophotometric method using ferricyanide as electron acceptor. The activity of α-keto acid dehydrogenases decreased significantly in thiamine-deficient rats, but by the addition of thiamine diphosphate in vitro, the activity was fairly elevated though not complete. Single intraperitoneal injection of thiamine (2mg) to deficient rats restored rapidly the activity to the extent of the normal rats. No change of the α-keto acid dehydrogenases'activity was observed in rats 4 hours after single intraperitoneal injection of thiamine (4mg). These suggest that there has been no effect of α-keto acid dehydrogenase activity with a large dose administration of thiamine. However, in the rats administered daily thiamine (2mg) for 8 days, pyruvate dehydrogenase activity showed a tendency of increase by addition of thiamine diphosphate, in vitro.

View full abstract

The stability of the methyl group attached to cobalt atom of methylcobalamin (CH_3-B_<12>), and hence the structural integrity of CH_3-B_<12> were studied in rats using ^<14>CH_3-B_<12> and CH_3-^<57>Co-B_<12> in vitro as well as in vivo. CH_3-B_<12> was relatively stable in the intestinal canal, and the radioactivity in the mucosa was mostly CH_3-B_<12> in the absorptive phase. When incubated with whole blood, the methyl group was not detached. Following parenteral injection of ^<14>CH_3-B_<12>, part of it was excreted in urine unchanged, and practically no release of methyl group was noted during filtration through the kidney. During incubation with liver homogenate, certain portion of the CH_3-B_<12> lost the methyl group but the reaction did not proceed beyond it. These data indicate that a good portion of oral CH_3-B_<12> is absorbed as such, and the compound is relatively stable in tissues, losing the methyl group gradually.

View full abstract

In the present investigation, the influences of age and vitamin E on the fatty acid composition of red blood cell membrane were studied in rats and the following results were obtained : In the vitamin e deficient rat, the decrease of palmitic acid and the increase of polyunsaturated long chain fatty acid (carbon number>20) on the fatty acid pattern were observed. This phenomenon resembles closely an alteration in aging. In order to separate the blood into fresh and aged cells and to investigate the effect of vitamin E on these different aged cells, the centrifugal fractionation method was applied upon the bloods obtained from individual animals. The decrease of palmitic acid and the increase of polyunsaturated long chain fatty acids were observed in aged cells obtained from vitamin E deficient young animals (6 months), but not in them from vitamin E sufficient young animals. This age-dependent change on fatty acid pattern was more intensified in old animals (24 months) regardless of vitamin E. It was observed that vitamin E deficiency accelerated the age-dependent changes on fatty acid pattern of the red blood cell membrane. However, it was suggested that the changes might be brought not only by vitamin E and the other nutrients but also by the essential biological regulation.

View full abstract