The effect of vitamin B12(B12)-deficiency on the activities of hepatic methionine synthase, homocysteine methyltransferase, and cystathionine β-synthase was investigated in rats. The rats bred from B12-deficient dams were fed the B12-deficient diets for 150 days after weaning. Growth retardation of the B12-deficient rats was already observed on day 30 and continued through 150 days. But dietary supplementation of 0.5% DL-methionine slightly improved the growth retardation. Urinary excretion of methylmalonic acid increased to about 15 mg/mg creatinine and hepatic B12 concentration declined to about 2 ng/g liver after a 150-day feeding of the B12-deficient diets. Hepatic methionine synthase activity in rats fed the B12-deficient diets supplemented with or without methionine decreased to about 5% of B12-supplemented controls. Hepatic betaine-homocysteine methyltransferase activity showed no significant change caused by B12-deficiency. Hepatic cystathionine β-synthase activity in rats fed the B12-deficient diets supplemented with or without methionine decreased to about 61% and 27% of their B12-supplemented controls, respectively, but the decrease was partially improved by methionine supplementation. In conclusion, the rats bred from B12-deficient dams showed a severe B12-deficiency after a 150-day feeding of the B12-deficient diets. The decrease of hepatic cystathionine β-synthase activity was supposed to be due to the adaptation by the defect of methionine resynthesis.
Normal and vitamin B6-deficient rats received an intraperi-toneal injection of 30mg/100g of body wt, and the contents of metabolites in kidney or plasma and the related enzyme activities in kidney were determined. The contents of kynurenine and 3-hydroxykynurenine in B6-deficient rat plasma and kidney were much higher than those in normal rat. The changes of those contents in plasma were parallel to those in kidney, but not in liver. The contents of kynurenic acid and xanthurenic acid in B6-deficient liver, plasma, and kidney were also much higher than those in normal rats. However, the changes of those contents in plasma were parallel to those in liver, but not in kidney. Xanthurenic acid and kynurenic acid accumulated to a much greater extent in kidney than in plasma and liver. Kidney kynureninase activity was very low, but kynurenine aminotransferase activities were very high. These observations indicated that the production of xanthurenic acid after tryptophan injection was favorable in B6-deficient kidney with respect to enzyme activities and substrate concentrations, and suggested that kidney took up kynurenine or 3-hydroxykynurenine from blood and after conversion of them it excreted xanthurenic or kynurenic acid into urine.
The effect of erythorbic acid (ErA) administration on activities of liver aniline hydroxylase, liver acid phosphatase, and serum alkaline phosphatase, and the content of liver cytochrome P-450 was studied to determine whether or not ErA would affect the availability of ascorbic acid (AsA) in normal and AsA-deficient guinea pigs. In experi-ment I, changes of the enzyme activities and liver cytochrome P-450 content in the guinea pigs administered AsA and/or ErA and sacrificed on days 4, 10, 16, and 30 were examined. Moreover, in experiment II, after 16 days of depletion of AsA, the guinea pigs were administered AsA and/or ErA. These animals were sacrificed on days 0, 4, and 20 of the repletion period, after which the activities of drug metabolic enzyme and phos-phatases and content of cytochrome P-450 during recovery were observed. The enzyme activities and cytochrome P-450 content of AsA-supplemented guinea pigs were similar to those of ErA-supplemented animals and also similar to those of both AsA and ErA-supplemented guinea pigs throughout the experimental period. During the repletion of the AsA-depleted guinea pigs, there were no significant differences in these enzyme activities and cytochrome P-450 content among the animals administered AsA and/or ErA. These results suggested that ErA adminis-tration may not affect the AsA availability in the guinea pigs.
A study was conducted to investigate the effects of a megadosage of free RRR-alpha-tocopherol in healthy college student volunteers. Of 19 volunteers, 14 were given daily doses of 600 mg (900IU) of RRR-alpha-tocopherol for 12 weeks, and the remaining 5 were given identical placebo capsules. The investigation was performed by the singleblind method. Alpha-tocopherol levels were measured in plasma, red blood cells '(RBCs), platelets, leucocytes (WBCs), and buccal mucosal cells. Alpha-tocopherol in plasma, RBCs, and WBCs rose, reached a maximum level 4 weeks after commencement of administration, and then remained at a plateau, while platelet and buccal cell levels reached a maximum level after 12 weeks of administration. The maximum levels in all the subjects were 2.5 to 3 times the baseline values. During the study, there were no changes in laboratory values for thyroid, liver, or kidney functions, and coagulation activity (including the vitamin K-dependent Hepaplastin test and PIVKA-II) or immunoglobulin levels. Healthy status continued without any abnormal symptoms, and without any subjective complaints on the questionnaire. In the control group also, no changes occurred during the investigation. Gamma-tocopherol changes were measured in plasma and RBCs. As plasma and RBC tocopherol levels rose after administration, the isomer levels were suppressed in both plasma and RBCs.
Irradiation of organic sulfinates such as hypotaurine and cysteine sulfinic acid in the presence of catalytic amounts of flavins led to the oxidation of its sulfinic groups (-SO2H) to the corresponding sulfonates. The process of hypotaurine oxidation in the presence of riboflavin, followed by absorbance decrease at 220 nm and by ion-exchange chromatography, showed a pseudo-first-order kinetics at pH 6.0. The k value depended linearly on flavin concentrations. The reaction rate was higher at acidic pH. Although the reaction rate was not affected by the addition of superoxide dismutase or catalase, superoxide ions were supposed to be by-products of the reaction. The effectiveness of allyl alcohol as a scavenger pointed to a free-radical mechanism of the reaction. We propose a new reaction mechanism involving sulfinic radicals on this photochemical reaction.
The effect of oral ingestion of different fractions of onion (Allium cepa)-extract, residue, and whole-at a dose level equivalent to intake of 50g of onion per day for a 70-kg man, for 30 days, to male adult, normal, albino rats was studied on blood and erythrocyte membrane lipids and certain membrane-bound enzymes. Onion extract and residue showed hypercholesterolemic effect, while whole onion showed hypocholesterolemic effect in blood. In erythrocyte membranes, all the fractions had hypocholesterolemic and hypolipidemic effect, which was accompanied by changes in the erythrocyte membrane enzymes studied, i.e., alkaline and acid phosphatase, 5'-nucleotidase, total and Mg2+ ATPase. The above study indicated that it is safer to take whole onion rather than onion residue or extract, because whole onion could lower the blood cholesterol level even in normal condition and has a less pronounced effect on the micro-evironment of the cells.