The metabolism of 1α-OH-D_3 was studied in rat perfused liver with [2-^3H]-1α-OH-D_3. [2-^3H]-1α-OH-D_3 was converted very rapidly to a more polar metabolite, which was identified as 1α,25-(OH)_2-D_3 by co-chromatography with synthetic 1α,25-(OH)_2-D_3 as well as by gas chromatograph-mass spectrometry. The 25-hydroxylation of 1α-OH-D_3 is not under metabolic control unlike the 25-hydroxylation of D_3. There are two modes of 25-hydroxylation of D_3 in the liver, which seem to be closely related to the mechanism of control of 25-0H-D_3 production by the liver. A laboratory model of renal osteodystrophy was developed in rats by a single injection of glycopeptide isolated from renal cortical tissues of rats according to the method used by Shibata et al., to induce glomerulonephritis. We found that this renal damage led to severe secondary hyperparathyroidism and osteodystrophic changes, such as osteitis fibrosa associated with osteomalacia. In the model the escape of significant amounts of 25-0H-D_3 into the urine was much severe than that of 1α-OH-D_3. The comparative effectiveness of D_3 and its derivatives in curing hyperparathyroidism and osteodystrophic bone lesions was examined in this model of renal osteodystrophy. 1α-OH-D_3 was the most potent one in curing osteodystrophic bone changes, followed by 1α,25-(OH)_2-D_3, 25-0H-D_3 and D_3 in this order. The same dose level of 1α-OH-D_3 was more effective than 1α,25-(OH)_2-D_3 in enhancing plasma 1α,25-(OH)_2-D_3 levels. Thus, the potency of 1α-OH-D_3 appeared to be most stronger than that of 1α,25-(OH)_2-D_3. These results suggest that 1α-OH-D_3 is a good drug of choice in the treatment of renal osteodystrophy.

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(1) A thiamin kinase defective mutant of Escherichia coli W (70-23-102) accumulated free thiamin in the presence of glucose. The overshoot phenomenon of thiamin was not observed. This mutant cell accumulated nearly the same amount of thiamin diphosphate as the kinase positive cell, while the maximum accumulation of free thiamin was ca. 1/4. (2) Characteristics of uptake reaction were featured by those values like K_m of 0.8 nM, optimum pH of 6.8, optimum temperature of 45℃, and V_<in> of 31 nmol/g/min. (3) Thiamin-exit reaction of this mutant showed nearly complete NaN_3-inhibition, dependency on cellular thiamin (FIG. 8), optimum pH of 8.0, optimum temperature of 34℃, and V_<out> of 14 nmol/g/min.

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