Morisaki Masuo

Substrate specificity of adrenocortical cytochrome P-450scc—I. Effect of structural modification of cholesterol side-chain on pregnenolone production

Abstract Thirty four cholesterol analogues with modified side chain were chemically synthesized and incubated with a highly purified preparation of cytochrome P-450scc. It was shown that five to ten carbon sidechain are required for the cleavage reaction to occur and that structural modification in the side-chain especially around C-23 and C-25 positions either decreases or increases the yield of pregnenolone. The results suggest that the enzyme requires a relatively low, but not totally unlimited specificity for the side-chain structure of the substrate.

Nutritional effect of possible intermediates of phytosterol dealkylation in the silkworm, Bombyx Mori

Abstract Several possible substrates and intermediates of phytosterol dealkylation were tested for their ability to support growth and development in the silkworm, Bombyx mori . These compounds were classified into “effective” (fully substitutive for cholesterol), “partially effective” (partially supporting growth) and “ineffective” These results are discussed in relation to the mechanism of phytosterol dealkylation in insects.

Synthesis of 24,28-iminofucosterol and its inhibitory effects on growth and steroid metabolism in the silkworm, Bombyx mori

Abstract 24,28-Iminofucosterol (I) has been synthesized from fucosterol acetate via addition of iodine isocyanate. The steroidal aziridine (I) disrupted normal growth and development of larvae of the silkworm, Bombyx mori and was found to be a potent inhibitor of dealkylation of β-sitosterol.

Substrate specificity of adrenocortical cytochrome P-450scc—II. Effect of structural modification of cholesterol A/B ring on their side chain cleavage reaction

Abstract Eight cholesterol analogs with modified A/B ring were incubated with a highly purified preparation of cytochrome P-450 scc . It was shown that only the side chain of 3-epicholesterol and cholestenone were cleaved, whereas none of cholesterol esters were the substrate for P-450 scc .

Synthesis and biological activity of 25,26,27-trisnor-vitamin D3 24-oic acid and its 1α-hydroxyl analog

Abstract Because 1,25-dihydroxy vitamin D undergoes side-chain cleavage and oxidation in vivo , an anticipated metabolite is 1α-hydroxy-trisnor-vitamin D 3 24-oic acid. A synthesis for this metabolite and trisnor-vitamin D 3 24-oic acid has been devised. Baeyer-Villiger rearrangement of 5,6-dibromo-24-oxo-cholesteryl acetate and its 1α-acetoxyl analog gave the corresponding cholenoate derivatives, and those were converted to trisnor-vitamin D 3 24-oic acid and its 1α-hydroxyl analog, respectively. The 1α-hydroxy-25,26,27-trisnor-vitamin D 3 24-oic acid (1α-OH-24-COOH trisnor-vitamin D 3 ) was tested for biological activity using rats fed a low calcium, vitamin D-deficient diet. It stimulated intestinal calcium transport 6 h after intravenous administration although the response is significantly less than that to an identical base of 1,25-dihydroxy vitamin D 3 (1,25-(OH) 2 D 3 ). This compound given at 125 ng per rat did not stimulate bone calcium mobilization.