Stereochemistry of 1,2-hydrogen loss during aromatization in the brain.
The stereochemistry of hydrogen loss from C-1 and C-2 during aromatization in rat brain was studied using androstenedione containing a known distribution of isotopic label. Comparison of the tritium content of the estrone obtained from the aromatization of androstenedione labeled predominantly in the 1 alpha,2 alpha positions with that in estrone obtained from a parallel incubation using substrate with label in the 1 beta,2 beta orientation gave an estrone alpha/beta ratio of 3.6. This ratio compares with a calculated value of 4.3 for an aromatization mechanism involving loss of the 1 beta,2 beta-hydrogens. The distortion from the predicted value is due to the loss of tritium from the alpha-substrate which is unrelated to aromatization. The ratio determined experimentally is compatible with 2 beta-tritium loss since random or alpha-elimination from C-2 would yield alpha/beta ratios of 2.2 and 1.3 respectively. In an analogous manner the stereochemistry of tritium loss at C-1 was determined using [1 alpha-3H] and [1 beta-3H]androstenedione. The alpha/beta ratio of the isolated estrone was 3.6 which is in good agreement with the calculated value of 3.3 for 1 beta-tritium elimination. Our results therefore show that estrogen formation in the brain occurs with the same stereospecificity of hydrogen loss at C-1 and C-2 as in placental microsomes.
D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites; D001921:Brain / Q000201:enzymology*; D004970:Estrone / Q000096:biosynthesis / Q000302:isolation & purification; D006801:Humans; D006859:Hydrogen / Q000302:isolation & purification*; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology*; D051381:Rats; D013237:Stereoisomerism; D013379:Substrate Specificity
D004970:Estrone; D000735:Androstenedione; D006859:Hydrogen; D010088:Oxidoreductases; D001141:Aromatase