TY - JOUR
T1 - Binding and hydroxylation of sulfoconjugated steroids in adrenal cortex mitochondria
AU - Montelius, J.
AU - Gustafsson, J. Å
AU - Ingelman-Sundberg, M.
AU - Rydström, J.
N1 - Funding Information:
This work was supported by grants from the Swedish Natural Science Research Council (K2162-024), the Swedish Cancer Society (75 : 124 and 102-13’7-lOXA), and the Swedish Medical Research Council (03X-2819).
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1977/9/28
Y1 - 1977/9/28
N2 - 1. 1. Binding and hydroxylation of deoxycorticosterone 21-sulfate, testosterone 17-sulfate, cholesterol 3-sulfate and the corresponding free steroids by the hydroxylase systems in adrenal cortex mitochondria was studied. Deoxycorticosterone 21-sulfate binds to cytochrome P-450 and gives rise to a type I difference spectrum with a peak at 388 nm and a trough at 422 nm similar to that produced by deoxycorticosterone. The maximal extents of absorption change are similar for the free and the sulfoconjugated steroid. However, the concentration required for half-maximal binding to cytochrome P-450 is about two orders of magnitude lower for the free steroid as compared to the sulfoconjugated steroid. Similar results were obtained with testosterone and testosterone 17-sulfate. 2. 2. The absorption changes produced by deoxycorticosterone and testosterone are not additive indicating that these steroids bind to the same species of cytochrome P-450. With either of these steroids addition of the corresponding sulfoconjugated steroid does not result in further absorption change suggesting that free and sulfoconjugated steroid bind to the same species of cytochrome P-450. Likewise, it appears that the same species of cytochrome P-450 binds both cholesterol and cholesterol 3-sulfate. 3. 3. With malate as reducing agent deoxycorticosterone 21-sulfate is hydroxylated by adrenal cortex mitochondria to corticosterone 21-sulfate at a rate of about 0.075 nmol/min per mg protein i.e. about 7% of the rate of hydroxylation of the free steroid. Neither testosterone 17-sulfate nor testosterone is hydroxylated at any appreciable rate. It is concluded that in intact adrenal cortex mitochondria sulfoconjugated steroids may be metabolized by the normal pathways for the free steroids but at reduced rates.
AB - 1. 1. Binding and hydroxylation of deoxycorticosterone 21-sulfate, testosterone 17-sulfate, cholesterol 3-sulfate and the corresponding free steroids by the hydroxylase systems in adrenal cortex mitochondria was studied. Deoxycorticosterone 21-sulfate binds to cytochrome P-450 and gives rise to a type I difference spectrum with a peak at 388 nm and a trough at 422 nm similar to that produced by deoxycorticosterone. The maximal extents of absorption change are similar for the free and the sulfoconjugated steroid. However, the concentration required for half-maximal binding to cytochrome P-450 is about two orders of magnitude lower for the free steroid as compared to the sulfoconjugated steroid. Similar results were obtained with testosterone and testosterone 17-sulfate. 2. 2. The absorption changes produced by deoxycorticosterone and testosterone are not additive indicating that these steroids bind to the same species of cytochrome P-450. With either of these steroids addition of the corresponding sulfoconjugated steroid does not result in further absorption change suggesting that free and sulfoconjugated steroid bind to the same species of cytochrome P-450. Likewise, it appears that the same species of cytochrome P-450 binds both cholesterol and cholesterol 3-sulfate. 3. 3. With malate as reducing agent deoxycorticosterone 21-sulfate is hydroxylated by adrenal cortex mitochondria to corticosterone 21-sulfate at a rate of about 0.075 nmol/min per mg protein i.e. about 7% of the rate of hydroxylation of the free steroid. Neither testosterone 17-sulfate nor testosterone is hydroxylated at any appreciable rate. It is concluded that in intact adrenal cortex mitochondria sulfoconjugated steroids may be metabolized by the normal pathways for the free steroids but at reduced rates.
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U2 - 10.1016/0005-2760(77)90208-9
DO - 10.1016/0005-2760(77)90208-9
M3 - Article
C2 - 901802
AN - SCOPUS:0017665989
SN - 0005-2760
VL - 488
SP - 502
EP - 511
JO - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
JF - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
IS - 3
ER -