Versatile steroid molecules at the end of the aldosterone pathway.
18-hydroxycorticosterone converts spontaneously and reversibly to a variety of less polar forms and derivatives, some of which are precursors to aldosterone. In particular, 21-hydroxy-11 beta, 18-oxido-4-pregnene-3,20-dione (18-DAL) is hydroxylated to aldosterone with high yields in the presence of malate and NADP+, at pH 4.8. 18-DAL also behaves as a metabolic intermediate between 18-OH-B and aldosterone according to time-course and trapping experiments. Consequently, the final steps of the aldosterone pathway at pH 4.8 could be identified as 18-OH-B, 18-DAL and aldosterone, in this sequence. The submitochondrial distribution of aldosterone biosynthesis is compatible with this postulate. The work also shows that some forms of 18-OH-B are promoters of hydrogen transport in renal tubuli and that this regulation may be independent of sodium reabsorption. These results suggest a regulatory model, new in steroid biology, according to which steroid molecules bearing an oxidized angular C18-methyl may undergo structural changes between precursor ("P") and hormonal ("H") forms in response to homeostatic requirements.
Lantos
C P
CP
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Damasco
M C
MC
Aragonés
A
A
Ceballos
N R
NR
Burton
G
G
Cozza
E N
EN
D015069:18-Hydroxycorticosterone / Q000378:metabolism; D000136:Acid-Base Equilibrium; D000302:Adrenal Cortex / Q000502:physiology; D000450:Aldosterone / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D011498:Protein Precursors / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*
D011498:Protein Precursors; D013256:Steroids; C020274:18-deoxyaldosterone; D000450:Aldosterone; D015069:18-Hydroxycorticosterone