Mineralocorticoid hormones are responsible for controlling the
reabsorption of inorganic ions (Na+, Cl- and HCO3-) by the kidney.
Aldosterone, the main C21 mineralocorticoid, is primarily synthesized in
the cortex of the adrenal gland. Like all steroid hormones,
mineralocorticoids are derived from cholesterol; their biosynthesis is
tightly regulated by the hypothalamus-pituitary-gonadal axis. The
chronic steroidogenic response involves the
change in the expression of
steroidogenic genes while the acute response involves the quick delivery
of cholesterol to the site of the first enzymatic reaction. The rapid
flux of cholesterol from the outer to the inner mitochondrial membrane
(IMM) is mediated by the StAR protein. The IMM is the site where
Cyp11a1, the enzyme catalyzing the first and rate-limiting step in the
steroid biosynthetic pathway, is located. Overall there are two major
classes of enzymes: the heme-containing cytochrome P450 and the
hydroxysteroid dehydrogenase enzymes. The members of P450 superfamily
that participate in the pathway are membrane-bound mitochondrial or
endoplasmic reticulum (microsome) enzymes that utilize NADPH as an
electron donor. Two proteins mediate the mitochondrial electron transfer
- the flavin containing Fdxr and the iron-sulfur Fdx1; only one protein
mediates the microsomal electron transfer - the P450 (cytochrome)
oxidoreductase Por with two flavin cofactors. Dehydrogenases are
membrane-bound mitochondrial or microsomal enzymes that utilize NAD or
NADPH depending on whether the reaction is oxidation or reduction. The
27-carbon cholesterol is converted to the C21 pregnenolone in a series
of three chemical reactions that together constitute the step catalyzed
by Cyp11a1. Isoforms Hsd3b1 and Hsd3b2 can catalyze the conversion of
pregnenolone to progesterone. Desoxycorticosterone
(11-deoxycorticosterone) is generated from progesterone by Cyp21a1. Two
additional P450 enzymes, Cyp11b1 and Cyp11b2, are needed to generate
corticosterone, and subsequently aldosterone, respectively, in the zona
glomerulosa, or outer zone of the adrenal gland cortex. To see the ontology report for annotations, GViewer and download, click here. [click to see the ontology report for related GO term - GO:0032342, associated KEGG map - map00140 and related entry at Reactome - REACT_11057.2]
The aldosterone biosynthetic pathway is part of the Steroid Hormone Biosynthesis Pathway Suite. Click here to view the entire suite of related pathways. ...(less)
