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Pregnenolone biosynthesis
Stable Identifier
R-HSA-196108
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
Locations in the PathwayBrowser
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Metabolism (Homo sapiens)
Metabolism of lipids (Homo sapiens)
Metabolism of steroids (Homo sapiens)
Metabolism of steroid hormones (Homo sapiens)
Pregnenolone biosynthesis (Homo sapiens)
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The first process in the synthesis of all steroid hormones is the synthesis of pregnenolone from cholesterol. In this process, cholesterol mobilized from cytosolic lipid droplets or from lysosomes is transported to mitochondria and becomes localized to the inner mitochondrial membrane. Cholesterol transport appears to be rate-limiting for steroid hormone synthesis and its regulation, at the step of StAR-mediated traversal of the mitochondrial membrane, plays a central role in determining the amounts and identities of steroid hormones made in the body. In the inner mitochondrial membrane, cholesterol is converted to pregnenolone in a sequence of three reactions, all catalyzed by CYP11A (side chain cleavage enzyme). Finally, pregnenolone re-enters the cytosol (Payne and Hales 2004; Stocco 2001).
Literature References
PubMed ID
Title
Journal
Year
11181954
StAR protein and the regulation of steroid hormone biosynthesis
Stocco, DM
Annu Rev Physiol
2001
15583024
Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones
Payne, AH
,
Hales, DB
Endocr Rev
2004
Participants
Events
CHOL translocates from cytosol to mitochondrial intermembrane space
(Homo sapiens)
Cholesterol translocates from mitochondrial intermembrane space to inner mitochondrial membrane
(Homo sapiens)
TSPO:BZRAP1 transports CHOL from outer mitochondrial membrane to inner mitochondrial membrane
(Homo sapiens)
Oxidation of cholesterol to 22beta-hydroxycholesterol
(Homo sapiens)
Oxidation of 22beta-hydroxycholesterol to 20alpha,22beta-hydroxycholesterol
(Homo sapiens)
CYP11A1 cleaves 20a,22b-DHCHOL
(Homo sapiens)
Translocation of isocaproaldehyde from the mitochondrial matrix to the cytosol
(Homo sapiens)
Reduction of isocaproaldehyde to 4-methylpentan-1-ol
(Homo sapiens)
Pregnenolone translocates from the mitochondrial matrix to the cytosol
(Homo sapiens)
Participates
as an event of
Metabolism of steroid hormones (Homo sapiens)
Event Information
Go Biological Process
C21-steroid hormone biosynthetic process (0006700)
Orthologous Events
Pregnenolone biosynthesis (Bos taurus)
Pregnenolone biosynthesis (Caenorhabditis elegans)
Pregnenolone biosynthesis (Canis familiaris)
Pregnenolone biosynthesis (Danio rerio)
Pregnenolone biosynthesis (Dictyostelium discoideum)
Pregnenolone biosynthesis (Drosophila melanogaster)
Pregnenolone biosynthesis (Gallus gallus)
Pregnenolone biosynthesis (Mus musculus)
Pregnenolone biosynthesis (Rattus norvegicus)
Pregnenolone biosynthesis (Saccharomyces cerevisiae)
Pregnenolone biosynthesis (Schizosaccharomyces pombe)
Pregnenolone biosynthesis (Sus scrofa)
Pregnenolone biosynthesis (Xenopus tropicalis)
Authored
Jassal, B (2008-10-01)
Reviewed
D'Eustachio, P (2007-04-21)
Created
D'Eustachio, P (2007-04-17)
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