Cholesterol is first changed to form pregnenolone (common pathway). For this free cholesterol is released in the cytosol from cholesteryl esters of cytoplasmic lipid droplets and transferred into mitochondria. An enzyme called "cytochrome-P- 450-sidechain cleavage" enzyme (P450 sce) present in inner mitochondrial membrane hydroxylates cholesterol at C22 and C20 (also called "20, 22-desmolase") and then cleaves the side chain to form pregnenolone and isocaproic aldehyde. The enzyme requires molecular O2 and NADPH like all mono-oxygenases and also require FAD-containing Fp, a Fe2S2 protein (called adreno- doxin). Pregnenolone to 17-OH pregnenolone: Pregnenolone is transferred to smooth endoplasmic reticulum (ER), where it is conveed to 17-OH-pregneno- lone catalysed by the enzyme 17-aaa-hydroxylase. * Conversion of 17-OH pregnenolone to 17-OH progesterone: This is achieved by two enzymes, one is NAD+ dependent 3 bbb-OH-steroid dehydrogenase and the other is DDD4,5-isomerase. Alternatively, the same pregnenolone may be first conveed to 'progesterone' by the action of the two enzymes dehydrogenase and isomerase and it is acted upon by the enzyme 17-a-hydroxylase to form 17-OH progesterone. PROGESTERONE * Progesterone is the hormone of the corpus luteum, the structure which develops in the ovary from the ruptured Graafian follicle. It is also formed by the placenta, which secretes progesterone, during the later pa of pregnancy. Progesterone is also formed in the adrenal coex, as a precursor of both C19 and C21 coicosteroids. It is also formed in the testes. Chemistry: Progesterone may be regarded as a derivative of "pregnane" and is designated chemically as "4- pregnane-3, 20-dione". It is a C21 steroid and has a - CH3 group at C10 and C13. Biosynthesis: Progesterone has a role as an intermediate in the biogenesis of adrenocoical hormones and of androgens. Indirectly androstenedione and testosterone, it also serves as precursors for estrogens also. Progesterone is formed from acetate cholesterol, 'Pregnenolone' is the immediate precursor. Mechanism of action: It is similar to estrogen.Ref: Textbook of Medical Biochemistry, Eighth Edition, Dr (Brig) MN Chatterjea, page no: 590-591,603-604