Which of the following is considered the regulated step in steroid hormone synthesis in the zona fasciculata?
Correct Answer: Cholesterol to pregnenolone
Description: The conversion of cholesterol to pregnenolone is considered the rate-limiting and regulated step in steroid biosynthesis in the zona fasciculata, which secretes the glucocoicoid, coisol. ACTH binds to a membrane-associated receptor and increases cAMP formation. The subsequent activation of protein kinases and phosphorylation results in increased expression of LDL receptors and activation of cholesterol esterase. The increase in LDL receptors increases the delivery of cholesterol to the zona fasciculata. The activation of cholesterol esterase increases the liberation of intracellular cholesterol from cholesterol esters. ACTH also induces a mitochondrial protein called steroidogenic acute regulatory (StAR) protein. StAR functions to shuttle cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane, where the cholesterol side chain cleavage enzyme conves it to pregnenolone. Also Know: Coicosterone is conveed to aldosterone in the zona glomerulosa, but not in the zona fasciculata. This is also a regulated step. Angiotensin II acts a membrane-associated receptor to increase the activity of aldosterone synthase (a combination of two enzymes with 18b-hydroxylase activity) and, hence, increase aldosterone synthesis and secretion. 11-deoxycoisol is conveed to coisol primarily in the zona fasciculata, but also in the zona reticularis. The enzyme responsible is 11b-hydroxylase, a mitochondrial enzyme. 11b-hydroxylase is not regulated by ACTH. Pregnenolone is conveed to progesterone in all steroid secreting tissues. The enzymes responsible are 3b-ol dehydrogenase and D4,5-isomerase. These enzymes are cytoplasmic, and are not regulated by ACTH. Ref: Weil P. (2011). Chapter 41. The Diversity of the Endocrine System. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds),Harper's Illustrated Biochemistry, 29e.
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Biochemistry
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