Regulation of cholesterol supply for mineralocorticoid biosynthesis.

Cortisol also promotes epinephrine synthesis in the medulla. Produced in the cortex, cortisol reaches the adrenal medulla and at high levels, the hormone can promote the up regulation of phenylethanolamine N-methyltransferase (PNMT), thereby increasing epinephrine synthesis and secretion.

Regulation of steroid hormone biosynthesis by the cytoskeleton.

Therefore, physiological glucocorticoid synthesis and release largely matches that of ACTH.

Regulation of Aldosterone Synthesis and Secretion.

Sphingosine‐1‐phosphate rapidly increases cortisol biosynthesis and the expression of genes involved in cholesterol uptake and transport in H295R adrenocortical cells.

Regulation of Aldosterone Synthesis and Secretion

Involvement of protein kinase C and cyclic adenosine 3′,5′‐monophosphate‐dependent kinase in steroidogenic acute regulatory protein expression and steroid biosynthesis in Leydig cells.

The liver plays a central role in regulation of the body's cholesterol homeostasis.

Cholesterol acts as the precursor for the synthesis of ..

Individuals with genetic deficiencies in the conversion of cholesterol to bile acids are treated with exogenously supplied chenodeoxycholic acid.

Figure 18.9 Synthesis of the bile acids, cholic acid and chenodeoxycholic acid, from cholesterol.

Bile salts provide the only significant mechanism for cholesterol excretion, both as a metabolic product of cholesterol and as a solubilizer of cholesterol in bile.

D.

The synthesis of these hormones starts with cholesterol

Synthesis of bile acids
Bile acids are synthesized in the liver by a multistep, multiorganelle pathway in which hydroxyl groups are inserted at specific positions on the steroid structure; the double bond of the cholesterol B ring is reduced; and the hydrocarbon chain is shortened by three carbons, introducing a carboxyl group at the end of the chain.

REGULATION OF CHOLESTEROL SYNTHESIS • Controlled by HMG CoA ..

This results in the retention of the SCAP—SREBP complex in the ER, thereby preventing the activation of SREBP-2, and leading to downregulation of cholesterol synthesis.

Approximately 0.5 g/day is synthesized from cholesterol in the liver to replace the amount lost.

Cholesterol: Synthesis, Metabolism, Regulation

It also decreases synthesis of the reductase by preventing expression of its gene as seen with the LDL receptor.] ACAT = acyl CoA:cholesterol acyltransferase; HMG CoA = hydroxymethylglutaryl coenzyme A; mRNA = messenger RNA.
E.

The control by angiotensin II of cholesterol supply for aldosterone biosynthesis.

Biosynthesis of Lipids | Cholesterol | Biosynthesis

Angiotensin II‐induced mitogen‐activated protein kinase phosphatase‐1 expression in bovine adrenal glomerulosa cells: Implications in mineralocorticoid biosynthesis.

Potassium channel mutant KCNJ5 T158A expression in HAC‐15 cells increases aldosterone synthesis.

To synthesize aldosterone, cholesterol is ..

[Note: Cholesterol stones account for over 85% of cases of cholelithiasis, with bilirubin and mixed stones accounting for the rest].
Figure 18.12 Gallbladder with gallstones.


Objectives - Choleterol Biosynthesis
Describe
cholesterol synthesis
explaining the importance of pyrophosphates, farnesyl pyrophosphate & geranylgeranyl pyrophosphate, inhibition of HMG CoA reductase with statins, and resulting change in LDL levels.