Sterol-dependent regulation of gene expression
-HMG CoA reductase expression is controlled by transcription factor SREBP-2 that binds DNA at the cia-acting sterol regulatory element (SRE) upstream of reductase gene
-SREBP-2 is an integral protein of ER membrane and associates with a second protein SCAP
-When sterol levels are low in cell, SREBP-SCAP complex moves from ER to GA
-SREBP-2 is subsequently acted upon by 2 proteases which generate a soluble fragemnt that enters the nucleus, binds SRE, and functions as a transcription factor
-Results in increased cholesterol synthesis
-Abundant sterols= they bind SCAP at it's sterol sensing domain and insigs (insulin induced gene)
-This down regulates cholesterol synthesis
-SREBP-1 upregulates expression of enzymes involved in fatty acid synthesis in response to insulin
Synthesis of bile acids
-In the liver
-Double bond of the cholesterol B ring is reduced
-Hydrocarbon chain is shortened by three carbons, introducing a carboxyl group at the end of the chain.
In autosomal dominant familial hypercholesterolemia, where the abnormal allele encodes a dysfunctional LDL receptor, cholesterol synthesis is less responsive to plasma cholesterol levels.
Cholesterol: Synthesis, Metabolism, Regulation
The steroidal hormones are all derived from cholesterol and circulating LDL particles in the blood stream. is made in the liver and then is used to make pregnenolone, which is the primary "master" steroidal hormone. Without adequate cholesterol or LDL, steroidal hormone production can be significantly impaired.
And these type of hormones are lipids that are made from cholesterol
Thyroid Stimulating Hormone (TSH): A pituitary hormone that triggers release of (T4) and (T3) from the thyroid gland, both of which play key roles in determining the body's metabolic rate and temperature, rate of protein synthesis and sensitivity to a class of substances called the best known example being the neurotransmitter/hormone or . TSH is inhibited by somatostatin.
soluble hormones are derived from cholesterol
The first committed step in steroid biosynthesis is the conversion of the 27-carbon skeleton of cholesterol to a C21-compound, pregnenolone (). This critical step, which is subject to hormonal control by the adrenocorticotropic hormone (ACTH) in the adrenals and by the luteinizing hormone (LH) in the gonads, is catalysed by a P-450 enzyme, the cholesterol side-chain cleavage enzyme P-450scc (also called 20,22-desmolase, or 20,22-lyase). Pregnenolone can be converted either to progesterone, which branches to the glucocorticoid and androgen/estrogen pathways, or to 17α-hydroxypregnenolone, which is another route for the formation of androgens and estrogens (, top-left part). Androgen formation in the adrenals is limited to dehydroepiandrosterone and androstenedione, whereas in the testes the presence of 17ß-hydroxysteroid dehydrogenase (17HSD) in Leydig cells (under the control of LH) ensures the formation of testosterone, the principal " male " hormone. Estrogen formation requires another P-450 enzyme, the aromatase complex (P-450Arom). The substrate is either androstenedione (for estrone) or testosterone (for estradiol). Estrone and estradiol are interconvertible through a reversible reaction involving another 17ß-hydroxysteroid dehydrogenase, as in the androstenedione-testosterone conversion. Aromatase activity is present in the ovary and the placenta (see below). In the ovary, aromatase activity and estrogen formation occur in cells and are controlled by the follicle-stimulating hormone (FSH), whereas production of the androgenic substrates (testosterone, 4-androstenedione) requires LH stimulation of the cells (5).
What hormone is synthesized from cholesterol
Sterol-accelerated enzyme degradation
-HMG CoA reductase activity is controlled covalently through actions of AMP activated protein kinase & phosphoprotein phosphatase
-Phosphorylated form of the enzyme is inactive
-Desphosphorylated form is active
-AMPK is activated by AMP, cholesterol synthesis, like fatty acid synthesis, is decreased when ATP availability is decreased