Regulation of Cholesterol synthesis
331 بار بازدید -
2 سال پیش
-
@Vips BiochemistryRegulation of Cholesterol synthesis
@Vips Biochemistry
Regulation of Cholesterol synthesis explains in detail the short term and long term regulation of the key rate limiting enzyme HMG CoA reductase. the gene regulation is illustrated with special animations to make the learning easier.
Allosterically inhibiting the key enzyme are Cholesterol itself, bile acids, Mevalonate
Statins group of drugs are having competitive inhibitory effect which will compete for the site on HMG CoA molecule. Statins attach to the same catalytic site and is found to alter the structure of the enzyme.
When ATP is in plenty, cholesterol production is not affected, this is common sense since high ATP indicate a fed state and availability of food and fuel. , but when AMP is high it induces modification of HMG CoA reductase through phosphorylation.
The unmodified dephosphorylated form of HMG CoA reductase is the active form.
The modified or phosphorylated form of HMG CoA reductase is inactive.
The hormones Glucagon and Epinephrine along with AMP and probably with sterols also involved,…they activate AMP dependent Protein kinase…., the enzyme for phosphorylation,… there by Phosphorylating the HMG CoA reductase….. so no more synthesis of cholesterol
On the other hand Insulin , the anabolic hormone,….it induces protein phosphatase which obviously,…dephosphorylates and activates HMG CoA reductase. We know that,… Insulin is produced at fed state when protein, fats and carbohydrates are available in plenty….and so cholesterol synthesis triggered….
STEROL REGULATORY ELEMENT BINDING PROTEIN – SREBP
SREBP Cleavage Activated Protein - SCAP
when cholesterol is available in high quantity, …it will act as regulatory molecule of itself
A high cholesterol level means, it will attach to SCAP on the membrane of ER. SREBP is associated with SCAP. SREBP has DNA binding domains on it …which should be released and attach to DNA for transcription of HMG CoA reductase gene.,….
BUT,.. upon activation of SCAP-SREBP complex, which occurs as a result of binding of cholesterol to SCAP,… the domain will not be released and now it will not go on to activate the gene for HMG CoA reductase on DNA. ….and no synthesis of cholesterol
On the other hand,… Low cholesterol level means there are no check on the SCAP and the SCAP-SREBP complex will now move to membrane of Golgi complex. In membrane of Golgi complex the proteins S1P and S2P are there, these proteins are responsible for releasing DNA binding domain on the complex ,…. and this DNA binding domain will eventually go on to bind the response element on target DNA namely SRE (Sterol Response Element), and trigger further transcription factors which is responsible for transcription of the HMG CoA reductase gene.
Regulation by proteolysis of the enzyme HMG CoA reductase is carried out by high amount of cholesterol itself. The catalytic domain which is exposed to cytoplasmic side of the enzyme will be acted upon by proteases upon induction by cholesterol and the enzyme is degraded.
Regulation of Cholesterol synthesis explains in detail the short term and long term regulation of the key rate limiting enzyme HMG CoA reductase. the gene regulation is illustrated with special animations to make the learning easier.
Allosterically inhibiting the key enzyme are Cholesterol itself, bile acids, Mevalonate
Statins group of drugs are having competitive inhibitory effect which will compete for the site on HMG CoA molecule. Statins attach to the same catalytic site and is found to alter the structure of the enzyme.
When ATP is in plenty, cholesterol production is not affected, this is common sense since high ATP indicate a fed state and availability of food and fuel. , but when AMP is high it induces modification of HMG CoA reductase through phosphorylation.
The unmodified dephosphorylated form of HMG CoA reductase is the active form.
The modified or phosphorylated form of HMG CoA reductase is inactive.
The hormones Glucagon and Epinephrine along with AMP and probably with sterols also involved,…they activate AMP dependent Protein kinase…., the enzyme for phosphorylation,… there by Phosphorylating the HMG CoA reductase….. so no more synthesis of cholesterol
On the other hand Insulin , the anabolic hormone,….it induces protein phosphatase which obviously,…dephosphorylates and activates HMG CoA reductase. We know that,… Insulin is produced at fed state when protein, fats and carbohydrates are available in plenty….and so cholesterol synthesis triggered….
STEROL REGULATORY ELEMENT BINDING PROTEIN – SREBP
SREBP Cleavage Activated Protein - SCAP
when cholesterol is available in high quantity, …it will act as regulatory molecule of itself
A high cholesterol level means, it will attach to SCAP on the membrane of ER. SREBP is associated with SCAP. SREBP has DNA binding domains on it …which should be released and attach to DNA for transcription of HMG CoA reductase gene.,….
BUT,.. upon activation of SCAP-SREBP complex, which occurs as a result of binding of cholesterol to SCAP,… the domain will not be released and now it will not go on to activate the gene for HMG CoA reductase on DNA. ….and no synthesis of cholesterol
On the other hand,… Low cholesterol level means there are no check on the SCAP and the SCAP-SREBP complex will now move to membrane of Golgi complex. In membrane of Golgi complex the proteins S1P and S2P are there, these proteins are responsible for releasing DNA binding domain on the complex ,…. and this DNA binding domain will eventually go on to bind the response element on target DNA namely SRE (Sterol Response Element), and trigger further transcription factors which is responsible for transcription of the HMG CoA reductase gene.
Regulation by proteolysis of the enzyme HMG CoA reductase is carried out by high amount of cholesterol itself. The catalytic domain which is exposed to cytoplasmic side of the enzyme will be acted upon by proteases upon induction by cholesterol and the enzyme is degraded.
2 سال پیش
در تاریخ 1401/02/07 منتشر شده
است.
331
بـار بازدید شده