CB Quiz 2 Flashcards
What enzyme is mainly responsible for Cholesterol Synthesis
Acetyl Coenzyme A (Acetyl CoA)
What is the main source of transport for Cholesterol?
How is it taken up in cells?
LDLs
Specific surface receptors
Describe the Structure of Cholesterol
Made up of a steroid nucleus with a condensed 4 ring structure
Attached to a hydrocarbon chain
Low H2O solubility
Explain the full Process of Cholesterol Synthesis
Cholesterol is synthesized from Acetyl CoA enzyme in 3 stages
- Synthesis of Isopentenyl Pyrophosphate from Mevalonate (in 3 consecutive reactions requiring ATP)
- Condensation of six molecules of Isopentenyl Pyrophosphate to form Squalene (C5 -> C10 -> C15 - C30)
- Squalene cyclizes and the tetracyclic product is converted to cholesterol (first changes to Squalene 2,3-epoxide, which undergoes cyclization to form Lanosterol which is then converted to Cholesterol by multiple reactions)
=> Mevalonate -> Isopentenyl -> Squalene ->Squalene 2,3-epoxide -> Lanosterol -> Cholesterol
What’re the 2 main ways cholesterol can be obtained
Diet (Exogenous)
Synthesized in the body (Endogenous)
Endogenous
Synthesized in the body
Exogenous
Obtained in diet
What are the major sites of cholesterol synthesis? Can it, generally speaking, be produced in any cell?
All nucleated cells are capable of synthesis but the major sites are the Liver, Intestine, Reproductive Tissue, and Adrenal Glands.
So no, not every cell… every nucleated cell lmao
Statins
Class of drugs that inhibit cholesterol Synthesis
Brownie points: Inhibits HMG CoA Reductase
LEARNING OUTCOME: Describe the Physiological Regulation of Cholesterol in the body
The rate of cholesterol formation in the body is highly responsive to cellular levels of cholesterol. This is controlled by the negative feedback mechanism mediated primarily by changes in its amount in the body and the activity of
3-Hydroxy-3-Methylglutaryl CoA Reductase (HMG CoA Reductase) which is inhibited by Statins.
Control of HMG CoA Reductase:
• Rate of Synthesis of Reductase mRNA is controlled by the sterol regulatory element binding protein (SREBP). When cholesterol levels are low, this transcription factor induces transcription of HMG CoA Reductase.
• Rate of Translation of Reductase mRNA is inhibited by Nonsterol Metabolites derived from Mevalonate and dietary cholesterol.
• Degredation of the Reductase due to increased levels of cholesterol.
• Phosphorylation decreases the activity of the Reductase in response to low levels of ATP
LEARNING OUTCOME: Describe the Pharmacological Regulation of Cholesterol
Pharmacological Regulation of Cholesterol:
1. Statins: Inhibition of in vivo synthesis of cholesterol in the liver (by inhibiting HMGCoA Reductase)
2. Cholestyramine/Colestipol: Reduces Bile Acids in the intestine which reduces absorption of Exogenous cholesterol and increases the metabolism of Endogenous cholesterol into bile acids
3. PCSK9 Inhibitors: Reduces circulating LDL. PCSK9 enhances the number of LDL receptors across tissues (given to patients intolerant of Statin)
These methods proved to decrease cardiovascular-related mortality among patients with high LDL presence in their blood.
Describe the role of the drug Colestipole
Reduces Bile Acids in the Intestines which reduces absorption of Exogenous cholesterol and increases the metabolism of Endogenous Cholesterol into bile acids
What is the Role of PCSK9?
PCSK9 enhances the number of LDL Receptors across tissues
When are PCDK9 inhibitors prescribed?
When the patient is intolerant of Statin
What are the main derivatives of Cholesterol?
Bile Acids
Bile Salts
Steroid Hormones
Vitamin D
What is the significance of Bile Salts and Bile Acids in terms of cholesterol regulation.
Their production eliminates cholesterol from the body by converting it into Bile
Where is Bile synthesized
Liver
Where is bile stored and secreted? Where is it secreted to?
Stored in the gall-bladder
Secreted through the bile duct
Secreted into the small intestine (Duodenum)
What is the primary function of Bile Acids
Bile acids are amphipathic molecules which allows them to emulsify triglycerides in the small itnestine
How are Bile Salts produced?
What is their main function?
What happens when bile salts are exposed to the Bacterial Flora of the intestine
Produced in the liver, bile salts are made through conjugating bile acids with either Glycine or Taurine.
The main function of Bile Salt is being a detergent
When Bile Salts are exposed to Bacterial Flora of the intestine:
- Aids in the regeneration of Bile Acids (from the removal of glycine or Taurine) and production of Secondary Bile Salts (removal of OH group)
What is Cholelithiases?
How is it treated?
Occurs due to lack of bole salts being secreted to handle the amount of cholesterol present. It is caused by either:
malabsorption of bile acids
Biliary tract obstruction
Lack of Melatonin
This condition results in cholesterol precipitates in the Gall-Bladder
Cholecystectomy is the removal of the gall bladder (Treatment)
What are the steroid hormones that are derived from Cholesterol?
Progesterone Androgens Estrogens Glucocorticoids Mineralocorticoids
Progesterone
Prepares the lining of the uterus for implantation of an ovum and maintenance of pregnancy
Androgens
Responsible of the development of male characteristics