Cholesterol Biosynthesis Flashcards
Cholesterol has a crucial role in the structure of ____
Membranes
What is cholesterol a precursor for?
Steroid hormones and bile salts
Why is cholesterol not required in the diet?
Because all cells can synthesize cholesterol from simple precursors
What is Smith-Lemli Opitz Syndrome?
Syndrome with multiple malformations and mental disability associated with defective cholesterol biosynthesis due to defective enzyme in final step of cholesterol synthesis pathway
Although all cells can synthesize cholesterol, where is it primarily made?
The liver
What is the fate of cholesterol produced by the liver?
Small amount incorporated into hepatocyte membranes, most exported
What compound is cholesterol made of?
Acetyl coA (4)
What is the rate limiting step of cholesterol synthesis?
reduction of HMG-CoA to mevalonate by HMG-CoA reductase
What enzymes do statins inhibit?
HMG-CoA Reductase
How is HMG-CoA reductase regualted at the level of the enzyme?
- Cholesterol inhibits the enzyme allosterically via feedback inhibition
- Cholesterol and cholesterol derivatives promote rapid degradation of the enzyme via ubiquitin/proteasome
How is HMG-CoA reductase regulated at the level of the genome?
- Cholesterol can inhibits its own transcription in the nucleus
Describe the hormonal regulation of HMG-CoA reductsae.
- The enzyme is inhibited when it is phosphorylated.
- Glucagon –> stimultes kinase –> phosphorylates HMG-CoA reductase –> inhibited
- Insulin –> stimulates phosphatase –> removes phosphate –> HMG-CoA reductsae active
What enzyme is responsible for esterifying cholesterol?
Acyl-CoA-Cholesterol Acyl Transferase (ACAT)
What happens to newly formed cholesterol in the liver?
It is esterified and packed into VLDL
What is the purpose of esterifying cholesterol?
Makes it less polar so it is able to enter lipid droplet
Bile salts are made in the ____ and secreted into the ____
Liver
Gallbladder
What do bile salts do?
They are detergents - they are able to solubilize lipids b/c they have both non-polar and polar groups (amphipathic). All the polar groups are in the same plane, creating separation of polar and non-polar areas. This causes them to form micelles in solution.
Primary bile salts are made by the body. What are secondary bile salts?
Gut bacteria can act on primary bile salts to make secondary bile salts
What is the difference between a bile acid and bile salt?
Although many use them interchangeabley, a bile acid is what is made by the body and a bile salt is a bile acid conjugated with amino acids.
Describe the recycling of bile salts.
- Synthesized liver –> stored gallbaldder –> released to intestines when needed –> active transport of bile salts from ileum back to liver
- Some bile salt spillsover to systemic circulation and is excreted in the kidney, so there is some need to synthesize new bile salts daily but not much as most is recycled
Is vitamin D a hormone?
Yes - it is produced at one site, transported through blood and exerts its effects at distant site –> HORMONE
Vitamin D deficiency is called ____ in children and ____ in adults
Rickets
Osteomalacia
Vitamin D is formed in the ______ from ______
Skin
Cholesterol
What are the effects of Vitamin D on the:
- Intestine
- Bone
- Kidney
- Absorb calcium
- Promote calcification of bone
- Increase resorption of Ca2+ from kidney
What are the 4 basic steps of cholesterol synthesis?
Which step of cholesterol synthesis is the committed step?
Formation of acetoacetyl coA by thiolase
The cytosolic HMG-CoA synthase in the cholesterol biosynthesis pathway is (the same/different) from the HMG-coA synthase in the mitochondria used for ketone body formation.
Different isozyme
