Cholesterol Biosynthesis, Transport and Genetics Flashcards
What is cholesterol required as a precursor for
-vitamin D
-steroids
-bile salts
what molecule is a major structural component in myelin sheaths
cholesterol
what synthesizes myelin sheaths (In PNS and CNS)
glial cells
PNS- Schwann cells
CNS- oligodenrocytes
what molecule produces cholesterol
acetyl CoA
describe the chemical structure of steroids
4 hydrocarbon rings
describe the cholesterol chemical structure
4 hydrocarbon rings with a hydrocarbon tail and a hydrophilic region
where is cholesterol synthesized
mainly the liver and small intestine, also in adrenal glands and gonads
how much cholesterol does an average adult synthesize daily
800 mg
what are the levels for desirable and high total cholesterol
-desirable: under 200
- high: over 240
what are the good and high levels of LDL cholesterol
good: 100-120
high: 160-190
what are the good and undesirable levels of HDL cholesterol
good: over 60
undesirable: under 40
what are the 3 stages in de novo biosynthesis of cholesterol
- synthesis of isopentenyl phosphate
- condensation of 6 molecules of isopentyl pyrophosphate to form squalene
- cyclization of squalene to form the steroid 4-ring structure, which rearranges to form ianosterol which is then converted into cholesterol
explain the first step of de novo biosynthesis of cholesterol in detail
acetoacetyl CoA combines with acetyl CoA to form HMG CoA. HMG CoA is converted to mevalonate in the cytosol by HMG CoA reductase. mevalonate is then converted into isopentyl pyrophosphate
what is the rate limiting step in the regulation of cholesterol biosynthesis
the production of mevalonate from HMG-CoA by HMG CoA reductase
what is HMG CoA reductase
enzyme that catalyzes the first step of cholesterol biosynthesis. it is tightly regulated at the transcriptional and translational levels
what is the rate of synthesis of reductase mRNA controlled by
a transcription factor called sterol regulatory element bind protein (SREBP)
how does SREBP work
it is regulated by levels of cholesterol available by the INSIG and SCAP proteins that bind cholesterol
what is the rate of translation of reductase mRNA inhibited by
metabolites derived from mevalonate and dietary cholesterol
what is the degradation of reductase tightly controlled by
lanosterol
where is the SREBP, SCAP, and insig protein complex located when they stay together
ER membrane
where is the SREBP and SCAP complex located when it dissociates from INSIG
golgi
what do lanosterol and acetyl CoA carboxylase have in common
they catalyze a similar step in their respective pathways (cholesterol biosynthesis and fatty acid biosynthesis) and are switched off by a AMP activated protein kinase. their processes cease when ATP is low
what are the drugs that regulate cholesterol synthesis
stains and bisphosphonates
how do statins work
competitively inhibiting HMG CoA reductase thus reducing the amount of mevalonate produced
when does cholesterol synthesis occur
at night
what is the extra benefit of statins
inhibit bone resorption by osteoclasts because they also inhibit prenylated proteins
what is necessary in the diet to absorb dietary cholesterol
fat
what are bisphosphonates used for
treating bone disorders to inhibit osteoclast resorption of bone
what is a side effect os bisphosphonates
osteonecrosis of jaw
what part of the de novo pathway for cholesterol biosynthesis do bisphosphonates work
the isopentenyl-5-prophosphate
what happens in protein prenylation
post translational modification of proteins that adds a hydrophobic molecule to target proteins that anchors the protein to the membrane surface
describe the role of prenylation is osteoclast function
small GTPase localize to specific membrane compartments and assist in cytoskeleton rearrangement needed to form the sealing zone
where are bile and bile salts made and stored
they are made in the liver and stored in the gallbladder
when does the gallbladder release bile
after we eat and fat is present in the digestive tract
what are functions of bile and bile salts
- aid digestion by breaking down fats
-help absorb fat-soluble vitamins
-eliminate waste products
what is bile composed of
water, lecithin, bile salts and cholesterol
what is the major way that cholesterol is eliminated from the body
bile salts
how does the amphipathic nature of bile salts contribute to their function
emulsification of lipid aggregates and solubilization and transport of lipids in an aqueous environment
