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34 Cards in this Set

  • Front
  • Back
Cholesterol has:
and it is extremely:
hydrophobic OR hydrophilic?
Cholesterol has:
27 Carbons
4 Rings
and it is extremely:
hydrophobic-- completely insoluble in water
What are the four biological functions of cholesterol?
1. modulate membrane fluidity
2. precursor for bile salts
3. precursor for steroid hormones
4. precursor for Vitamin D
Cholesterol is obtained in the diet, but also can be synthesized in most cells. What is the major site for synthesis?
Review cholesterol biosynthesis on page 80-82. There are two isozymes for HMGCoA synthase. Where in the cell are these produced and what are the differing functions?
HMGCoA Synthase Isozymes:
1. Mitochondrial- makes ketone bodies
2. Cytosolic- cholesterol synthesis
HMGCoA is reduced by what enzyme? This is a very important step in cholesterol synthesis. Also name the rxn.
HMGCoA Reductase

HMGCoA + 2NADPH to Mevalonate (release 2NADP+ and CoA)
HMGCoA Reductase is the rate limiting step of cholesterol synthesis and is reversible or irreversible?
Irreversible, therefore committed
HMGCoA Reductase is found in what part of the cell?
Endoplasmic Reticulum; membrane associated and can "sense" hydrophobic compounds and fluidity of membrane environment
HMGCoA Reductase is inhibited naturally by what?
Feedback inhibition; Cholesterol (or by-product)
HMGCoA Reductase is covalently modified for activity. Active as phosphorylated or dephosphorylated state? Answer should include Glucagon and Insulin.
Phosphorylated (glucagon state) = inactive **you're not building products!!

Dephosphorylated (insulin state) = active **you can build because you are fed!!
HMGCoA Reductase is also regulated at the (DNA, mRNA) level by what?
mRNA is regulated (translation) by mevalonate derivative.
HMGCoA reductase can be degraded. What is this stimulated by?
Sterol derivatives.
Lovastatin and Statins are ___ inhibitors used in management of cholesterol levels. What do they act on?
Lovastatin and Statins are competitive inhibitors used in management of cholesterol levels.
They act on HMGCoA Reductase.
___ is the 30 carbon precursor to cholesterol.
Squalene; Review page 82

RXN bioenergetically irreversible because you release PPi
Final conversion of squalene to cholesterol involves two main enzymes. They are ___ and ___.
Squalene monooxygenase
Monooxygenase is a mixed function oxidase meaning what for the oxygen?
One oxygen atom will form the epoxide while the other will form water.
Monooxygenase (a mixed function oxidase) involves what cofactor?
cytochrome p450
Where is this enzyme bound, i.e. what part of the cell?
Endoplasmic Reticulum
SREBP is Sterol Regulatory Element Binding Protein. It's precursor is bound to what membrane?
Endoplasmic Reticulum
At low cholesterol levels SREBP binds to what protein?
SCAP- SREBP cleavage-activating protein
SCAP bound to the SREBP facilitates what?
Cleavage at site 1, which allows the SREBP precursor to cleave at site 2 which releases the SREBP peptide (from the N-terminal end in the cytoplasm).
At high cholesterol levels, SREBP is needed/not needed and what associates with SCAP that does not allow the SCAP-SREBP association?
SREBP would NOT be needed with high cholesterol, so therefore SCAP-SREBP interaction is prevented with the binding of Insig-1 and Insig 2.
SREBP is a nuclear transcription factor that activates genes that encode what?
HMGCoA synthase, HMGCoA reductase, Farnesyl PP synthase, Squalene synthase, Lanosterol synthase and FA biosynthesis enzymes
What are three things synthesized from cholesterol?
Bile Salts
Steroid hormones
Vitamin D
Which organ produces bile salts from cholesterol?
What is added to carbon 7 of cholesterol to make the first committed step in bile salt synthesis? What is the enzyme?
alpha-hydroxyl group; enzyme is 7-alpha-hydroxylase
Bile salts/acids are conjugated in amide linkage to the amino acids ___ and ___.
glycine and taurine
Bile salts are stored in the gallbladder and released durign a meal to aid in lipid digestion. What are the other two functions of bile salts?
solubilize biliary cholesterol and prevent precipitation

route of excretion of cholesterol
What is the rate limiting step in bile salt synthesis? And what inhibits/activates?
Cholesterol 7-alpha-hydroxylase is the key rls and cholic acid inhibits (product) and cholesterol activates (substrate).
Bile salts are the ionized form while bile acids are the protonated form. Name two primary bile acids.
cholic acid and chenodeoxycholic acid
Primary bile acids can be reduced by ___ to form secondary bile acids. Name the two secondary acids.
Reduction is done be colonic bacteria. They removed 7-alpha-hydroxy group to form secondary bile acids. Cholic acid becomes deoxycholic acid and chenodeoxycholic acid becomes lithocholic acid.
90% of the bile acids are reabsorbed in the ___ and return to the ___ via what portal blood circulation?
Reabsorbed in terminal ileum. Return to liver. Portal system is enterohepatic circulation.
What bile acid is sulfated in the ___ and excreted on the second pass?
Lithocholate is sulfated in the liver and secreted on the second pass (remember it is a secondary acid due to the bacteria).
Unlike fat cholesterol can/can not be broken down and used for energy?
Bile salts that lack the 7-hydroxyl group are called ___.
Secondary bile salts.