Uth Biochemistry Block Iii Lecture 7

Front 1

Cholesterol has:
___Carbons
___Rings
and it is extremely:
hydrophobic OR hydrophilic?

Back 1

Cholesterol has:
27 Carbons
4 Rings
and it is extremely:
hydrophobic-- completely insoluble in water

Front 2

What are the four biological functions of cholesterol?

Back 2

1. modulate membrane fluidity
2. precursor for bile salts
3. precursor for steroid hormones
4. precursor for Vitamin D

Front 3

Cholesterol is obtained in the diet, but also can be synthesized in most cells. What is the major site for synthesis?

Back 3

Liver

Front 4

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?

Back 4

HMGCoA Synthase Isozymes:
1. Mitochondrial- makes ketone bodies
2. Cytosolic- cholesterol synthesis

Front 5

HMGCoA is reduced by what enzyme? This is a very important step in cholesterol synthesis. Also name the rxn.

Back 5

HMGCoA Reductase

HMGCoA + 2NADPH to Mevalonate (release 2NADP+ and CoA)

Front 6

HMGCoA Reductase is the rate limiting step of cholesterol synthesis and is reversible or irreversible?

Back 6

Irreversible, therefore committed

Front 7

HMGCoA Reductase is found in what part of the cell?

Back 7

Endoplasmic Reticulum; membrane associated and can "sense" hydrophobic compounds and fluidity of membrane environment

Front 8

HMGCoA Reductase is inhibited naturally by what?

Back 8

Feedback inhibition; Cholesterol (or by-product)

Front 9

HMGCoA Reductase is covalently modified for activity. Active as phosphorylated or dephosphorylated state? Answer should include Glucagon and Insulin.

Back 9

Phosphorylated (glucagon state) = inactive **you're not building products!!

Dephosphorylated (insulin state) = active **you can build because you are fed!!

Front 10

HMGCoA Reductase is also regulated at the (DNA, mRNA) level by what?

Back 10

mRNA is regulated (translation) by mevalonate derivative.

Front 11

HMGCoA reductase can be degraded. What is this stimulated by?

Back 11

Sterol derivatives.

Front 12

Lovastatin and Statins are ___ inhibitors used in management of cholesterol levels. What do they act on?

Back 12

Lovastatin and Statins are competitive inhibitors used in management of cholesterol levels.
They act on HMGCoA Reductase.

Front 13

___ is the 30 carbon precursor to cholesterol.

Back 13

Squalene; Review page 82

RXN bioenergetically irreversible because you release PPi

Front 14

Final conversion of squalene to cholesterol involves two main enzymes. They are ___ and ___.

Back 14

Squalene monooxygenase
Cyclase

Front 15

Monooxygenase is a mixed function oxidase meaning what for the oxygen?

Back 15

One oxygen atom will form the epoxide while the other will form water.

Front 16

Monooxygenase (a mixed function oxidase) involves what cofactor?

Back 16

cytochrome p450

Front 17

Where is this enzyme bound, i.e. what part of the cell?

Back 17

Endoplasmic Reticulum

Front 18

SREBP is Sterol Regulatory Element Binding Protein. It's precursor is bound to what membrane?

Back 18

Endoplasmic Reticulum

Front 19

At low cholesterol levels SREBP binds to what protein?

Back 19

SCAP- SREBP cleavage-activating protein

Front 20

SCAP bound to the SREBP facilitates what?

Back 20

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).

Front 21

At high cholesterol levels, SREBP is needed/not needed and what associates with SCAP that does not allow the SCAP-SREBP association?

Back 21

SREBP would NOT be needed with high cholesterol, so therefore SCAP-SREBP interaction is prevented with the binding of Insig-1 and Insig 2.

Front 22

SREBP is a nuclear transcription factor that activates genes that encode what?

Back 22

HMGCoA synthase, HMGCoA reductase, Farnesyl PP synthase, Squalene synthase, Lanosterol synthase and FA biosynthesis enzymes

Front 23

What are three things synthesized from cholesterol?

Back 23

Bile Salts
Steroid hormones
Vitamin D

Front 24

Which organ produces bile salts from cholesterol?

Back 24

Liver

Front 25

What is added to carbon 7 of cholesterol to make the first committed step in bile salt synthesis? What is the enzyme?

Back 25

alpha-hydroxyl group; enzyme is 7-alpha-hydroxylase

Front 26

Bile salts/acids are conjugated in amide linkage to the amino acids ___ and ___.

Back 26

glycine and taurine

Front 27

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?

Back 27

solubilize biliary cholesterol and prevent precipitation

route of excretion of cholesterol

Front 28

What is the rate limiting step in bile salt synthesis? And what inhibits/activates?

Back 28

Cholesterol 7-alpha-hydroxylase is the key rls and cholic acid inhibits (product) and cholesterol activates (substrate).

Front 29

Bile salts are the ionized form while bile acids are the protonated form. Name two primary bile acids.

Back 29

cholic acid and chenodeoxycholic acid

Front 30

Primary bile acids can be reduced by ___ to form secondary bile acids. Name the two secondary acids.

Back 30

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.

Front 31

90% of the bile acids are reabsorbed in the ___ and return to the ___ via what portal blood circulation?

Back 31

Reabsorbed in terminal ileum. Return to liver. Portal system is enterohepatic circulation.

Front 32

What bile acid is sulfated in the ___ and excreted on the second pass?

Back 32

Lithocholate is sulfated in the liver and secreted on the second pass (remember it is a secondary acid due to the bacteria).

Front 33

Unlike fat cholesterol can/can not be broken down and used for energy?

Back 33

CANNOT

Front 34

Bile salts that lack the 7-hydroxyl group are called ___.

Back 34

Secondary bile salts.