Biochemistry - Cholesterol and Fat Soluble Vitamins

Question 1

What is the ratio of cholesterol:sphingolipid in lipid rafts?

Answer 1

~1:1

Question 2

Name four important cholesterol derivatives.

Answer 2

Bile salts, steroid hormones, Vitamin D, coenzyme Q

Question 3

Where do we get cholesterol?

Answer 3

Synthesis and from diet (animal products only - can’t use plant sitosterols)

Question 4

What enzyme is involved in the major regulatory step in cholesterol synthesis?

Answer 4

HMG coA reductase.

Question 5

Describe how HMG coA reductase is regulated.

Answer 5

• Statins inhibit (they mimic cholesterol and bind to allosteric site on enzyme).
• Free cholesterol inhibits allosterically, as well as increases enzyme degradation and decreases transcription of the enzyme gene.
• Glucagon and epinephrine inhibit via phosphorylation.

Question 6

How many carbons is an isoprene unit (IPP)?

Answer 6

5

Question 7

In cholesterol synthesis, what intermediate is created when three IPP units are combined? What important molecules are made from this intermediate?

Answer 7

Farnesyl pyrophosphate (FPP) - 15 carbons. Dolichol and ubiquinone are made from this.

Question 8

What is the enzyme 7-alpha hydroxylase involved in?

Answer 8

Synthesis of bile salts. It adds a hydroxyl group to carbon #7 and —> bile salts!

Question 9

Does the re-uptake of bile salts from the enterohepatic circulation require energy?

Answer 9

Yeah.

Question 10

What is the carrier of steroid hormones in the blood?

Answer 10

Albumin.

Question 11

Do steroid hormones activate intracellular second messengers or do they alter gene transcription?

Answer 11

Alter gene transcription because they are hydrophobic enough to pass through membranes and into the nucleus to bind to transcription factors.

Question 12

Name the four fat-soluble vitamins.

Answer 12

A, D, E, K

Question 13

Can the fat soluble vitamins be excreted in urine?

Answer 13

Nope

Question 14

What are the three types of Vitamin A?

Answer 14

Retinal, retinol, retinoic acid.

Question 15

What are the sources of vitamin A?

Answer 15

Carotinoids - must be cleaved to get vitamin A (carotinoid is basically two vitamin A’s linked head-to-tail)

Question 16

What is retinoic acid involved in?

Answer 16

Important in growth and differentiation.

Question 17

What is retinal involved in? Describe the process.

Answer 17

Involved in vision. Retinal combines with opsin protein to make rhodopsin. Light hits that, and induces a cis –> trans isomerization. The conformational change is the first signal in vision.

Question 18

What results from vitamin A deficiency?

Answer 18

Night blindness

Question 19

What is the immediate precursor in Vitamin D synthesis?

Answer 19

The penultimate product of cholesterol synthesis: 7-dehydrocholesterol.

Question 20

Which three organs are involved in vitamin D synthesis and what are their respective intermediate products?

Answer 20

Skin makes D3, liver makes 25-hydroxycholecalciferol, kidney makes 1,25-hydroxycholecalciferol (most active form of vitamin D)

Question 21

What does a healthy amount of vitamin D do?

Answer 21

Promotes interstitial Ca2+ absorption and bone formation.

Question 22

What results from vitamin D deficiency? What results from toxicity?

Answer 22

Deficiency: poor mineralization of bones (Rickets)

Toxicity: Brittle bones - high vitamin D tells the body to get more Ca2+ in the serum, so calcium is resorbed from the bones. Also leads to renal stones and metastatic calcifications.

Question 23

What is an important function of vitamin E?

Answer 23

It is an antioxidant and terminates free radical oxidation of unsaturated fatty acids.

Question 24

What is vitamin K used for?

Answer 24

Gamma carboxylation of glutamate residues on prothrombin, so it can attach to the membrane for cleavage.

Question 25

What enzymes are involved in gamma carboxylation of glutamate?

Answer 25

Vitamin K-dependent carboxylase does the gamma carboxylation. Vitamin K hydroquinone is a cofactor for this and Vitamin K epoxide is a byproduct. To regenerate Vitamin K hydroquinone from the epoxide, Vitamin K epoxide reductase makes Vitamin K quinone, and Vitamin K reductase makes Vitamin K hydroquinone for reuse.

Question 26

Which LDL apoprotein binds to LDL-R?

Answer 26

B100

Question 27

In what way does the mRNA for ApoB48 differ from that for ApoB100?

Answer 27

It is edited, resulting in a premature stop codon.

Question 28

Which Apoprotein is recognized by LRP (remnant receptor)?

Answer 28

Apo-E