Lipid Metabolism: Cholesterol/Eicosanoids

Question 1

What structures can be made from cholesterol?

Answer 1

• Cell membrane
• Regulators of skin differentiation (Cholesterol 3-O-Sulfate)
• Bile acid
• Vitamin D3
• Steroids precursor

Question 2

What cellular functions are cholesterol important for?

Answer 2

• Intracellular transport
• Cell signaling and Nerve conduction
• Structure and functions of caveolae and clathrin coated pits w/ endocytosis

Question 3

What is the desirable level of cholesterol to be low risk HD?

Answer 3

<200Mg/dL or <5.2 mM/L

Question 4

Describe the general synthesis of mevalonate?

Answer 4

Three molecule Acetyl CoA Combine to form HMG CoA and then become reduced to form Mevalonate

Question 5

What is HMG reductase, and what is it’s clinical significance?

Answer 5

• Enzyme which reduces HMG CoA to Mevalonate

- Statins block HMG Reductase

Question 6

What important products can be made from mevalonate?

Answer 6

• Isoprenoids

- Cholesterol

Question 7

How many steps are required for cholesterol synthesis? Where is it made?

Answer 7

• 37 Steps

- Mainly in liver; sometimes in intestine, reproductive tissue, and adrenal glands

Question 8

What are the biochemical controls cholesterol synthesis when levels are high?

Answer 8

• High cholesterol inhibits HMG-CoA reductase
• High Cholesterol Activates AMP Activates kinase which I Activates HMG CoA
• High Cholesterol leads to proteosome degradation f HMG-CoA reductase
• Hormonal regulation via insulin activating protein phosphatase —> inactivation of HMG- CoA reductase

Question 9

What are the genetic control for cholesterol synthesis when levels are low?

Answer 9

• SREBP bonds SRE of HMG-CoA Reductase gene and LDL gene to stimulate transcription

Question 10

What are the genetic control fo cholesterol synthesis at high levels?

Answer 10

• In high levels, SREBP is bound to SCAP and INSIG-1 not allowing transcription

Question 11

What are side effects of statins?

Answer 11

• Muscle weakness and pain
• Occasionally: myopathy
• Peripheral neuropathy
• Reduced cognition

Question 12

What are possible replacements for statins?

Answer 12

• Co Q10
• Ubiquinone - Mt can be damaged if not enough
• Heme A - Prosthetc group for cytochrome C oxidase
• Squalene synthase inhibitors
• Zaragozic acid

Question 13

What is Smith-Leslie Optiz Syndrome?

Answer 13

• Deficiency in DHCR7, an enzyme which converts 7-DHC to cholesterol
• 15-27% reduced levels
• Malformation and behavioral problems

Question 14

What is Arcus Senilis?

Answer 14

• Results Form Cholesterol deposits in cornea

- indicates hypercholesterolemia

Question 15

What is xanthelasma?

Answer 15

Cholesterol deposit underneath the skin

Question 16

What are the most important chemicals in biles?

Answer 16

• Phosphatadylcholine

- Bile salts

Question 17

What stimulates contraction of the gallbladder and release of bile?

Answer 17

CCK

Question 18

What are the end chain compounds of Bile salts?

Answer 18

Either glycine or Taurine

Question 19

How is bile conserved?

Answer 19

• Bile acids are transported back from intestinal epithelium through portal vein to liver
• Albumin in blood ties up bile acids and is picked up by liver

Question 20

What is cholelithiasis?

Answer 20

• Less phospholipids and bile acids stored in gall bladder

- More cholesterol in bile causes precipitation of gallstones

Question 21

What biochemical function is Dolichol used in?

Answer 21

Synthesis of N-linked glycoproteins

Question 22

How many steps are involved in de novo synthesis of cholesterol?

Answer 22

37 Steps

Question 23

How are prostaglandins synthesized de novo?

Answer 23

Free Arachidonic acid (released by Phospholipasee A-2) —> PGG2 (COX) —> PGH2 (Peroxidase)

Question 24

What is the role of Cortisol signaled lipocortin?

Answer 24

Inhibits PLA-2

Question 25

How does aspirin regulate synthesis of prostaglandins?

Answer 25

Inhibits COX

Question 26

What is the role of prostacyclin (PGI2)?

Answer 26

Produced by vascular endothelial cells to inhibit platelet aggregation and stimulate vasodilation and block thrombogenesis

Question 27

What is PGF(alpha2) produced in?

Answer 27

• Produced by most tissues
• In corpus lute up
• Contraction Of Smooth muscle
• Stimulates uterine contraction

Question 28

What is the role of Thromboxane (TXA2)?

Answer 28

Thomboxanes A2 is produced in activated platelets. TX2 promotes adherence and aggregation of circulating platelets and contraction of vascular smooth muscle and promotes clot formation

Question 29

Describe de novo synthesis of leukotrienes.

Answer 29

• Arachidonic acid is substate

AA —> (5-lipoxygenase) 5HPETE —> Leucotriene A4/B4/C4/D4

Question 30

Where is LTB4 produced and released?

Answer 30

• Produced by polymorphonuclear leukocytes
• Increases chemotaxis
• release of lysosomal enzymes
• Causes adhesion of WBC

Question 31

What are the effects of LTE4?

Answer 31

• Bronchocontriction
• Vasoconstriction
• Increased vascular permeability
• Contraction of smooth muscle
• Components of slow-enacting substances of anaphylaxis

Question 32

What is the effect of Zyflo?

Answer 32

Inhibition of 5-lipoxygenase

Question 33

What is the actions f Accolate (Zafirlukast)?

Answer 33

Leukotrienes receptor inhibitor