Lipid Synthesis and Storage

Question 1

How the omega-3 fatty acids (linolenic, ex) protect against cardiovascular disease?

Answer 1

• Replacing some arachidonic acid (omega-6) in platelet membranes ▶️ ⬇️ tromboxane ▶️ ⬇️ platelets aggregation
• Related ⬇️ TG
• omega-3 (-) cyclooxygenase

Question 2

What other source of NADPH can we find besides HMP shunt can we find in lipogenic pathway?

Answer 2

• (cytoplasm, hepatocyte) OAA ▶️ malate (to return to mitochondria) ▶️ pyruvate by malic enzyme (NADP+ ▶️ NADPH)

Question 3

What is the only fatty acid that human can synthesized de novo? Can we produce unsaturated?

Answer 3

• Palmitate (16 C)
• elongated and desaturated using SER enzymes
• cytochrome b5 desaturated but can’t do it beyond C9

Question 4

How indirectly do the insulin and a high-energy state promote citrate mobilization from mitochondria (Krebs cycle) to cytoplasm (carry acetyl CoA to FA synthesis)?

Answer 4

• high energy state ▶️ ⬆️ ATP, ⬆️ NADH (-) isocitrate DH (Krebs cycle) ▶️ ⬆️⬆️ isocitrate ▶️ ⬆️⬆️ citrate ▶️ cytoplasm
• insulin ▶️ generating more acetyl CoA activating and induced glycolytic enzymes (glucokinase, PFK2, PDH) ▶️ acetyl CoA + OAA ➡️ citrate

Question 5

What are the two sources of glycerol 3-P to TG synthesis and which of them is exclusively hepatic?

Answer 5

• DHAP from glycolysis (liver and adipose)
• glycerol kinase (only in liver) ▶️ phosphorylate free glycerol released by VLDL metabolism when delivered FA to adipose tissue (insulin)

*phosphorylate to trap glycerol inside hepatocyte in fasting released by lipolysis from adipose to make gluconeo (glucagon)

Question 6

What enzyme make the ester bond between FA and glycerol 3-P to form TG?

Answer 6

.

Question 7

What is the function of Apo CII, what lipoprotein have it?

Answer 7

• activates lipoprotein lipase

- chylomicron, VLDL

Question 8

True or false:

The dietary cholesterol is delivered directly by remnant chylomicron to the extra hepatic tissues with any remaining TG

Answer 8

False:
The dietary cholesterol and any remaining TG in the chylomicron remnant is picked up by hepatocytes through the Apo E receptor, not deliver directly at other tissues.

Question 9

Where the Apo E and Apo CII come from to assemble into VLDL and chylomicron?

Answer 9

HDL

Question 10

What is the function of LCAT?, what activates it?

Answer 10

• Add a fatty acid to cholesterol ▶️ cholesterol esters
  Allowing HDL to transport cholesterol from the periphery to the liver
• activated by Apo A-1 on HDL

Question 11

What facilitates the transfer of cholesterol esters from HDL to IDL and form LDL?

Answer 11

Cholesterol ester transfer protein (CETP)

Question 12

Where are the scavenger receptors (SR-B1) and their function?

Answer 12

• hepatocytes and steroidogenic tissues (ovaries, testes, adrenal gland)
• Pick up the cholesterol contained in HDL (taken in the periphery)

Question 13

What event lead to the formation of the foam cell in a damaged endothelium?

Answer 13

phagocytosis by Macrophages of oxidized/damaged LDL

Question 14

What causes the oxidation of the LDL in endothelial cell injury?

Answer 14

Local inflammation ▶️ recruit monocytes and macrophages ▶️ ⬆️ ROS ▶️ oxidized the LDL

Question 15

In a liver failure context which apoprotein would be less affected?

Answer 15

Apo B48 - is synthesized in the intestine to produce and assemble chylomicrons

Question 16

What sources use the adipose tissue to get fatty acids?

Answer 16

• chylomicrons from diet

- VLDL from liver

Question 17

Effect of insulin in HMG CoA reductase

Answer 17

• activate it (dephosphorylate)

- induce gene expression

Question 18

How cholesterol regulates its level in hepatocytes?

Answer 18

(De novo synthesis from Glc, taken from blood) ⬆️ cholesterol ▶️ (-) LDL-receptor expression, HMG CoA reductase, (+) ACAT

Question 19

What is the function of ACAT?

Answer 19

Make cholesterol ester INSIDE the hepatocyte to storage ▶️ bile acids

Question 20

What receptor use the macrophage to phagocytes oxidized/damaged LDL?

Answer 20

Scavenger SR-A receptor

Question 21

Symptoms of type IIa hypercholesterolemia and what is the deficiency

Answer 21

• “triple X Fat and corneal”
  Xanthomas Achilles tendon, elbows (subcutaneous tuberous), Xanthelasma, corneal arcus
• LDL receptor deficiency

Question 22

Causes of less severe hypertriglyceridemia

Answer 22

Diabetes (type V), alcohol, glucose 6-phosphatase deficiency

Question 23

How trans configuration in double bonds and saturated FA rise cardiovascular risk?

Answer 23

• more rigidity of cell membrane ▶️ less space to take cholesterol ▶️ need ⬆️⬆️ LDL

Question 23

How diabetes contribute con hyperlipidemia?

Answer 23

• ⬇️ insulin (adipose tissue) ▶️ NO induce LPL ▶️ ⬇️ LPL ▶️ ⬆️ TG

Question 25

What are the uses of the farnesyl PPi?

Answer 25

• synthesis of CoQ ▶️ ETC
• synthesis of dolicol PPi ▶️ N-linked glycosilation in ER
• Prenylation of proteins

Question 26

What inhibit and how does it the statins drugs?

Answer 26

Competitive inhibitor of HGM CoA reductase

Question 27

Side effects of statin drugs and why do the occur?

Answer 27

Hepathopathy and myopathy

• ⬇️ synthesis CoQ ▶️ ⬇️ function ETC ▶️ low ATP production for muscle to contraction
• muscle soreness, pain, weakness with exercise
• myoglobinuria (red-brown urine) ▶️ spillage myoglobin from damaged muscle cells

Question 28

In children what use of the cholesterol synthesis is very important as a major arrow?

Answer 28

cell membranes is a major arrow in children because growing