Lipid Synthesis and Storage Flashcards
How the omega-3 fatty acids (linolenic, ex) protect against cardiovascular disease?
- Replacing some arachidonic acid (omega-6) in platelet membranes ▶️ ⬇️ tromboxane ▶️ ⬇️ platelets aggregation
- Related ⬇️ TG
- omega-3 (-) cyclooxygenase
What other source of NADPH can we find besides HMP shunt can we find in lipogenic pathway?
- (cytoplasm, hepatocyte) OAA ▶️ malate (to return to mitochondria) ▶️ pyruvate by malic enzyme (NADP+ ▶️ NADPH)
What is the only fatty acid that human can synthesized de novo? Can we produce unsaturated?
- Palmitate (16 C)
- elongated and desaturated using SER enzymes
- cytochrome b5 desaturated but can’t do it beyond C9
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)?
- 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
What are the two sources of glycerol 3-P to TG synthesis and which of them is exclusively hepatic?
- 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)
What enzyme make the ester bond between FA and glycerol 3-P to form TG?
.
What is the function of Apo CII, what lipoprotein have it?
- activates lipoprotein lipase
- chylomicron, VLDL
True or false:
The dietary cholesterol is delivered directly by remnant chylomicron to the extra hepatic tissues with any remaining TG
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.
Where the Apo E and Apo CII come from to assemble into VLDL and chylomicron?
HDL
What is the function of LCAT?, what activates it?
- 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
What facilitates the transfer of cholesterol esters from HDL to IDL and form LDL?
Cholesterol ester transfer protein (CETP)
Where are the scavenger receptors (SR-B1) and their function?
- hepatocytes and steroidogenic tissues (ovaries, testes, adrenal gland)
- Pick up the cholesterol contained in HDL (taken in the periphery)
What event lead to the formation of the foam cell in a damaged endothelium?
phagocytosis by Macrophages of oxidized/damaged LDL
What causes the oxidation of the LDL in endothelial cell injury?
Local inflammation ▶️ recruit monocytes and macrophages ▶️ ⬆️ ROS ▶️ oxidized the LDL
In a liver failure context which apoprotein would be less affected?
Apo B48 - is synthesized in the intestine to produce and assemble chylomicrons
What sources use the adipose tissue to get fatty acids?
- chylomicrons from diet
- VLDL from liver
Effect of insulin in HMG CoA reductase
- activate it (dephosphorylate)
- induce gene expression
How cholesterol regulates its level in hepatocytes?
(De novo synthesis from Glc, taken from blood) ⬆️ cholesterol ▶️ (-) LDL-receptor expression, HMG CoA reductase, (+) ACAT
What is the function of ACAT?
Make cholesterol ester INSIDE the hepatocyte to storage ▶️ bile acids
What receptor use the macrophage to phagocytes oxidized/damaged LDL?
Scavenger SR-A receptor
Symptoms of type IIa hypercholesterolemia and what is the deficiency
- “triple X Fat and corneal”
Xanthomas Achilles tendon, elbows (subcutaneous tuberous), Xanthelasma, corneal arcus - LDL receptor deficiency
Causes of less severe hypertriglyceridemia
Diabetes (type V), alcohol, glucose 6-phosphatase deficiency
How trans configuration in double bonds and saturated FA rise cardiovascular risk?
- more rigidity of cell membrane ▶️ less space to take cholesterol ▶️ need ⬆️⬆️ LDL
How diabetes contribute con hyperlipidemia?
- ⬇️ insulin (adipose tissue) ▶️ NO induce LPL ▶️ ⬇️ LPL ▶️ ⬆️ TG
