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
What are the uses of the farnesyl PPi?
- synthesis of CoQ ▶️ ETC
- synthesis of dolicol PPi ▶️ N-linked glycosilation in ER
- Prenylation of proteins
What inhibit and how does it the statins drugs?
Competitive inhibitor of HGM CoA reductase
Side effects of statin drugs and why do the occur?
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
In children what use of the cholesterol synthesis is very important as a major arrow?
cell membranes is a major arrow in children because growing
