Step 1 - Biochem 5

omranalzobaidi's version from 2015-12-08 21:03

cholesterol synthesis

Question Answer
Cholesterol synthesis-Rate-limiting step is catalyzed by HMG-CoA reductase (converts HMG-CoA to mevalonate)
- 2/3 of plasma cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT)
- Statins inhibit HMG-CoA reductase
Essential fatty acidsLinoleic and linolenic acids - Arachidonic acid, if linolenic is absent - Eiconasoids are dependent on essential fatty acids.
Pancreatic lipasedegradation of dietary TG in small intestine
Lipoprotein lipase (LPL)degradation of TG circulating in chylomicrons and VLDLs
Hepatic TG lipase (HL)degradation of TG remaining in IDL.
Hormone-sensitive lipasedegradation of TG stored in adipocytes.
Lecithin-cholesterol acyl transferase (LCAT)-Catalyzes esterification of cholesterol.
-Nascent HDL becomes mature HDL
Cholesterol ester transfer protein (CETP) mediates transfer of cholesterol esters to other lipoprotein particles
Apolipoprotein A-IActivates LCAT.
Apolipoprotein B100Binds to LDL receptor, mediates VLDL secretion.
Apolipoprotein C-IICofactor for LPL.
Apolipoprotein B-48Mediates chylomicron secretion.
Apolipoprotein EMediates Extra (remnant) uptake
LipoproteinsComposed of varying proportions of cholesterol, triglycerides(TGs) and phospholipids. LDL and HDL carry most cholesterol.
Chylomicron function/route-Delivers dietary TGs to peripheral tissue.
-Delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their TAGS
- Secreted by intestinal epithelial cells.
Apolipoproteins in chylomicronB-48, A, C, E
VLDL function/routeDelivers hepatic TGs to peripheral tissue, secreted by liver
Apolipoproteins in VLDLB-100, C, E
IDL function/routeFormed in the degradation of VLDL.
Delivers cholesterol to liver, where they are degraded to LDL
Apolipoproteins in IDLB-100 and E
LDL function/route-Delivers hepatic cholesterol to peripheral tissues.
-Formed by LPL modification of VLDL in the peripheral tissue. -Taken up by target cells via receptor-mediated endocytosis.
Apolipoprotein in LDLB-100
HDL function/route-Mediates reverse cholesterol transport from periphery to liver. -Acts as a repository for apoC and apoE (which are needed for chylomicron and VLDL metabolism).
- Secreted from both liver and intestine
(Looks lik e liver prefers CE over CH)
Familial dyslipidemias I - hyperchylomicronemia1. Increased chylomicron
2. Elevated TG, cholesterol
3. LPL deficiency or altered apoliprotein C, causes pancreatitis, hepatosplenomegaly and eruptive/pruritic xanthomas (no increase in risk for atherosclerosis)
Familial dyslipidemias IIa - familial hypercholesterolemia1. Increased LDL
2. Elevated blood cholesterol
3. Autosomal dominant
- absent or ↓ LDL receptors.
-Causes accelerated atherosclerosis, tendon (Achilles) xanthomas and corneal arcus~
(2 tendons, 2 eyes)
Familial dyslipidemia IV - hypertriglyceridemia1. Increased VLDL
2. Elevated Triglyceride in blood
3. Hepatic overproduction of VLDL
- causes pancreatitis
Abeta-lipoproteinemia-Hereditary inability to synthesize lipoproteins due to deficiencies in apoB100 and apo b48
-autosomal recessive,
- Sx appear in the first few months of life.
-Intestinal biopsy shows accumulation within enterocytes due to inability to export absorbed lipid as chylomicrons. . Findings: failure to thrive, steatorrhea, acanthocytosis(spikey RBC), ataxia, night blindnessRx Vit E