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Date: 23-9-2021
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Very-low-density lipoprotein metabolism
VLDL is produced in the liver (Fig. 1). They are composed predominantly of endogenous TAG (~60%), and their function is to carry this lipid from the liver (site of synthesis) to the peripheral tissues. There, the TAG is degraded by LPL, as discussed for chylomicrons. [Note: Nonalcoholic fatty liver (hepatic steatosis) occurs in conditions in which there is an imbalance between hepatic TAG synthesis and the secretion of VLDL. Such conditions include obesity and type 2 diabetes mellitus .
Figure 1: Metabolism of very-low-density lipoprotein (VLDL) and low density lipoprotein (LDL) particles. Apo B-100, C-II, and E are apolipoproteins found as components of plasma lipoprotein particles. The particles are not drawn to scale. [Note: IDL can also be taken up by liver.] TAG = triacylglycerol; HDL and IDL = high- and intermediate-density lipoproteins; C = cholesterol; CE = cholesteryl ester.
1. Release from the liver: VLDL are secreted directly into the blood by the liver as nascent particles containing apo B-100. They must obtain apo CII and apo E from circulating HDL (see Fig. 1). As with chylomicrons, apo C-II is required for activation of LPL. [Note: Abetalipoproteinemia is a rare hypolipoproteinemia caused by a defect in MTP, leading to an inability to load apo B with lipid. Consequently, few VLDL or chylomicrons are formed, and TAG accumulates in the liver and intestine. Absorption of fat-soluble vitamins is decreased. LDL are low.]
2. Modification in the circulation: As VLDL pass through the circulation, TAG is degraded by LPL, causing the VLDL to decrease in size and become denser. Surface components, including the C and E apolipoproteins, are returned to HDL, but the particles retain apo B-100.
Additionally, some TAG are transferred from VLDL to HDL in an exchange reaction that concomitantly transfers cholesteryl esters from HDL to VLDL. This exchange is accomplished by cholesteryl ester transfer protein (CETP), as shown in Figure 2.
Figure 2: Transfer of cholesteryl ester (CE) from HDL to VLDL in exchange for triacylglycerol (TAG).
3. Conversion to low-density lipoproteins: With these modifications, the
VLDL is converted in the plasma to LDL. Intermediate-density lipoproteins (IDL) of varying sizes are formed during this transition. IDL can also be taken up by liver cells through receptor-mediated endocytosis that uses apo E as the ligand. Apo E is normally present in three isoforms, E-2 (the least common), E-3 (the most common), and E-4. Apo E-2 binds poorly to receptors, and patients who are homozygotic for apo E-2 are deficient in the clearance of IDL and chylomicron remnants.
These individuals have familial type III hyperlipoproteinemia (familial dysbetalipoproteinemia or broad beta disease), with hypercholesterolemia and premature atherosclerosis. [Note: The apo E-4 isoform confers increased susceptibility to an earlier age of onset of the late-onset form of Alzheimer disease. The effect is dose dependent, with homozygotes being at greatest risk. Estimates of the risk vary.]
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"عادة ليلية" قد تكون المفتاح للوقاية من الخرف
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ممتص الصدمات: طريقة عمله وأهميته وأبرز علامات تلفه
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الأمين العام للعتبة العسكرية المقدسة يستقبل شيوخ ووجهاء عشيرة البو بدري في مدينة سامراء
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