In tissues, a tight balance must be maintained between those factors which increase cholesterol levels and those which decrease them, thus keeping intracellular concentrations constant (Figure1). An increase in cell cholesterol may be caused by: (1) Uptake of cholesterol-containing lipoproteins by receptors, for example, the LDL receptor or scavenger receptors such as CD36. (2) Uptake of free cholesterol from cholesterol-rich lipoproteins to the cell membrane. (3) Cholesterol synthesis. (4) Hydrolysis of cholesteryl esters by the enzyme cholesteryl ester hydrolase. A decrease may be due to: (1) Efflux of cholesterol from the membrane to HDL via the ABCA1, ABCG1, or SR-B1. (2) Esterification of cholesterol by ACAT (acyl-CoA: cholesterol acyl transferase). (3) Utilization of cholesterol for synthesis of other steroids, such as hormones, in steroidogenic tissues, or bile acids in the liver.

Fig1. Factors affecting cholesterol balance at the cellular level. Reverse cholesterol transport may be mediated via the ABCA1 transporter protein (with preβ-HDL as the exogenous acceptor) or the SR-B1 or ABCG1 (with HDL3 as the exogenous acceptor). Stimulatory ( ⊕) or inhibitory (⊖) effects are shown as dotted green or red arrows, respectively. (ACAT, acyl-CoA:cholesterol acyltransferase; A-I, apolipoprotein A-I; C, cholesterol; CE, cholesteryl ester; LCAT, lecithin:cholesterol acyltransferase; LDL, low-density lipoprotein; PL, phospholipid; VLDL, very-low-density lipoprotein.) LDL and HDL are not shown to scale.

The LDL Receptor Plays an Important Role in the Maintenance of Intracellular Cholesterol Balance

LDL (apo B-100, E) receptors occur on the cell surface in pits that are coated on the cytosolic side of the cell membrane with a protein called clathrin. The glycoprotein receptor spans the membrane, the B-100 binding region being at the exposed amino terminal end. After binding, LDL is taken up intact by endocytosis. The apoprotein and cholesteryl ester are then hydrolyzed in the lysosomes, and cholesterol is translocated into the cell. The receptors are recycled to the cell surface. This influx of cholesterol inhibits the transcription of the genes encoding HMG-CoA synthase, HMG-CoA reductase, and other enzymes involved in cholesterol synthesis, as well as the LDL receptor itself, via the SREBP pathway, and thus coordinately suppresses cholesterol synthesis and uptake. ACAT activity is also stimulated, promoting cholesterol esterification. In addition, recent research has shown that the protein proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates the recycling of the receptor to the cell surface by targeting it for degradation. By these mechanisms, LDL receptor activity on the cell surface is regulated by the cholesterol requirement for membranes, steroid hormones, or bile acid synthesis, and the free cholesterol content of the cell is kept within relatively narrow limits (see Figure 1).

اخر الاخبار

اخبار العتبة العباسية المقدسة

شعبة متابعة الأداء تنظم محاضرة تربوية لمتطوعات مجمع العلقمي استعدادًا لزيارة الأربعين

شعبة الحرم الشريف تكثف استعداداتها لتقديم خدمات متنوعة لزائري الأربعين

قسم الشؤون الفكرية يفتتح محطتين ثقافيتين في ذي قار لخدمة زائري الأربعين

العتبة العباسية المقدسة تعقد ملتقى خاصًا لمنتسبيها العاملين في مراكز إرشاد التائهين خلال زيارة الأربعين

المزيد

الآخبار الصحية

علامات فارقة بين النوبة أو السكتة القلبية.. ماهي؟

الفلفل الأحمر.. سعرات حرارية منخفضة وفوائد صحية عديدة

8 أعراض إذا شعرت بها.. اذهب للطوارئ فورا !

تعرف على أكثر 8 أماكن اتساخا في المنزل

المزيد

الآخبار التكنلوجية

إنتاج الهيدروجين الأخضر في البحر.. هذه أحدث الدراسات

"ناسا" تخطط لبناء مفاعل نووي على سطح القمر !

ابتكار ومواهب وأموال.. مارك زوكربيرغ يعلن الحرب على أبل

عودة التعاون الفضائي بين روسيا وأميركا.. وبحث ملفات "هامة"

المزيد

مواضيع ذات صلة

Cholesterol Synthesis is Controlled by Regulation of HMG-CoA Reductase

Cholesterol is Biosynthesized From Acetyl-CoA

Brown Adipose Tissue Promotes Thermogenesis

Hormones Regulate Fat Mobilization

Adipose Tissue is The Main Store of Triacylglycerol in The Body

Classification of Proteins

Precipitation Reactions of Proteins

Study of Protein Structure

Imbalance in the Rate of Triacylglycerol Formation & Export Causes Fatty Liver

The Liver Plays A Central Role in Lipid Transport & Metabolism

HDL Takes Part in Both Lipoprotein Triacylglycerol & Cholesterol Metabolism

Tertiary Structure of Proteins