Cholesterol synthesis is tightly controlled by regulation at the HMG-CoA reductase step. The activity of the enzyme is inhibited by mevalonate, the immediate product of the reaction, and by cholesterol, the main product of the pathway. Thus, increased intake of cholesterol from the diet leads to a decrease in de novo synthesis, especially in the liver.

Regulatory mechanisms include both modulation of the syn thesis of enzyme protein and posttranslational modification. Cholesterol and metabolites repress transcription of HMG CoA reductase mRNA via inhibition of a sterol regulatory element-binding protein (SREBP) transcription factor. SREBPs are a family of proteins that regulate the transcription of a range of genes involved in the cellular uptake and metabolism of cholesterol and other lipids. SREBP activation is inhibited by insulin-induced gene (Insig), a protein whose expression, as its name indicates, is induced by insulin and is present in the endoplasmic reticulum. Insig also promotes degradation of HMG-CoA reductase. A diurnal variation occurs both in cholesterol synthesis and reductase activity. Short term changes in enzyme activity, however, are brought about by posttranslational modification (Figure 1). Insulin or thyroid hormone increases HMG-CoA reductase activity, whereas glucagon or glucocorticoids decrease it. Activity is reversibly modified by phosphorylation–dephosphorylation mechanisms, some of which may be cAMP-dependent and therefore immediately responsive to glucagon. AMP-activated protein kinase (AMPK) (formerly called HM-CoA reductase kinase) phosphorylates and inactivates HMG-CoA reductase. AMPK is activated via phosphorylation by AMPK kinase (AMPKK)and by allosteric modification by AMP.

Fig1. Possible posttranslational mechanisms in the regulation of cholesterol synthesis by HMG-CoA reductase. Insulin has a dominant role compared with glucagon. Stimulatory (⊕ ) or inhibitory ( ⊖) effects are shown as dotted green or red arrows, respectively. (AMPK, AMP-activated protein kinase; AMPKK, AMP-activated protein kinase kinase.).

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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

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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"

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مواضيع ذات صلة

The Cholesterol Balance in Tissues is Tightly Regulated

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