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Highlights Steroid Metabolism / Fat Transport
1. The liver senses the body's need for lipids via LDL receptors. If lipids are needed, VLDLs are packaged by the liver and released. These get degraded by lipases and other enzymes to IDLs and LDLs. LDLs are taken up by cells when needed. If the liver LDL receptor cannot detect LDLs in the blood, it continues to release more lipids in lipoprotein complexes.
2. LDL receptors are a leading cause of high blood cholesterol. Other factors to consider include dietary cholesterol, cholesterol synthesis rate, and efficiency of recycling cholesterol. Statins inhibit HMG-CoA Reductase.
3. LDLs are referred to as "bad" cholesterol, because they are associated with formation of atherosclerotic plaques.
4. HDLs are referred to as "good cholesterol", because they are associated with reducing levels of cholesterol. HDLs are reduced in smokers, but are increased in response to exercise.
5. LDLs can lead to formation of atherosclerotic plaques. These arise due to oxidative damage of unsaturated fatty acids in the LDL by reactive oxygen species. The immune system attacks these damaged LDLs.
6. Factors increasing LDLs include smoking, obesity, and saturated fat in the diet.
7. High levels of HDLs correlate with reduced incidences of atherosclerosis. Factors increasing HDLs include exercise and factors decreasing them include obesity and smoking.
8. SREBP (Steroid response element binding protein) is a protein that plays a role in controlling whether or not HMG-CoA reductase is made. When cholesterol is abundant, SREBP is found in the membrane of the endoplasmic reticulum linked to SCAP through the regulatory (REG) region of SREBP. When cholesterol is abundant, SCAP-SREBP-A is held in the endoplasmic reticulum's membrane by a protein called INSIG
9. When cholesterol levels in the cell fall, the SCAP/SREBA complex loses its connection to INSIG and moves to the Golgi Complex where serine protease cleaves SREBP-A to release SREBP-B. SREBP-B migrates in the membrane to a metalloprotease, which clips the DNA binding region to free SREBP-C from the membrane-bound portion. The SREBP-C enters the nucleus and binds to the promoter region in front of the HMG-CoA Reductase, causing HMG-CoA Reductase to be synthesized.
10. HMG-CoA reductase can be broken down when cholesterol is abundant. Another INSIG carries an enzyme to ubiquitinylate the HMG-CoA reductase. Ubiquitin is a "flag" to the cell to digest it with a protease.
11. Phosphorylation of HMG-CoA reductase is also regulated by feedback inhibition and phosphorylation. Thus, HMG-CoA reductase can be regulated in multiple ways - synthesis, degradation, phosphorylation, allosterism.
12. Cholesterol is a precursor of the bile acids. Two examples include glycocholate and taurocholate.
13. Cholesterol is a precursor of the steroid hormones - all derived from pregnenolone and include Androgens (male sex hormones), Estrogens (female sex hormones), Mineralocorticoids (regulation Na/K and blood pressure), Glucocorticoids (fat/protein degradation & swelling/inflammation), and Progestagens (maintenance of pregnancy) .
14. Conversion of androgens to estrogens requires action of the aromatase enzyme. Some tumors are stimulated by estrogens, such as estradiol. Inhibition of them by aromatase inhibitors is a strategy of some chemotherapies.
15. Vitamin D is derived from cholesterol. A reaction converting 7-dehydrocholesterol to Previtamin D3 requires ultraviolet light. Conversion of Previtamin D3 to Vitamin D3 occurs spontaneously.
Fatty Acid Oxidation
1. Breakdown of fats occurs by action of enzymes known as lipases.
2. Fatty acid oxidation and fatty acid synthesis are almost identically the chemical reverse of each other.
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