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Roles of FOX and ROR-α Genes for Sestrin-Leu-1 Synthesis and for Regulating Cholesterol which is Estrogen and Androgen's Primary Substrate

Sestrins are integrated as overlapped genes for adaptive responses against a variety of cellular inflammation and stresses procedures, including DNA damage, oxidative stress, hypoxia, and cells repairs metabolism. Sestrin is activated by forkhead (FOX) activator factor, where the Forkhead transcription factors are classified based on a conserved winged helix/forkhead DNA-binding domain consisting of three α-helices, three β-sheets, and two loops forming wings. The presence of Leu amino acids in forkhead genes and in sestrin molecules is so necessary for increasing FOX activities and for sestrin-Leu 1 molecules synthesis, where presence of hydrophobic amino acids particularly Tyr and Phe can enhance the activity of Leucine amino acids functions in sestrin-Leu 1 (sesn1) gene molecules. Sestrins molecular structure revealed three overlapped genes having functional active sites • _mTOR gene regulation activities, • _ROS gene suppression activities, • _and leucine binding active sites gene molecules, where, Sestrin-Leu 1 (sesn-1) which are originally activated by FOX forkhead transcription factors (FOXO1) which are a strong key as a regulator for hepatic glucose and for lipid regulations (their calculated activity depend on their kinetic energy in sesns1 molecules which evaluated by the percentage of Leucine amino acids in its sestrin-1 gene molecule ), where reductions in Sestrins_Leu 1 (sesn-1) activities will reflect reductions in FOX box activities, will reflect the decreasing in pyrimidine synthesis by mitochondrial enzymes, and will reflect decreasing in the purification of pro-mTOR protein by the effects of mitochondrial enzymes, thus reduction in Leu, Phe, Tyr hydrophopic amino acids will reflect the decreasing in liver activities, in brain activities, and in heart activity, due to decreasing in pyrimidine synthesis from high purines and from high branched fatty acids, that can lead to accumulation of branched fatty acids and high glucose (purines) molecules in interstitium fluid, that can lead to diabetes with blockage in blood capillaries,, Arteriosclerosis,cancer and can Leads to cardiovascular disease. The reduction in mitochondrial membranes L-OPA1 gene activities will lead to reduction in pyrimidine synthesis, with deficiency in TXA2 and TNF-a production, and lead to reduction in promTOR purification during FOX forkhead binding mechanism to pro-mTOR protein, and will reflect reductions in sestrin-Leu-1 genes synthesis, that lead to accumulation of high purines and high branched fatty acid in plasma and in capillaries lead to diabetes, Arteriosclerosis, cancer, and cardiovascular diseases.