Lysine and Tryptophan have the Protection Basis against Lysosomal Dysfunction and both PKU and CVD including Mitochondrial Disorder Mediated by Activating Lysosomes and OPA1
Authors:   Biomedical Molecular, Immunology and Cardiology Studies, Toronto Canada and Cairo, Egypt, M El Tantawi Ashraf 
Published: October 2024

The phenylketonuria “PKU” due to sever decreasing in lysine “AAG” and in Lys/ phosphorylation (which necessary for lysosomal digestive function), and associated with sever decreasing in Trp “TGG”, followed by mitochondrial dysfunction and lysosomal dysfunction, that followed by sever decreasing in phe /hydroxylase and in Tyr/ hydroxylase, and followed by decreasing in lysine acylation and in SFACs productiin which followed by decreasing in RA productive pathway and associated with increasing in both of TNFa and cholesterol accumulation which activate increasing in in both of TNFa and NLRP3 pathogenic pathway which reflect decreasing in estrogen synthesis and in dopamine production, that followed by increasing in the risk of ischemic damage pulmonary disease and diabetes. And we can conclude that both of Lys “AAG” and Trp “TGG” are so necessary for activating mitochondrial oxidative functions and necessary for promoting transport system where Mitochondria is so necessary to activate antioxidant function and promoting all of Phe hydroxylase, Tyr hydroxylase, and Lys acylation production which necessary for dopamine and RA synthesis respectively, where the PKU characterized by sever decreasing in antioxidant function, and sever decreasing in both Phe/ hydroxylase & Trp/ hydroxylase production, followed by decreasing in dopamine production and decreasing in retinoic acid production (which due to the reduction in SFACs synthesis). And I concluded that PKU characterized by sever decreasing in Phe /hydroxylase and Tyr /hydroxylase, followed by reduction in dopamine production, and reduction in alpha amylase, that associated with increasing in TNFa and in NLRP3 pathogenic pathway, and associated with increasing in the pulmonary disease and CVD risk. Retionic acid “RA” is regulated by lysine acylation and is regulated by lysine acylation mediated by short fatty acid synthesis, which regulate aminoacyl-tRNAs production regulated by mitochondrial enzymes and regulate mRNA production by E coli (regulated by phenylalanine) that necessary to run antioxidant functions and cellular biosynthesis. The antihypertensive pathway mechanism is: the Lysine →activate ATPase and both lysosomes and Mitochondrial oxidative functions which activate lysine acylation →activate short fatty acid synthesis →stimulate retinoic acid “RA” synthesis - →where both Lys and Trp activate GTPase which promote mitochondria repair and oxidative functions, which activate, Phe/ hydroxylase, and activate Tyr/ hydroxylase which activate dopamine, followed by activating NR4As pathway which responsible for activating GC-beta and both of Oxytocin and Nrf2, followed by Ang2-AT2 and VEGF-A productive functions and heme oxygenase production (notice dopamine regulate heme oxygenase mediated by dopamine beta-hydroxylase which regulated by Mitochondrial oxidative functions) followed by activating anti-inflammatory growth and processes. Lysine Methylation has important role to enhance and adopt hypertension through activating RA and pervious Antihypertensive pathway mediated by Phe/hydroxylase synthesis and Tyr /hydroxylase production followed by activating both of dopamine and NR4As pathway. Where dopamine synthesischaracterized by activating Antioxidant functions that prevent cholesterol accumulation, and in turn increase the estrogen production (which it’s synthesis reflect potential protection from pulmonary disease), and activate the NR4As pathway which regulate all of Oxytocin, Nrf2 production, followed by Ang2-AT2 and VEGF-A production, which followed by activating heme oxygenase and anti-inflammatory growth and processes that prevent LV-hypertrophy, and prevent coronary calcification. Also, the increasing in Lys AAA with decreasing in both of Lys AAG and decreasing Trp TGG will cause decreasing in lysosome proper function, and Pero cause Decreasing in GTPase and decreasing in the Mitochondrial oxidative functions, that will cause decreasing in Phe hydroxylase and in Tyr hydroxylase followed by decreasing in lysine acylation, and associated with increasing in cholesterol accumulation, and also associated with decreasing in both of IL17 production and estrogen functional pathway, that will increase the risk of T2D, pulmonary disease, and increase the risk of PKU and CVD. Both Lys and Trp are necessary to activate transport across cells membranes, that activate antibacterial function and anti-atherosclerosis, mediated by activating lysosomes and OPA1 oxidative functions, where OPA1 functions activated by GTPase productive functions which play important role in activating transport system pathways within and between cells. Lysine acylation is playing important role in activating SFACs production and RA synthesis which protect from pulmonary disease and from ischemic damage. Both Lys and Trp are having the Potency to activate lysosomes and Mitochondrial oxidative functions which activate lipid and protein digestion and enhance Phe /hydroxylase and Tyr / hydroxylase, followed by activating lysine acylation which activate SFACs production and promote the RA synthesis and enhance antioxidant functions and anticoagulant functions, followed by dopamine synthesis and protection against ischemic damage and against both of diabetes, pulmonary disease, CVD , and PKU.