RAC1 Rich Proline are OPA1 Flux Influencer for PLCS and IFNS Synthesis where Immune and Toxicity Due Deficiency in Synthetase and in Proline Synthesis.
Ashraf Marzouk El Tantawi *
Corresponding Author: Ashraf Marzouk El Tantawi, Department of Psychology, The Islamia University of Bahawalpur, Pakistan.
Copy Right: © 2022 Ashraf Marzouk El Tantawi, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received Date: April 07, 2022
Published Date: May 01, 2022
Rac1 is the basis for ATPase, ribosomes repairs, Gactin activities, and regulating fatty Acyl-COA productions (upon OPA1 function) which are main for epidermal growth factor "EGF" synthesis and for both PLCs and IFNs synthesis.
Rac1 basically are S6K rich Proline and hydrophobic amino acids that each amino acid especially Proline characterize Rac1 for specific functions and activity for regulating specific anti-inflammatory cycles and specific anti-inflammatory growth, that Rac1 has the roles of acting on inflammatory sources for analyzing and producing long fatty chains which will follow the OPA1 oxidative function (which activated by GTPase which promoted by Rac1 active molecules ) for producing fatty Acyl-COAs isoforms which considered as GP-GTP isoforms Gp-GTP gamma, GP-GTP beta, and GP-GTP alpha isoforms where some said that GTPase has been analyzed to give Gp isoforms but GTPase has activated OPA1 enzymes which produced Gp-GTP nuclear isoforms upon the effect on long fatty chains, that GP-GTP beta and alpha have the roles of promoting PLCs and IFNs isoforms for anti-inflammatory processes and for anti-inflammatory growth.
That The Rho family Rac1-GTPase (Gp isoforms) mediates a variety of signal transduction processes leading to activation of NADPH oxidase, actin cytoskeleton reorganization, and anti-inflammatory growth. The main active amino acids that most imp amino acid that Characterized the Rac1 function are the Proline amino acids and then hydrophobic amino acids (Tyr, Ser, Leu,), where Proline have basic oxidative roles in amino acids synthesis (regulated by aminotransferase). Also, the synthesis of proline itself is carried out from the conversion of glutamate to Proline, that the
Deficiency in synthetase and in Proline synthesis due to decreasing in oxidative phosphorylation processes (regulated by OPA1 synthetase) will lead to accumulation of glutamate in brain and in neuronal tissues which is the sign of immune toxicity and signs of neuronal toxicity.
As Proline promotes the synthesis of the amino acid by aminotransferase regulations, the presence of Proline in Rac1 will perform the same roles of amino acids synthesis for DNA synthesis by repairing the deficiency of amino acids through rebinding with nucleotides during amino acids synthesis, and for thioesterase binding to form Rac1 thioesterase which will stimulate PLCγ1 then Plcγ2 for TXA2 synthesis for platelets renewing.
KPNA2 (which has the glutamatergic effect necessary for Proline synthesis from glutamate that prevents the accumulation of glutamate and protects the availability of Proline coverage and hydrophobic acids in Rac1 molecules for running various dependent cellular activities including anti-inflammatory growth.
Vit D metabolites takes place in liver and in blood that bound to proteins then upon histone deacetylase and amino-transferase to promote Proline synthesis for active proper Rac1 synthesis.
BCL-6 is regulated by Rac1-rich Proline Signaling activities, that Rac1 regulates and controls genes transcriptions processes, and binds to protein for phosphorylation oxidative processes for activating Gp-GTP active subunits productions necessary for PLCs and IFNs productions which are necessary for anti-inflammatory cycles and for anti-inflammatory growth mediated by PLCγ2 and IFN-beta production.
The Aminotransferase enzymes activated by Proline in Rac1 are necessary for recovering the Hyperammonemia toxicity.
The activation of glutamate receptors and Rac1-GTP subunits receptors can activate and increase microtubule ddepolymerizationdue to conversion of glutamate to Proline synthesis and then due to promoting Gp GTP subunits upon activating OPA1 by GTPase molecules synthesis for acting on inflammatory long fatty chains which firstly formed due to effect of Rac1 on inflammatory sources (where Proline synthesis prevent glutamate accumulation and activate Rac1 synthesis regulated by OPA1 synthetase enzymes ).
That firstly Rac1 molecules act on inflammatory sources for producing phorbol +ROS + long fatty chains productions which upon OPA1 effects will create the fatty Acyl-COAs "G-proreins-GTP isoforms" which promote and increases neuronal growth and immune anti-inflammatory upon PLCs and IFNs productions.
So, it can be understandable that is why Rac1-rich-Proline (and Tyr, Ser, Leu) are so necessary for regulating various of cellular Biosynthesis, including anti-inflammatory growth, PLCs and IFNs synthesis, bones growth, DNA repair, binding to phosphorylation protein, TXA2 synthesis, and T-cells modulations too.
The necessity of proline synthesis (to prevent glutamate synthesis) for regulating amino acids synthesis regulated by GSA aminotransferase are so necessary to promote ALA synthesis in heme. The inhibition or Proline synthesis reflect Extracellular glutamate accumulation and inheritance in aminotransferase that will cause neurotoxicity and brain damage. Also, Inhibition in Pproline and consequently in proper Rac1 synthesis can cause hypoxia that will be main reason for decreasing the stimulation of OPA1 enzymes oxydative processes and decreasing in G-prorein-GTP-subunits synthesis.
Also, Inhibition in Sestrins (gamma, beta, and alpha) genes in invertebrates reflect the accumulation in long fatty chains and increasing in oxidative damage, and mitochondrial OPA1 dysfunction that will be the result of inhibition in G-prorein-GTP-beta and G-prorein-GTP-alpha productions that followed by inhibition in PLCγ2 and in IFN-beta productions.
Methods and Results :
Rac1 is basis for ATPase, Gactin growth and for fatty Acyl-COA productions ( upon OPA1 function) which are main for EGF synthesis and PLCs synthesis, where any deficiency in the main proper Rac1 synthesis will lead to mutated EGF synthesis that will lead to metastasis due to decreasing in the efficiency of Rac1 synthesis.
Where, the interaction between PLC-γ1 SH3 domain and Rac1 play a significant role in EGF-induced F-actin formation and cell migration.
S6K containing enough Proline and hydrophobic amino acids (Tyr, Leu Ser, Pro...) which produced from mTOR Ser Thr phosphorylation will activate JAK signaling for SH3 productions are necessary for activating Acyl-COA gamma for PLCγ1 productions where both interactions will induce both Plcγ2 and epithelial growth factor (EGF) that will have imp. Roles in G-actin filaments growth and at the same time induce electron charges and signals migration for activating the rest of anti-inflammatory cycles and anti-inflammatory growth processes.
Proline is the only amino acid that the side chain is connected to the protein backbone twice, forming a five-membered nitrogen-containing ring, that is why Proline in Rac1 gives the advantages of amino acids synthesis, DNA repair, tissue growth that are so important for proliferation.
Proline biosynthesis done through glutamate phosphorylation to γ-glutamyl phosphate by γ-glutamyl kinase, reduced to γ-glutamyl semialdehyde by γ-glutamyl phosphate reductase, cyclized spontaneously to Δ(1)-pyrroline-5-carboxylate and reduced to proline by Δ(1)-pyrroline-5-carboxylate reductase.
Where, Deficiency in Proline synthesis due to decreasing in oxidative phosphorylation process will lead to accumulation of glutamate in brain and neuronal tissues which is sign of immune toxicity.
And also, as Proline promote the amino acids synthesis through necessary aminotransferase regulations, as the presence of Proline in Rac1 will perform the same roles of amino acids synthesis for DNA synthesis by repairing the deficiency of amino acids by rebinding with nucleotides during amino acids synthesis, for thioesterase binding to form Rac1 thioesterase which will stimulate PLCγ1 then Plcγ2 for TXA2 synthesis for platelets renewing.
That, Rac1 appears for protein kinase binding for stimulating fatty Acyl-COAs synthesis upon OPA1 enzymes activities for producing gamma, beta, and alpha Acyl-COAs for IFNs and PLCs for Gactin re-activities, for bone growth, anti-inflammations, for T-cells modulations and for cells proliferation.
Also, as Rac1 has the roles of protein localization to plasma membrane and for inflammatory response (eg localization of MHCs on cells membrane for SIRPa1 and TLR4 syndrome (regulated by IFNs synthesis ) as indicating Rac1 is the main basis for the various cellular processes eg for regulating PLCs and IFNs Biosynthesis, where Rac1 has roles of for designing and creating necessary proteins according to inflammations responds necessary for anti-inflammatory growth and necessary for creating MHCs and PLCs to be located on plasma membrane for activating anti-inflammatory cellular processes and growth.
Where, Rac1 promotes intestinal epithelial restitution by increasing Ca2+ influx through interaction with phospholipase C- 1 after wounding. 
And, expression of activated versions of the Cdc42 or Rac1-GTPase restores antigen-stimulated Ca2+ mobilization necessary for degranulation in these mutant cells. 
Rac1 are a specific S6K-rich-Proline molecules that are strong regulator and activator for PLCγ1 synthesis upon Rac1-GTP-gamma synthesis for restore Ca+.
Rac1 activities start by both ATPase and GTPase productions, where GTPase necessary for activating mitochondrial OPA1 membrane for for activating OPA1 enzymes for creating designed necessary anti-inflammatory protein responds through BTK regulations and PLCγ1 synthesis will produce PLCγ2 synthesis for anti-inflammatory processes followed by PLC-alpha and IFN-alpha synthesis for anti-inflammatory growth including bone growth, epidermal growth and Ca restoration.
And, the Rac1 functions are controlling and regulate the representation of genes transcription.
That, the transcriptional repressor BCL-6 is regulated by Rac1 Signaling activities.
That Rac1 mediate repression of gene transcription.
Rac1 functions are controlling and regulate the representation of genes transcription.that has the roles of promoting amino acids synthesis upon is containing Proline which is so necessary for amino acids synthesis( regulated by aminotransferase)and has the oxidative function on inflammatory source for designing and re-creating the new designed protein chain firstly in the form of G-prorein gamma then G-prorein beta and then G-prorein alpha that are responsible for PLCs and IFNs synthesis for anti-inflammatory purposes and anti-inflammatory growth that includes B-cells maturation, T-cells modulations for anti-inflammatory responds, and includes TXA2 synthesis.
Also, Rac1 functions has a significant influence on certain brain functions like neuronal migration, synaptic plasticity, and memory formation via regulation of actin dynamics in neurons.
Rac1 functions has a significant imp roles in activating both ATPase and GTPase productions where has imp roles of acting on inflammatory sources as wounds and suppurationsand generating ROS and long fatty acids chains that consequently will influence and promote OPA1 enzymes activities for producing Acyl-COAs isoforms necessary for PLCs and IFNs synthesis for increasing anti-inflammatory processes and growth that can influence on certain brain functions like neuronal migration, synaptic plasticity, and memory formation via regulation of actin dynamics in neurons activities and growth through reactivating G-actin for neuronal migration, synaptic plasticity, and restore memories which can be run by sestrins synthesis which can be started by signals migration from stimulated Rac1 activities , that SESNs synthesis are regulated by re-activating B-cells upon PLCγ1 and IFN gamma functions for promoteing PLCγ2 synthesis (upon BTK regulations) where SESNS are molecules needed for migrating amino acids and necessary for activating brain cells functions eg Leu and Met pentapeptides necessary molecules for enkephalin tissue activities which are necessary for activating memories and restore them in various tissues cells including brain .
bone morphogenetic protein 2 (BMP-2) consecutively and interdependently activates the wingless (Wnt)–β-catenin (βC). 
The Rho family Rac1-GTPase mediates a variety of signal transduction processes leading to activation of NADPH oxidase, actin cytoskeleton reorganization, transcription activation, and stimulation of DNA synthesis. 
That as Rac1 contain active Proline which can form Rac1 GTPase upon stimulating GTPase synthesis for reactivating OPA1 enzymes activities that will include creating signals transmission necessary for stimulating OPA1 enzymes activities, as Rac1 is carrying the imp function for activating Gactin for neuronal growth and activities, and has the imp roles for controlling and adopting transcription processes that will include creating active signals for activating necessary enzymes proteins for amino acids synthesis, and for DNA synthesis commentaires eg Activating aminotransferase for amino acids synthesis and activating OPA1 enzymes for pyrimidine synthesis (upon synthetase effects) necessary for hydrophobic amino acids synthesis .
Since Proline needed for transferase enzymes for producing ornithine. Which necessary for amino acids synthesis as Rac1 regulate DNA synthesis, B-cells maturation through regulating PLCγ2 synthesis and regulate antigen synthesis.
That originally Rac1 Biosynthesis regulated firstly by S6K productions from nutrient mTOR phosphorylation (regulated by ribosomal ATPase) pathway containing enough Proline and necessary hydrophobic amino acids necessary for Rac1 active functions including reactivating OPA1 enzymes through producing GTPase enzymes, that OPA1 enzymes necessary for producing Acyl-COAs upon acting on long fatty chains (which produced from the effects of Rac1 on inflammatory sources).
Where it has been reported that Rac1-dependent Protein Kinase N-γ Promotes Phospholipase Cγ1 Activation, Ca2+ Signaling, 
Rac1-dependent Protein Kinase N-γ (G-prorein kinases) are the basis of regulations for Promoting Phospholipase Cγ1 activities (through firstly activating Acyl-COAs synthesis by OPA1 effects ) which then promote PLCγ2 and IFN beta (IFNγ2) synthesis which promote anti-inflammatory growth and create the new active anti-inflammatory subunits according to inflammatory responds.
The Rac Molecules when characterized with the availability of the active Proline which contain active oxygen linkages will have the ability to run oxidative analyzed processes to act on fatty nutrients Molecules and inflammatory molecules for producing long fatty chains, and in the main time will stimulate synthetase enzymes within OPA1 membrane for acting n inflammatory source for producing phorbol esters and long fatty chain and running the pyrimidine synthesis from purines that pyrimidine will be the mediator in the necessary Hydrophobic amino acids synthesis (which regulated by aminotransferase enzymes) especially Tyr, Ser, leu, Met and ÎLe which will activate tyrosine phosphorylation cycles and BTK which are so imp for activate PLCγ2 ( from PLCγ1) that PLCγ2 will activate B-cell maturations, anti-inflammatpry processes and anti-inflammatory growth through activating PLC-alpha by more phospholipase that will activate the functioning Ca+ to be migrated to the under configurated tissue.
As, S6K containing enough Proline and necessary hydrophobic amino acids (as Tyr, Ser, Leu..) which are the basis of Rac1 (which have roles of -4,5-bisphosphate 3-kinase activity, ATPase binding, GTPase production and binding and nucleotides binding) as indicating Rac1 have the roles of activating ATPase through ribosomes repair and promote GTPase re-production (which necessary for OPA1 repair), that Rac1 necessary for activating ATPase (whether in ribosomes or in Gactin filaments ) for acting on lipids molecules (fatty inflammatory sources) for producing long fatty acids chains which upon OPA1 enzymes effects will produce fatty Acyl-COA-gamma, beta, and alpha respectively which regulate PLCs and IFNs synthesis.
And also Rac1-rich Proline have the roles of nucleotide binding for amino acids synthesis through analyzing the complex proteins for simple forms (mediated by stimulating synthetase for pyrimidine synthesis) for amino acids synthesis through producing ornithine (upon aminotransferase effect ) necessary for hydrophobic acids synthesis , so Rac1 has the role of amino acids synthesis .
So now it can be understandable that why Rac1 rich Proline (and Tyr, Ser, Leu) are so necessary in regulating various of cellular Biosynthesis, including bones growth and immune effective growth, and T-cells modulations too.
Rac1 can modulate OPA1 repairs for nuclear Rac1 which mediated by Acyl-COAs synthesis for nuclear Rac1 GTPase synthesis that will be accumulate on nucleus for bFGF productions necessary for neuronal differentiation and growth, and neurite outgrowth which induced neuronal differentiation in PC12 cells.
Where, Rac1 translocation to the nucleus functionally correlates with bFGF-induced neurite outgrowth. 
Karyopherin alpha 2 (KPNA2) (which have the glutamatergic synapse and has histone deacetylase binding functions mediates the nuclear import of Rac1 by directly binding the NLS through active GTP-bound Rac1 nuclear compartment during Cell differentiation-related role for nuclear Rac1 . That KPNA2 (which have the glutamatergic effect necessary for Proline synthesis from glutamate that prevents the accumulation of glutamate and protect the Pproline coverage and hydrophobic acids in Rac1 for running various dependent cellular activities.
Vit D metabolites takes place in liver and in blood that bound to proteins then upon histone deacetylase and amino-transferase will promote Proline synthesis which will be directed for necessary Hydrophobic amino acids synthesis upon aminotransferase effect (and mediated by synthetase functions for pyrimidine synthesis) for proper amino acids synthesis, that previous pathway can be promoted by vitamin D which promote own vit D receptor (VDR) Upon stimulating and activating OPA1 enzymes effects for active proper Rac1 synthesis from histone deacetylation and from glutamate for controlling and regulating various transcription and cellular processes. Where VDR is a transcription factor that partners with other transcription factors such as retinoid X receptor when bound to 1,25(OH)2D regulates gene transcription either positively or negatively depending on other cofactors to which it binds or interacts. 
Notice that Rac1 has a role of biological processes of vascular endothelial growth factor receptor that indicate Rac1 has the main regulations for endothelial growth that has the main control for building main receptors for endothelial growth mediated by PLCγ2 and IFN-beta synthesis for improving anti-inflammatory cycles followed by PLC-alpha and IFN-alpha systems for anti-inflammatory growth mediated by SIRPa1 and TLR4 synthesis.
Neuronal migration and axon growth are basically promoted and regulated by availability of active Proline in Rac1 molecules which regulate signals migration and G-actin activities (upon GTPase production) in a pathway mediated by GTPase synthesis for promoting OPA1 enzymes influencer fluxes for acting on long fatty acids chains (which produced upon Rac1 effect on inflammatory sources) for fatty Acyl-COAs synthesis started by Acyl-CoA-Gamma, followed by acyl-CoA-beta then by Acyl-CoA-alpha "for PLCs and IFNs synthesis , where Rac1 rich Proline are key events for neuronal developments, and the main regulator needed for improvements in the cytoskeleton started by anti-inflammatory improvements followed by anti-inflammatory tissue growth.
That Rac1 recruits the WAVE complex to the plasma membrane to enable actin remodeling necessary for axon growth. 
The remodeling actin is proceeded upon
Rac1 functions through promoting GTPase synthesis (upon the type of received signals) that will be able to promote OPA1 repair which will promote the G-prorein GTP subunits synthesis which are so imp for PLCs and IFNs synthesis for activating G-actin re-modulations for axon growth.
Rac1 will activate several pathways necessary for remodeling neurons upon anti-inflammatory responds and growth eg promoting fatty acids chains synthesis then produce GTPase for activating OPA1 repair for activating PLCs and IFNs isoforms synthesis for beta-cells maturations, T-cells modulations and TXA2 synthesis for recovering new cells and tissues growth.
The presence of 1α,25-Dihydroxy-Vitamin D3 (1α,25(OH)2D3) in tissue (which produced upon hydroxylase effects on Vit D) will increase the OH linkage’s function that can increase the oxidative binding activity for Rac1 rich Proline synthesis through increasing the Proline synthesis that will consume glutamic and glutamate found in vivo then recreate modified active Rac1 molecules through availability of their active Proline and active hydrophobic amino acids that can increase the Rac1 oxidative function on producing long fatty chains + ROS (upon Rac1 and ATPase effects on fat and on inflammatory sources ) and then will promote GTPase for promoting OPA1 enzymes activities (OPA1 repairs) for producing fatty-Acyl-COAs isoforms (G-prorein GTP subunits) which necessary for activating both PLCs and IFNs for modulating anti-inflammatory processes and growth including B-cell maturations. Where,1α,25-Dihydroxy-Vitamin D3 (1α,25(OH)2D3 can modifies actin cytoskeleton in Ishikawa cells, a well differentiated endometrial carcinoma cells line. 
Also, Rac1 are activating the amino-transferase enzymes for amino acids and Proline synthesis necessary for creating subunits for anti-inflammatory growth and cells proliferation if likely can be potentiated by presence of vit D 3 (1α,25(OH)2D3) which formed in vivo upon hydroxylase effects on Vit D.
The main activities of Rac1 (that considered as active S6K rich Proline) is re-activating both ATPase and GTPase productions, where GTPase are necessary for OPA1 repair for their enzymes fluxes functions for Acyl-COAs isoforms productions which necessary for PLCs and IFNs synthesis which are necessary for cellular growth and anti-inflammatory growth too. That PC12 cells is potentiated by dibutyryl cyclic adenosine monophosphate (dbcAMP) which is the property for nerve growth factor "NGF" mediated by G-prorein GTP subunits productions and PLCγ1 with IFN-Gamma synthesis for nerve growth factors synthesis.
That both NGF and bFGF may share common intracellular events leading to neurite outgrowth and synergism with dbcAMP and forskolin. 
The G-prorein beta subunits is produced upon hydrolysis of Rac1-GTPase molecules by synthase oxidative effects which preceded by effect of synthetase oxidative process on Rac1-GTPase for producing G-prorein gamma "Gpγ" which promote fatty Acyl-COA beta "GpB" synthesis. Where, Gβγ in PC12 cells induced neurite outgrowth but in the absence of added NGF. That glutamate receptors in vivo which I consider it as long fatty chains as analyzed protein upon ATPase and Rac1 effects that can be remodulated by OPA1 enzymes effects for fatty Acyl-COAs which promote NGF and FGFR2 synthesis for activating Gactin and microtubule depolymerization.
Where it has been reported that Activation by Gq-coupled muscarinic receptors or glutamate receptors (mGluR1α) causes microtubule depolymerization and association of tubulin with plasma membrane proteins in living cells. 
Notice, activation of glutamate receptor by OPA1 enzymes will promote pyrimidine synthesis and Proline synthesis which promote, then will activate hydrophobic acids synthesis which will promote the proper G-prorein – GTP subunits receptors synthesis which will activate PLCγ2 and IFN-beta synthesis that will activate the increasing of microtubule de polymerization due to conversion of glutamate to Proline upon OPA1 effects and increases neuronal growth and immune anti-inflammatory growth.
Also, the active G-prorein alpha "Gα" subunit 12/13 regulates small GTPases affecting the actin and tubulin cytoskeleton. Gβγ subunits may also activate effector molecules, such as ion channels. 
Studies suggest that α and βγ subunits of G proteins (which produced upon GTPase and OPA1 activation which layer activate both PLCs and IFNs synthesis) interact with tubulin/microtubules to regulate assembly/dynamics of microtubules, providing a novel mechanism for hormone or neurotransmitter induced rapid remodeling of cytoskeleton. 
That , actually I report that Gp-α, Gp-β, and γ subunits of oxidized G-proteins by GTPase, synthase & by phospholipase are originally formed due to the proper Molecular composition and activity of Rac1 that regulate various cellular oxidative activities including G-prorein GTP subunits synthesis which necessary for PLCs and IFNs productions and then for MHC-class-I and MHC class 2 then SIRPα1 and TLR4 synthesis for anti-inflammatory processes and growth and , that those Gp-Beta and Gp-alpha promote PLCγ1, PLCγ2, PLC-alpha, and IFN-beta and alpha for anti-inflammatory growth and providing a novel mechanism for neurotransmitter induced rapid remodeling of cytoskeleton.
My notes is,
Active Rac1 is the S6K rich Proline and rich necessary Hydrophobic amino acids as Ser, Tyr, and Leu, that when Rac1 activated will have the functions of producing ATPase that can act on inflammatory source producing long fatty acids chains then at the main time will activate GTPase synthesis which activate OPA1 inner membrane repair for producing their enzymes started by synthetase which has necessary roles for pyrimidine synthesis necessary for amino acids synthesis (regulated by Proline and amino transferase) and that enzyme necessary for acting on fatty acids chains for producing fatty Acyl-COA gamma mediated by dissociation of GTPase to bind with the Acyl-COA- gamma subunits that will be considered as G-prorein GTP-gamma (Gpγ), and then will follow the synthase effect on Gpγ to produce G-prorein-GTP -beta "GpB" which upon phospholipase effects will produce Gp-GTP-alpha which responsible for the proliferation and anti-inflammatory processes and growth, where that Previous pathway is done by activating phosphodiesterases necessary for Acyl-COAs isoforms synthesis where each isoform contain analyzed cleaved Gp-GTP subunits from the analyzed cleaved GTPase, and also that attenuate Rac1 pathway which is a necessary mechanism done through activating active Rac1 rich Proline and hydrophobic acids, that the first effects of Rac1 on inflammatory source is for long fatty chains productions then for GTPase productions for stimulating the activated OPA1 (upon GTPase effect ) to act on previous long fatty chains for producing the three G-prorein-GTP subunits isoforms that first Gp-GTP-gamma subunit has own functions for activating the GP-GTP-Beta subunits which is necessary for activating Plcγ2 and IFN-beta synthesis for strengthen anti-inflammatory processes which will activate the third G-prorein-GTP-alpha subunits which responsible for anti-inflammatory growth activities.
As the Gp-GTP-Beta and Gp-GTP -alpha formed as will activate Polymerization of microtubules and regulate assembly/dynamics of microtubules, providing a novel mechanism for neurotransmitter induced rapid remodeling of cytoskeleton growth through activating PLCγ2 & IFN-beta Synthesis for anti-inflammatory processes then for anti-inflammatory growth including the TXA2 synthesis (which regulated by PLCγ2 and BTK activations ) .
Where, the three G-prorein-GTP subunits isoforms are having their own active receptors which formed upon OPA1 phosphorylations processes which produce Gp-GTP- γ, Gp-GTP-B, and Gp-GTP-alpha upon synthetase, followed by synthase then followed by phospholipase respectively.
Notice that, activating the Gp-GTP-γ interactions with tubulin down-regulates this signaling pathway due to activating synthetase pathway for running pyrimidine synthesis followed by amino acids synthesis regulated by Proline and aminotransferase enzymes. Purified Gβγ, alone or with phosphatidylinositol 4,5-bisphosphate (PIP2), inhibited carbachol-evoked membrane recruitment of tubulin and Gαq transactivation by tubulin (which is the 1st step regulated by synthetase for Gpγ synthesis), but Polymerization of microtubules elicited by Gβγ (which is GpB) that can reduce the inhibition of PLCβ1 (through activating the PLCγ2 synthesis) observed at high tubulin concentration. That study revealed the spatiotemporal pattern of Gβγ/tubulin interaction during carbachol stimulation of neuroblastoma SK-N-SH cells. [18,19]
As I mentioned previously that as Rac1 is a S6K-rich Proline as Rac1 activate ribosomal ATPase and has the roles of regulating neurite growth through producing AMP potentiates bFGF-induced neurite outgrowth in PC12 cells through activating OPA1 repairs (upon GTPase effect ) which regulate the G-prorein-GTP- gamma, beta, and alpha productions that activate PLCs and IFNs for anti-inflammatory processes and growth .
Where, AMP is the primary results from Rac1 through Rac1 effect by the releasing of ATPase on inflammatory sources for producing long fatty chains then for stimulating OPA1 for producing GP-GTP subunits for ribosomes and Gactin repair. That as Rac1 is S6K rich Proline (that can act as "T-RNA) that can activate ribosomes and Gactin filaments through releasing ATPase and GTPase synthesis , as Rac1 activate both ATPase and GTPase which activate and correlate the activation of long fatty acids chains through its effect on anti-inflammatory source then will be followed by OPA1 enzymes activities for producing Acyl-COAs isoforms (gamma, beta, and alpha) which produced upon Rac1-GTPase effects for activating OPA1 for producing the three subunits Gp-GTP-Gamma, Gp-GTP-beta Gp-GTP-alpha upon OPA1 enzymes oxydative processes which necessary for rebuilding neuronal growth through activating both PLCs and IFNs productions necessary for anti-inflammatory growth, where proper Rac1 molecules and both PLCs and IFNs are necessary for sestrins synthesis but with availability of Proline, Tyr, Leu, Ser in the main Rac1 molecules (that will be described later) .
Proper Rac1 rich Proline and its necessary hydrophobic acids can be directed to ribosomes for repair and for ATPase productions and then for promoting GTPase production where GTPase can bind to Rac 1 as a Rac1-GTPase to stimulate β-catenin-dependent transcription of Wnt target genes.
Actually, the Beta-catenin is the central component of the Wnt signaling pathway, that is regulated by effort of GTPase on repairing OPA1 the mediated by Gp GTP subunits synthesis that have the key role for the regulation of cell proliferation through PLCs and IFNs synthesis.
The effect of proper Rac1 on inflammatory source will produce ROS and phorbol ester (long fatty chains) upon the effect of ATPase , while GTPase synthesis will be released for activating mitochondrial OPA1 enzymes that will act on phorbol ester and long fatty chains for producing firstly the long fatty-acyl-CoA-synthetase "G-prorein-GTP-Gamma" active subunits with pyrimidines synthesis (upon synthetase effects) followed by G-prorein-Beta "GP-GTP-Beta " synthesis upon synthase effect then followed by G-prorein-GTP-alpha productions upon phospholipase effects on GP-GTP Beta, that fatty Acyl-COA-beta synthesis are so necessary for activating both PLCs, and IFNs isoforms synthesis then for G-actin functions , and for TXA2 synthesis upon Plcγ2 and BTK regulations .
PLC-gamma-1 (PLCγ1) synthesis promoted or mediated by Acyl-COA-gamma (Gp-GTP-gamma) production upon effect of OPA1-synthetase on long fatty chains (which firstly produced from effect of Rac1 on inflammatory sources) for producing Gp-GTP-gamma necessary for PLCγ1 productions and vice versa ( upon synthetase activity then will produce Acyl-COA-synthase "upon synthase effect ", where PLCγ1 necessary for PLC-beta and PLC-alpha synthesis (upon effect of synthase and phospholipase respectively) for nerve growth factor "NGF" synthesis , then for IFN-beta and IFN-alpha synthesis which are necessary for B-cell maturations and activating BTK and sestrin synthesis, where availability of Leu amino acids in specific percentage in Rac1 are so necessary for activating SESN2 synthesis and for activating BTK for B-cell maturations (mediated by Beta-catenin production upon OPA1 enzymes regulations ) for SESN2 synthesis, where SESN2 necessary for reactivating brain enkephalin tissue and immune functions through activating Leu and Met-pentapeptides for activating Enkephalin tissue for activating brain and for restore memories .
PKC activators, PMA or bryostatin 1 (bryostatin) stimulates the growth of long neurites.
PMA or bryostatin incubation followed by NGF production activates PKC isoforms delta-, and epsilon-leading to outgrowth of long neurites. 
That the activations of long fatty acids chains synthesis (upon ATPase Effects and presence of Proline in Rac1 on inflammatory sources) then followed by GTPase for activating OPA1 synthase oxidations for activating Acyl-COA beta (G-prorein-GTP-beta) synthesis which followed by the effects of phospholipase for NGF synthesis , for FGF and for Gp-GTP-alpha synthesis necessary for anti-inflammatory growth and for long neurites growth. That Rac1-GTPase ¬> Gp-GTP three subunits upon OPA1 enzymes oxidative processes ¬>imp for G-actin repair and necessary for the growth of long neurites.
Neurons ( nerve cells) can be considered also as fundamental units necessary for the brain activities and nervous system (that the activating nerve cells regulated by Rac1 and mediated by Gp GTP subunits production which necessary for PLCγ2 and IFN beta synthesis for NGF synthesis that necessary for SESN2 synthesis mediated by β-catenin ) , where Leu and Met pentapeptides are so important to be formed regulated by SESN2 productions for activating enkephalin functions for brain cells activities which responsible for receiving and re-creating new responds signals for reactivating G-prorein-GTP subunits motors commands for modulating anti-inflammatory responds and for restore memories . The Pathway of Proline synthesis from glutamate are so important for amino acids synthesis (regulated by aminotransferase and synthetase ) and are necessary to be involved in Rac1 molecules for strengthen activity of Rac1 for Gp GTP subunits synthesis through acting on inflammatory source by Rac1 through ATPase production for producing long fatty chains which upon the OPA1 effects will produce G-prorein-GTP-subunits which will regulate PLCs and IFNs synthesis necessary for increasing anti-inflammatory processes and growth mediated by β-cateninSynthesis and mediated by NGF synthesis.
Where, Extracellular glutamate secretion into brain tissue causes neurotoxicity and brain damage 
That, the extracellular glutamate accumulation indicate the deficiency in proline synthesis then reflect deficiency in amino acids synthesis and deficiency in aminotransferase activities, that the neurotoxicity and brain damage are due to deficiency in proline synthesis that can reflect deficiency in aminotransferase enzyme activities that lead to accumulation in glutamate in brain.
My note is the Neuroprotections by oxytocin (OT) in ischemia of various tissues has the function of the ability of improving amino acids synthesis that due to improving in proline synthesis and in aminotransferase enzymes activities that will lead to decreasing in the accumulated glutamate and will
lead to increasing in proper Rac1 synthesis which will lead to of proper acting by Rac1 on inflammatory source for producing long fatty chains and ROS that at the same time the Rac1 will activate GTPase production for activating OPA1 enzymes which will act on the primary long fatty chains for producing the three G-prorein-GTP subunits (fatty Acyl-COAs) isoforms which will activate both PLCs and IFNs productions which consequently will activate liver function through activating BTK for SESN2 synthesis mediated by β-Catenin synthesis.
Notice that SESN2 has the function of feeding and reactivating enkephalin brain tissue through promoting Leu and Met pentapeptides synthesis which are necessary for brain functions.
That the inhibition of pyrimidine synthesis regulated by availability of synthetase, and deficiency in Proline synthesis will lead to accumulation of glutamate in brain with inhibition in Rac1 synthesis which led to deficiency in aminotransferase enzymes and lead to neuron toxicity.
That, the activating of proper aminotransferase enzymes with availability of Proline and hydrophobic acids synthesis will activate the proper of Rac1 production and activate the running of Rac1 functions pathway including anti-inflammatory processes and growth, that Proline synthesis will prevent glutamate accumulation and will activate Rac1 functions for increasing the anti-inflammatory activity and anti-inflammatory growth and at the same time will increase liver function (mediated by NGF and by β-Catenin synthesis) for adopting the SESN2 synthesis for functioning fatty acids metabolism and reactivating brain functions and neuronal activity.
Where, as there are inhibition in Proline synthesis and in aminotransferase enzyme as will reflect accumulation of glutamate and deficiency in amino acids synthesis and will be the result of decreasing in proper Rac1 Biosynthesis which characterized by the presence of Proline and necessary hydrophobic acids as Tyr, Ser, and Leu (that Leu necessary for SESN2 synthesis and for Leu pentapeptides synthesis), where the deficiency in proline will improve the deficiency in cartilage synthesis, and deficiency in amino acids Biosynthesis including Tyr and Leu amino acids too (where, Proline are main regulator for amino acid synthesis upon amino-transferase function).
And also, Deficiency in Proline nucléotides triplets "ACC" will lead to accumulation of tryptophan "TGG" that will be result of increasing in Glu synthesis ((GAA - Glu <¬>CTT Leu GAG - Glu <¬> CTC leu )), but deficiency in synthetase functions will be result of decreasing in pyrimidine synthesis that will be the result of accumulation of purines in the form of amino acids as glutamate that will be the result of increasing in the accumulation of Glu synthesis "due to accumulation of purines".
Neuronal toxicity can reflect accumulation of glutamate due to deficiency in synthetase functions and also reflect unavailability of Proline in Rac1 molecules (which necessary for synthetase activities) that can lead to inhibition in proper Rac1 synthesis and will inhibit the stimulations of OPA1 enzymes activities that can reflect decreasing in the G-prorein-GTP productions (necessary for PLCs and IFNs synthesis) that will reflect decreasing in BTK and in SESN2 synthesis that will lead to accumulation of purines in the forms of "AGG" which is the increasing in Glu in brain (GAA, GAG Glu ) with inhibition or decreasing in Proline and in Leu amino acids , where Leu active amino acids are necessary for SESN2 synthesis and activities .
Both Asp & Glu are carrying imp functions for activating and promoting the Leu and Met pentapeptides synthesis for enkephalin tissue that the deficiency or inhibition in Proline, in Leu, and in synthetase will inhibit Asp synthesis but not Glu (which consists of only accumulated purines) that will be the result of decreasing or inhibition in SESN2 synthesis and will be the result of accumulation of purines in the form of Glu in brain with inhibition in Leu and Met pentapeptides synthesis lead to decreasing in enkephalin functions that will be result of immune toxicity and neuronal toxicity .
So immune toxicity characterized by decreasing or inhibition in synthetase with deficiency in Proline amino acids synthesis that will lead to accumulation of purines in the form of Glu, where, Proline necessary for synthetase functions which has the roles of pyrimidines synthesis for hydrophobic amino acids synthesis.
The Proline synthesis is so necessary for aminotransferase activities and for the amino acids synthesis that Proline deficiency will lead to accumulations of purines in the form of Glu amino acids in brain with decreasing or inhibition in pyrimidine synthesis in liver and in brain too.
Notice that Asp with triplets "GAT - GAC” connected to Meet for Met pentapeptides synthesis, But, Glu "GAA, GAG " are translated and connected with Leu (CTC) for Leu pentapeptides synthesis in brain, that when Proline and Leu inhibited will lead to accumulation of glutamate in brain.
Also, the Hepatic Encephalopathy and Hyperammonemia Produce Neuronal Communication Dysfunction due to inhibition in amino transferase activities and unavailability of Proline which can carry the function of improving Hyperammonemia Produce Neuronal Communication through running active amino acids synthesis and through improving SESN2 synthesis that will increase memories functions too. That hyperammonemia and hepatic failure induce alterations in glutamatergic neurotransmission.
The Hyperammonemia is mainly due to deficiency in Proline amino acids followed by deficiency in aminotransferase enzymes which reflects dysfunction in OPA1 stimulations that can increase the dysfunction in the long fatty Acyl-COAs synthesis that will be result of decreasing in the condensation of Acyl-COAs for SESN2 synthesis that will reflect decreasing in Leu amino acids synthesis and decreasing in Leu pentapeptides which necessary in enkephalin tissue in brain that will lead to dysfunction in neuro-transmission , decreasing in memories function , and in Neuronal Communication, that can reflect liver failure (failure in BTK and in PLCγ2) with accumulation in Glu in brain .
So, Deficiency in Pproline and in hydrophobic acids synthesis (with failure in synthetase functions) specifically in Tyr Leu, and in Ser that will reflect dysfunction in OPA1 activities that will be the result of decreasing in Acyl-COAs synthesis then in SESNs synthesis that reflects neuronal cytotoxicity with accumulation of glutamate "purines" amino acids .
So, the deficiency in the ornithine-δ-aminotransferase (important in the synthesis of amino acids, including Proline and Leu ) are the signs of Deficiency in Pproline synthesis from glutamate that the sign of immune toxicity and neuronal toxicity with accumulations of glutamate , and result of deficiency in sestrins-Leu Biosynthesis and lead to neuronal cytotoxic . 
That previous study indicate the imp roles of ornithine-δ-amino-transferase for Leu, Ser and Tyr synthesis where, the absence of that enzyme ornithine-δ-A-Trase will cause Glu accumulation and Hyperammonemia with dysfunction in neurotransmission in vivo that can lead to neuronal toxicity.
Accordingly, inactivation of Sestrins (gamma, beta, and alpha) genes in invertebrates resulted in diverse metabolic pathologies, including oxidative damage, fat accumulation, mitochondrial dysfunction. 
Because activation of SESNs synthesis requires activating OPA1 enzymes for Acyl-COAs, where activating OPA1 are running by Rac1 Rich-Proline, where unavailability of Proline will be result of Deficiency or decreasing in OPA1 repair, decreasing in hydrophobic acids synthesis and decreasing in cartilage synthesis followed by decreasing in PLCs synthesis.
That dysfunction in SESNs Biosynthesis will reflect dysfunction neuronal communication and transmission with Encephalopathy and Hyperammonemia due to mainly reductions in Rac1 rich Proline, and in aminotransferase enzymes that result of Deficiency in amino acids synthesis.
Notice , ornithine- aminotransferase "OAT" that regulated by ribosomes so by Rac1 as well, and is essential in creating ornithine from the Proline substrate for amino acids synthesis , so Proline is so necessary regulator as substrate for the synthesis of ornithine which is so necessary for hydrophobic amino acids synthesis that OAT gene is necessary for recover the Hyper-ammonemia through creating necessary Tyr, Ser, Leu hydrophobic amino acids for Rac1 synthesis, for OPA1 activities, for nuclear isoforms synthesis and for SESNs synthesis started by SESN-gamma "SESN1", then beta "SESN2", then alpha "SESN3" regulated by OPA1 synthetase, synthase, then phospholipase respectively.
So The immune toxicity defined as a dysfunction in both synthetase enzymes and in availability of Proline synthesis , where synthetase necessary for pyrimidine synthesis needed for amino acids synthesis, while Proline synthesis from glutamate are necessary for amino acids synthesis (regulated by aminotransferase) , that deficiency in synthetase will be the result of accumulating purines in the form of Glu but deficiency in proline will result for deficiency in amino acids synthesis that will be the result of the deficiency in OPA1 function and dysfunction in amino transferase activities which reflects
Hyperammonemia in vivo.
Also immune toxicity characterized by inhibition in kynurenine pathway and in tryptophan "TGG” (due to inhibition in synthetase activity) which is essential amino acid used for building protein, also immune toxicity characterized by inhibition in PLCγ1 and PLCγ2 where both regulated by OPA1 enzymes effects that consequently will reflect Inhibition in TXA2 synthesis (which regulated by PLCγ2 functions) . Inhibition in thymine pyrimidine synthesis will be result in the inhibition in tryptophan TGG that will be result of accumulation in Thr amino acids ACC "purines" in blood and will inhibit Proline ACC synthesis (where, Proline synthesis is connected to the availability of tryptophan TGG in vivo.
Sestrin has necessary roles connected with Leu amino acid synthesis (which considered previously as regulated by Proline and then by aminotransferase) for running and functioning metabolic process for preventing reverse reactions, where absence of ornithine-δ-aminotransferase enzymes can lead to dysfunction in hydrophobic amino acids and Proline synthesis and consequently will reflect dysfunction in OPA1 stimulation and activities ,that lead to pathogenic Encephalopathy and Hyperammonemia in vivo and dysfunction in neuronal Communication and transportation .
The dysfunction in pyrimidine synthesis regulated by synthetase lead to accumulations of purines in the form of Glu amino acids in brain and deficiency in synthetase can lead to deficiency in proline that will lead to deficiency in Ornithine synthesis (regulated by amino transferase enzymes ) which formed from Proline lead to deficiency in hydrophobic amino acids synthesis, that lead to deficiency in Tyr, Ser including Leu (CTC "Leu"&TTC "Leu" ) that will reflect dysfunction in SESN2 synthesis and will be result of accumulation in Glu ("GAG" & GAA "Glu") that will be result of dysfunction in neuronal Communication (and transportation) and pathogenic Encephalopathy. factors NRF2 and NF-κB are coordinated effectors of the Rho family, GTP-binding protein RAC1 during inflammation, that RAC1 induces NRF2 signaling pathway. 
That, nuclear transcription factor "NTF" are basically formed due to the effects of Rac1 on inflammatory sources by producing ATPase and GTPase for analysis inflammations for producing long fatty chains that will produce nuclear fatty Acyl-COAs isoforms upon the effects of OPA1 (which activated by GTPase) that will be followed BY NTF synthesis and then will stimulate PLCs and IFNs synthesis for running anti-inflammatory responds and anti-inflammatory growth .
Remember that S6K rich Proline are the basis for Rac1 Which are necessary for activating OPA1 synthetase and other OPA1 enzymes for producing fatty Acyl-COAs "nuclear transcription factors " which coordinate analysis the inflammation molecules for finally increasing anti-inflammatory processes and growth including TXA2 synthesis regulated by PLCγ2 and BTK.
Where, negative Rac1 inhibits the development of NK cell–mediated cytotoxicity by two mechanisms. There is a rapid increase in Vav tyrosine phosphorylation during the development of antibody-dependent cellular cytotoxicity and natural killing. 
Indicating that OPA1 oxidative phosphorylation are basis for development of antibody-dependent cellular cytotoxic
For fast running FOX regulated by OPA1 for fatty Acyl-COAs isoforms (the three G-prorein subunits Gp-gamma, Gp-beta, and Gp-alpha) for running their own pathways for producing proper PLCs and IFNs for running proper anti-inflammatory activities and anti-inflammatory growth f