Singulair Glucose Utilization, Glycolytic Pathway, Glyconeogenesis, Energy Metabolism, Correct Time

Why the brain function is impaired due to Singulair????? Maybe.

Here is the last chapter in a theoretical reason why Singulair affects brain function thus causing anxiety, depression, agitation, aggression, ADD/ADHD, and in extreme situations maybe seizures. I presented the study of the Chinese researchers that show a direct link between the cysLT1 receptor and the astrocyte in the brain. We don't really know how the cysLT1 receptor interacts with receptors that control astrocytes under all circumstances. We just know that there is an important link.

So last night, I had a dream about astrocytes. I don't really have anything to do but sit on an island, look at the Caribbean and fish so mental stimulation is actually welcome.

The last part of the "chain reaction" is probably the astrocytes role in glyconeogenesis. In other words, when the brain does not get proper nutrition, it sends signals to the liver to do something about the problem. The liver in turn releases glycogen which is turned into glucose to be released into the blood stream. A very unhappy brain becomes a very relieved brain. Obviously, we can't be eating all day long to keep our blood sugar up so the liver has to store energy and release it at the correct time.

Here is a diagram of that. Astrocytes are the only cell that produce the proper chemicals for this process to happen.

http://www.nature.com/jcbfm/journal/v27/n2/fig_tab/9600343f5.html
FIGURE
Quote: All credit to the authors, of course.

Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis
Leif Hertz, Liang Peng and Gerald A Dienel

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Glucose utilization pathways that provide or consume ATP. (A) Schematic of key aspects of the glycolytic pathway of glucose utilization for energy metabolism and major branch points that can divert carbon for other uses, including NADPH generation, storage of glucosyl units in glycogen, neuromodulator, and amino acid and nucleotide biosynthesis. The most important reactions for generation of energy are glycolysis (pyruvate/lactate formation from glucose), shown in light brown and occurring in all cell types, and glycogenolysis (pyruvate/lactate formation from glycogen), shown in light green, which occurs only in astrocytes, due to the astrocyte-specific expression of the enzyme glycogen phosphorylase, which releases a glucosyl unit from glycogen as G1P. The energetically most important biosynthetic reactions are synthesis of glycogen from glucose (glycogenesis) shown in brown and green and from pyruvate/lactate (gluconeogenesis) shown in pink, brown, and green. Gluconeogenesis is also astrocyte-specific, because only astrocytes express fructose-1, 6-bisphosphatase, which generates F6P from fructose-1, 6-bisphosphate (F1, 6P) and PC, which generates oxaloacetate (OAA) from pyruvate. The latter reaction is followed by formation of phosphoenolpyruvate (PEP) by decarboxylation of OAA; this sequence is necessary to form PEP from pyruvate, an energetically unfavorable reaction. Biosynthesis of serine/glycine (shown in olive) is also an astrocyte-specific process due to preferential expression of 3-phosphoglycerate dehydrogenase (Yamasaki et al., 2001). Both neurons and astrocytes form alanine and ribose-5-phosphate (R5P), the latter in the pentose shunt pathway (upper left corner), linked to NADPH production needed for operation of glutathione peroxidase and oxidation of monoamine transmitters. The MAS, indicated by red, transfers malate formed in the cytosol from oxaloacetate during conversion of NADH to NAD+ into mitochondria. PDH-mediated formation of acetyl CoA, which is also shown in red, initiates oxidative degradation of pyruvate in the mitochondria. Red and blue text for ATP indicates energy production and utilization, respectively. (B) Major reactions and net ATP yields or net ATP consumption of major pathways derived from the glycolytic pathway are indicated in color-coded boxes that correspond to the color-coded pathways in panel A. For simplicity, the scheme indicates the energy yields (ATP) and NAD(P)H production or utilization based on metabolism of 1 glucose to form one ribulose-5-P, two lactate/pyruvate, or 2 serine; a similar representation illustrates the energy and cofactors required for gluconeogenic conversion of two moles of lactate into one free (G6P) or glycogen-bound glucosyl unit. Glc, glucose; P, phosphate; G6P, glucose-6-P; 6PG, 6-P-gluconate; R5P, ribulose-5-P; GSH, reduced form of glutathione; GSSG, oxidized form of glutathione; F6P, fructose-6-P; F1, 6-P, fructose-1, 6-bisphosphate; GAP, glyceraldehyde-3-P; DHAP, dihydroxyacetone-P; 3PG, 3-P-glycerate; 2PG, 2-P-glycerate; PEP, phosphoenolpyruvate; Pyr, pyruvate; Lac, lactate; Ala, alanine; OAA, oxaloacetate; 3P-HyPyr, 3-P-hydoxypyruvate; Glu, glutamate; KG, -ketoglutarate; 3P-L-Ser, 3P-L-serine; L-ser, L-serine; D-ser, D-serine; Gly, glycine; C1, one carbon fragment used for methyl donor reactions.

This is quite interesting because should the connection between the cysLT1 receptor and astrocyte be established and explained, it shows that there is a very direct link between the immune system and metabolism. That should be intuitive because when we get seriously sick, then we are laying in bed and the body should try to conserve energy so that we don't just waste away.

So what happens if we cause changes in the cysLT1 receptor to cause the astrocytes to believe that we are sick, the normal connection between the brain and glyconeogenesis then doesn't exist. We would have to be causing some kind of periods of extreme stress on the brain because we are out moving around and doing not home sick in bed.

Maybe we should award the Chinese researchers the nobel prize? Maybe they established the connection between the immune system and metabolism? Is there also a link between the immune system of some individuals and depression? Some how, this makes perfect sense. So we have to find out and help as many people as we can.

I think that it is time to call the lawyer-biochemists to find out if this can be proven to be true and if Merck knew or not.