One of the proposed metabolic roles of lactate involves a me…
One of the proposed metabolic roles of lactate involves a metabolite shuttle between two types of cells within the brain. Glu is the primary excitatory neurotransmitter in the brain. The proposed shuttle system is shown in an illustration from the above-mentioned article and depicts, among other things, the recycling of Glu. Image Description This picture depicts a chain of events that occurs in and between a glutaminergic neuron and an astrocyte, two types of cells within the brain. Two different reaction cycles are shown. In the first, La (lactate) begins in the astrocyte. It is able to pass out of the astrocyte and into the glutaminergic neuron. There, in the presence of LDH (lactate dehydrogenase), lactate is converted into Pyr (pyruvate). Here the two reaction cycles intersect with each other. In the presence of AAT (alanine amino transferase), pyruvate is converted into Ala. Simultaneously, this allows Glu in the glutaminergic neuron to be converted into 2-oxoglutamate. The Ala is then able to pass out of the glutaminergic neuron and back into the astrocyte. In the astrocyte, the entire process is reversed. Ala is converted back into pyruvate in the presence of AAT, allowing 2-oxoglutamate in the astrocyte to simultaneously be converted into Glu. Pyruvate is then converted back into lactate in the presence of lactate dehydrogenase. At this point, the cycle repeats. In the second cycle, Glu begins in the glutaminergic neuron. It is able to pass out of the glutaminergic neuron and into the astrocyte. There, in the presence of an unnamed enzyme, NH4- is added to Glu to create Gln. The NH4- was provided by converting the Glu produced in the previous cycle (through conversion of Ala into pyruvate) back into 2-oxoglutamate in the presence of GDH (glutamate dehydrogenase). This creates a new 2-oxoglutamate that can be converted into Glu again the next time the first cycle brings Ala into the astrocyte. Meanwhile, the Gln that was created by the addition of NH4- is able to pass out of the astrocyte and into the glutaminergic neuron. There, the entire process is reversed. Gln is converted back into Glu and a free NH4- in the presence of an unnamed enzyme. This regenerates the Glu in the glutaminergic neuron that began this cycle. Meanwhile, the released NH4- is added back to a 2-oxoglutamate by glutamate dehydrogenase, re-forming the Glu that was transformed into 2-oxoglutamate in the first reaction cycle when pyruvate in the glutaminergic neuron was converted into Ala. The cycle then is able to repeat. What is the advantage gained by the glutamatergic cell in shuttling lactate when it appears that a pyruvate shuttle would be more direct? (1 pt.) What role does Ala play in the shuttle system? Again it appears that shuttling pyruvate would be more direct. (1 pt.) Gln is the amino acid with the highest circulating concentration in the blood. What major role does it play in nitrogen metabolism? (1 pt.) The article by Gladden cited in the previous question talks about ATP control of glycolysis. Give the name of one enzyme in the citric acid cycle that is controlled by ATP or ADP/AMP levels. (1 pt.) “Increased nervous system activity requires increased energy metabolism in neurons. The conventional view is that neuronal energy metabolism is fuelled by glucose oxidation (Chih et al. 2001). The action potentials of neuron activity result in Na+ entry and K+ efflux which activates Na+-K+ -ATPase in the neuronal plasma membrane; this ATPase pump activity, in turn, leads to decreased ATP, increased ADP, increased Pi, and increased AMP, standard activators of glycolysis, the TCA cycle and mitochondrial oxidative phosphorylation. ATP synthesis will increase via these energetic pathways with a concomitant utilization of intracellular glucose that lowers glucose, leading to…” Acetyl CoA and Glu can react to form N-acetyl Glu, which is a potent activator of the enzyme glutamate dehydrogenase. Briefly explain why this compound is well-suited to regulate the activity of this enzyme. (2 pts.)
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