The rise in epinephrine mediates the twitching, which is a result of the adrenergic response to hypoglycemia. Tremor and sweating are included in the adrenergic response. Seizures, coma, and death can occur due to impaired brain function resulting from neuroglycopenia, which is the impaired delivery of glucose to the brain. Neuroglycopenic symptoms develop if hyperglycemia persists.

Detergents are amphipathic molecules with both hydrophilic (polar) and hydrophobic (nonpolar) regions. They disrupt membrane structure by solubilizing membranes. If the issue were the translocase required for moving the glucose 6-phosphate substrate into the ER rather than the phosphatase, disrupting the ER membrane would allow the substrate access to the phosphatase.

In hypoglycemia, glucagon, a peptide hormone released from pancreatic α cells, binds to its plasma membrane G protein–coupled receptor on hepatocytes. The associated trimeric G protein's αs subunit is activated, separating from the β and γ subunits. It then activates adenylyl cyclase, which generates cyclic adenosine monophosphate (cAMP) from ATP. Protein kinase A (PKA) is activated by cAMP, which in turn phosphorylates and activates glycogen phosphorylase kinase. This leads to the activation of glycogen phosphorylase. Glycogen degradation occurs, generating glucose 1-phosphate, which is converted to glucose 6-phosphate. In cases of glucose 6-phosphatase deficiency, the degradative process stops at this point, making administration of glucagon ineffective. Epinephrine would also have a similar effect.

The rise in glucose 6-phosphate upregulates glycolysis, leading to a decrease in the availability of inorganic phosphate (Pi) as it becomes trapped in phosphorylated glycolytic intermediates. The trapping of Pi decreases the ability to phosphorylate adenosine diphosphate (ADP) to ATP, resulting in a fall in ATP levels. This causes a rise in adenosine monophosphate (AMP), which is then degraded to urate. The rise in glucose 6-phosphate also drives the pentose phosphate pathway, increasing the production of ribose 5-phosphate from ribulose 5-phosphate and leading to an increase in purine synthesis. The elevated purines are degraded to urate. Glycogen phosphorylase activity is reduced due to the decrease in Pi, resulting in increased glycogen storage with normal structure. Lactate levels increase as the decrease in ADP phosphorylation to ATP leads to a decrease in cellular respiration. This prevents the oxidation of reduced nicotinamide adenine dinucleotide (NADH) from glycolysis by Complex I of the electron transport chain. Instead, cytosolic lactate dehydrogenase oxidizes NADH while reducing pyruvate to lactate. Pyruvate levels increase due to the increased glycolysis. The ionization of lactate releases protons (H+), causing a metabolic acidosis characterized by low pH due to increased acid production. Respiratory compensation results in an increased respiratory rate.
TQ1.The twitching is the result of the adrenergic response to hypoglycemia and is mediated by the rise in epinephrine. The adrenergic response includes tremor and sweating. Neuroglycopenia (impaired delivery of glucose to the brain) results in impairment of brain function that can lead to seizures, coma, and death. Neuroglycopenic symptoms develop if the hyperglycemia persists. TQ2.Detergents are amphipathic molecules (that is, they have both hydrophilic [polar] and hydrophobic [nonpolar] regions). Detergents solubilize membranes, thereby disrupting membrane structure. If the problem were the translocase needed to move the glucose 6-phosphate substrate into the ER, rather than the phosphatase, disruption of the ER membrane would allow the substrate access to the phosphatase. TQ3.Glucagon, a peptide hormone released from pancreatic α cells in hypoglycemia, binds its plasma membrane G protein–coupled receptor on hepatocytes. The αs subunit of the associated trimeric G protein is activated (guanosine diphosphate is replaced by guanosine triphosphate), separates from the β and γ subunits, and activates adenylyl cyclase that generates cyclic adenosine monophosphate (cAMP) from ATP. cAMP activates protein kinase A (PKA) that phosphorylates and activates glycogen phosphorylase kinase, which phosphorylates and activates glycogen phosphorylase. The phosphorylase degrades glycogen, generating glucose 1-phosphate that is converted to glucose 6-phosphate. With glucose 6-phosphatase deficiency, the degradative process stops here (see figure below). Consequently, administration of glucagon is unable to cause a rise in blood glucose. [Note: Epinephrine would be similarly ineffective.]
TQ4.The availability of inorganic phosphate (Pi) is decreased because it is trapped as phosphorylated glycolytic intermediates as a result of the upregulation of glycolysis by the rise in glucose 6-phosphate. Urate is elevated because the trapping of Pi decreases the ability to phosphorylate adenosine diphosphate (ADP) to ATP, and the fall in ATP causes a rise in adenosine monophosphate (AMP). The AMP is degraded to urate. Additionally, the availability of glucose 6-phosphate drives the pentose phosphate pathway, resulting in a rise in ribose 5-phosphate (from ribulose 5-phosphate) and, consequently, a rise in purine synthesis. Nicotinamide adenine dinucleotide phosphate (NADPH) also rises. Purines made beyond need are degraded to urate (see figure on the next page). [Note: The decrease in Pi reduces the activity of glycogen phosphorylase, resulting in increased storage of glycogen with a normal structure.] Lactate is elevated because the decrease in phosphorylation of ADP to ATP results in a decrease in cellular respiration (respiratory control) as a result of these processes being coupled. As a consequence, reduced nicotinamide adenine dinucleotide (NADH) from glycolysis cannot be oxidized by Complex I of the electron transport chain. Instead, it is oxidized by cytosolic lactate dehydrogenase with its coenzyme NADH as pyruvate is reduced to lactate. [Note: Pyruvate is increased as a result of the increase in glycolysis.] The lactate ionizes, releasing protons (H+) and leading to a metabolic acidosis (low pH caused here by increased production of acid). Respiratory compensation causes an increased respiratory rate.