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Physical activity produces an increased energy requirement in the muscles as well as in the brain. During periods of intense exercise, glycogenolysis is activated in muscles to provide them with the energy needed for contractions, and research indicates that astrocytes also consume glycogen at increased levels during exercise. It is hypothesized that during periods of physical exertion, astrocytes convert glycogen to lactate, which is then used as a fuel source in neurons.Monocarboxylate transporters (MCTs) are responsible for the movement of lactate across membranes, and MCT2 is expressed at increased levels in neuronal cells during exercise. Scientists proposed that lactate is secreted from astrocytes and taken up by neurons through MCT2. Lactate is then converted to pyruvate and enters the mitochondria, where it is further metabolized. To test their predictions, scientists examined the effect of exercise on glycogen metabolism in rodents.Experiment 1Rats were either allowed to rest or exercised to exhaustion. The levels of several metabolites were then quantified in both the plantaris muscle and the hippocampus.
Figure 1 Levels of several metabolites in plantaris muscle (A) and hippocampus (B) from rats at rest or after exercising to exhaustionExperiment 2Rats were injected with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) or saline, and glycogen and lactate levels were measured in the hippocampus of rats at rest or after exercise to exhaustion.
Figure 2 Levels of glycogen (A) and lactate (B) in rats injected with DAB or saline, after rest or upon exhaustion
Adapted from Matsui T, Omuro H, Liu Y-F, et al. Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity. Proceedings of the National Academy of Sciences. 2017;114(24) :6358-6363.
-DAB most likely inhibits which reaction?

Question

Passage
Physical activity produces an increased energy requirement in the muscles as well as in the brain. During periods of intense exercise, glycogenolysis is activated in muscles to provide them with the energy needed for contractions, and research indicates that astrocytes also consume glycogen at increased levels during exercise. It is hypothesized that during periods of physical exertion, astrocytes convert glycogen to lactate, which is then used as a fuel source in neurons.Monocarboxylate transporters (MCTs) are responsible for the movement of lactate across membranes, and MCT2 is expressed at increased levels in neuronal cells during exercise. Scientists proposed that lactate is secreted from astrocytes and taken up by neurons through MCT2. Lactate is then converted to pyruvate and enters the mitochondria, where it is further metabolized. To test their predictions, scientists examined the effect of exercise on glycogen metabolism in rodents.Experiment 1Rats were either allowed to rest or exercised to exhaustion. The levels of several metabolites were then quantified in both the plantaris muscle and the hippocampus.

Figure 1 Levels of several metabolites in plantaris muscle (A) and hippocampus (B) from rats at rest or after exercising to exhaustionExperiment 2Rats were injected with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) or saline, and glycogen and lactate levels were measured in the hippocampus of rats at rest or after exercise to exhaustion.

Figure 2 Levels of glycogen (A) and lactate (B) in rats injected with DAB or saline, after rest or upon exhaustion
Adapted from Matsui T, Omuro H, Liu Y-F, et al. Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity. Proceedings of the National Academy of Sciences. 2017;114(24) :6358-6363.
-DAB most likely inhibits which reaction?

Quizplus · Accepted Answer

11ecba2d_0ed4_e254_a3bf_6faf99ad1113_MD0008_00 Glycogen is primarily composed of several glucose units linked to each other through α-1,4-glycosidic bonds. Degradation of glycogen begins with a process called phosphorolysis, which removes individual glucose subunits. The enzyme glycogen phosphorylase, which catalyzes this reaction, breaks the α-1,4 bond by adding inorganic phosphate at carbon 1 of the terminal glucose unit. As a result, glucose in the form of glucose-1-phosphate (G1P) is released from glycogen stores. Figure 2A shows that after exercise to exhaustion, glycogen stores in the hippocampus are partially depleted. When DAB is injected, glycogen is depleted to a lesser extent. This suggests that DAB prevents glycogen degradation. Of the choices presented, inhibiting phosphorolysis is the only option that will lead to decreased glycogen degradation. (Choice A) Phosphorylated glucose in the form of glucose-6-phosphate (G6P) is generated during glycogen degradation by phosphorolysis and isomerization, or during glycolysis by phosphorylation. Inhibiting phosphorylation of glucose (catalyzed by hexokinase) would deplete the amount of G6P available. As a consequence, glycogen degradation would most likely increase to replenish the G6P needed for glycolysis and fermentation. Figure 2A shows that DAB causes glycogen degradation to decrease instead. (Choice C) Inhibition of lactate export would cause an increase in lactate concentration. Figure 2B shows that lactate is present at decreased levels in rats treated with DAB. This is most likely because less glycogen was degraded for use in lactate synthesis, as indicated by Figure 2A. (Choice D) Figure 2 indicates that DAB inhibits glycogenolysis. However, the first step in glycogenolysis breaks a bond in glycogen by adding inorganic phosphate across it (phosphorolysis) rather than by adding water across it (hydrolysis). Educational objective: Glycogen is primarily composed of several glucose subunits bound together by α-1,4 glycosidic linkages. Glycogen is cleaved into glucose-1-phosphate subunits by glycogen phosphorylase in a reaction called phosphorolysis. Phosphorolysis breaks bonds by adding an inorganic phosphate group across them.

Passage Physical Activity Produces an Increased Energy Requirement in the Muscles