In 2017, it was discovered that naked mole rats ( Heterocephalus glaber ) could
ID: 3164644 • Letter: I
Question
In 2017, it was discovered that naked mole rats (Heterocephalus glaber) could survive up to 18 minutes in an anoxic (0% oxygen) environment without any permanent damage to the organism. The normal body temperature of naked mole rats is 30°C, making them poikilothermic animals that are able to operate at a range of body temperatures and to alter its body temperature based upon the environment. Even if the animals are warmed to 37°C, they still survive 6 minutes in an anoxic environment, which is still more than 5 minutes longer than the survival of other rodents like mice. You are already familiar with the H. glaber hemoglobin, but as usual, this does not fully explain the naked mole rat ability to survive anoxia.
Blood glucose concentrations during anoxia were found to be similar in mice and mole rats, but during normoxic (normal oxygen levels) conditions, naked mole rate had a blood glucose concentration of 3.49mM while mice had 6.66mM, making them appear hypoglycemic compared to other rodents and mammals.
PFK-1 was found to be inhibited by low pH conditions. However, this inhibition is non-existent when fructose 2,6-bisphosphate is present. Consider what you already know about the regulation of PFK-1 by F26BP and also consider the following figure. Note that bisphosphoglycerate mutase activity increases with [H+] and that 2,3-bisphosphoglycerate phosphatase activity decreases with [H+]. Explain how pH, 2,3-BPG and F26BP work together to regulate flux through glycolysis and hemoglobin function. Explain why it makes sense that F26BP is the master regulator rather than pH for PFK-1. You may want to think about the situation where oxygen is depleted and then what changes when oxygen returns to the system.
Explanation / Answer
F26BP allosterically regulates pfk1. DURING anoxic condition oxygen supply is not available. Hence pH of the body goes down as hemoglobin cannot supply oxygen to the tissues.Glycolysis rate increases but when pH goes very low pfk1 gets inhibited. Presence of f26bp leads to strong activation of glucose breakdown (Glycolysis) as f26bp is an allosteric regulator of pfk1 and formation of lactic acid that reduce pH.23 bisphosphoglycerate mutase gets activated and formation of 23bpg take place.this activates 3 phosphoglycerate which in turn is a byproduct of Glycolysis. Glucose breakdown continues . pfk1 gets modulated and increased glucose breakdown happens. This does not happen in case of normoxic environment where sufficient oxygen is available for citric acid cycle.
The citric acid cycle is shunted in anoxic conditions.
Formation of f26bp leads to modulation of pfk1 via allosteric regulation ,reduction in pH which again controls another enzyme called bpg mutase and formation of 23bpg takes place to carry on glucose breakdown via phosphatase activity.However it also binds to hemoglobin with a high affinity and helps in releasing oxygen in local tissues that require it. F26BP can be considered master regulator as it effects Glycolysis, pfk1 activity and pH reduction of the system during anoxic condition.