I have already mentioned the importance of the NADH/NAD
in determining thedirection of equilibrium between lactate and pyruvate. In our discussion of glycogenformation and breakdown, I have also asked you to refer to the information in your textregarding the regulation of glycogen phosphorylase. You can safely assume that thosefactors that favor activation of this enzyme inhibit – directly or indirectly – the action of glycogen synthase.
Please read and understand the main points of metabolicregulation discussed on pages 852-862 in your Devlin text for the next exam.
Themain take home message that I want you to understand regarding hormones is thatconcerning insulin and glucagon.
(You are not responsible for all the details of enzyme regulation by hormones, and allosteric regulators etc, but you need to knowthe main points. I leave that to your judgement.)
We must, however, understand thatinsulin levels normally rise in the blood in response to a meal with carbohydrates.Glucagon levels concomitantly fall. Common sense would tell us then that increasedinsulin levels would not favor high glucose production from gluconeogenesis or fromglycogen breakdown. Rather, glycolysis would be favored, as would the Kreb’s cycle.However, after a point where ATP levels were high, the pyruvate dehydrogenase enzyme(that forms acetyl CoA from pyruvate) would be deactivated by abundant ATP. Thiswould necessitate a shift toward triglyceride formation – the subject of the future lipidlecture material. Indeed, insulin favors triglyceride formation in the adipose tissue,especially when carbohydrate intake is excessive beyond need. Obviously, what I justnoted about the effects of increased insulin levels would be generally antagonized byhigh glucagon levels. For example, insulin simulates glucose transporters in manytissues, whereas glucagon does not. Also, two important enzymes that help driveglycolysis are glucokinase (step # 1) and pyruvate kinase (where pyruvate is formed fromPEP). Both enzymes are activated by way of the action of insulin. Glucagon has theopposite effect upon their activity.
Some further points on the reciprocity of gluconeogenesis and glycolysis
and TheirInter-related Control Systems
These two pathways are coordinated so that they roughly reciprocally active. Now with both pathways balancing out regarding energy usage vs. energy given off (ex two ATP produced in glycolysis), there is no thermodynamic impediment to then not going on afull speed simultaneously. In fact, both are exergonic. However, the amounts and theactivities of the enzymes of both pathways are so controlled that they do not activate fullyat the ame time. Remember, the rate of glycolysis is also controlled by the amount of glucose and the rate of gluconeogenesis by the amount of its available precursors, such aslactate.We have not discussed in lecture how stringently controlled the conversion of fructose-1-P to fructose-1,6-bisphosphate (F-1,6-BP) is during glycolysis. Whereas AMPstimulates phosphofructokinase (the enzyme that puts the second phosphate on fructoseduring glycolysis), ATP and citrate inhibit it. For example, high AMP levels indicate thatenergy levels are low, and that there is need for ATP production from glycolysis. Theconverse is also true for high levels of ATP and citrate.