Question

During clinical rounds, you encounter patients who exhibit defects that affect gluconeogenesis. Predict the effect that each of the following conditions/defects would have on gluconeogenesis. Explain your prediction and indicate what life style change the patient might make to alleviate the symptoms.

a) Patient 1 exhibits a deficiency of the liver lactate dehydrogenase activity.

b) Patient 2 exhibits defective liver glucagon receptors which cannot bind glucagon.

c) Patient 3 exhibits a constitutively phosphorylated liver phosphofructokinase-2 to lock the bifunctional enzyme into its fructose 2,6-bisphosphatase (hydrolase) activity. This results in cellular levels of fructose- 2,6-bisphosphate that are undetectable in the liver cells.

Answer 1

Lactate dehydrogenase is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD⁺ to NADH and back. Thus in the absence of liver lactate dehydrogenase activity, affects how the body breaks down sugar for use as energy in cells. The interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD⁺ would, therefore, stop affecting energy metabolism.

Glucagon's role in the body is to prevent blood glucose levels dropping too low. To do this, it acts on the liver in several ways: It stimulates the conversion of stored glycogen (stored in the liver) to glucose, which can be released into the bloodstream. This process is called glycogenolysis. But for all this glucagon secreted from pancreas must bind to its receptors located in its target gland liver and if it is unable to bind to its receptors in the liver the level of blood glucose will become too low.

Depending on which domain is stabilized, PFK-2 will synthesize or degrade fructose-2,6-bisphosphate, which impacts rates of glycolysis. Thus this function would be disturbed.