Citric acid cycle: A cell has a high demand for ATP and the energy charge in the
ID: 93138 • Letter: C
Question
Citric acid cycle: A cell has a high demand for ATP and the energy charge in the cell is low. The rate of oxidation of acetyl-CoA, and hence the production of ATP by oxidative phosphorylation, is affected by the overall concentration of the intermediates present in the citric acid cycle.
Under these conditions:
a. What effect would a HIGH concentration of intermediates have on the rate of entry of acetylCoA into the cycle? (1 mark)
b. What effect would a LOW concentration of intermediates have on the rate of entry of acetylCoA into the cycle? (1 mark)
c. How can the concentration of the citric acid cycle intermediates be increased? Give one instance (3 marks)
Explanation / Answer
a.
Increasing the NADH/NAD+, acetyl CoA/CoA, or ATP/ADP ratio promotes phosphorylation and deactivation of the complex. Means high concentrations of immediate (acetyl CoA and NADH) and ultimate (ATP) products inhibit the activity.
B.in case of low.
pyruvate as well as ADP (a signal of low energy charge) activate the dehydrogenase by inhibiting the kinase.
The intermediates of the citric acid cycle are present at micromolar concentration in blood and are regulated by respiration, metabolism and renal reabsorption/extrusion.
GPR91 a previously orphan G-protein-coupled receptor (GPCR), functions as a receptor for the citric acid cycle intermediate succinate. GPR99 a close relative of GPR91, responds to -ketoglutarate, another intermediate in the citric acid cycle. Thus by acting as ligands for GPCRs, succinate and -ketoglutarate are found to have unexpected signalling functions beyond there roles.
Furthermore, we show that succinate increases blood pressure in animals. The succinate-induced hypertensive effect involves the renin–angiotensin system .
GPR91 in renovascular hypertension, a disease closely linked to atherosclerosis, diabetes and renal failure.