The activity of which of the following enzymes is directly affected by citrate?
High-Yield Explanation
Citrate is produced by citrate synthase from acetyl CoA and oxaloacetate. This reaction takes place in the mitochondria, but citrate can move freely from the mitochondria into the cytosol. When the citric acid cycle slows down, citrate accumulates. In the cytosol, it acts as a negative allosteric regulator of phosphofructokinase I, the enzyme that catalyzes the committed step of glycolysis. Fructose-2,6-bisphosphatase breaks down fructose-2,6-bisphosphate, a potent allosteric activator of phosphofructokinase I. Fructose-2,6-bisphosphatase is activated by cyclic AMP-dependent protein kinase. Isocitrate dehydrogenase conves isocitrate to alpha-ketoglutarate in the citric acid cycle. It is allosterically stimulated by ADP and inhibited by ATP and NADH. This reaction produces NADH and CO2. Pyruvate carboxylase is a mitochondrial enzyme that conves pyruvate to oxaloacetate. It is impoant in gluconeogenesis and replenishes the oxaloacetate in the citric acid cycle. Ref: Bender D.A., Mayes P.A. (2011). Chapter 20. Gluconeogenesis & the Control of Blood Glucose. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper's Illustrated Biochemistry, 29e.