<P> Citrate is used for feedback inhibition, as it inhibits phosphofructokinase, an enzyme involved in glycolysis that catalyses formation of fructose 1, 6 - bisphosphate, a precursor of pyruvate . This prevents a constant high rate of flux when there is an accumulation of citrate and a decrease in substrate for the enzyme . </P> <P> Recent work has demonstrated an important link between intermediates of the citric acid cycle and the regulation of hypoxia - inducible factors (HIF). HIF plays a role in the regulation of oxygen homeostasis, and is a transcription factor that targets angiogenesis, vascular remodeling, glucose utilization, iron transport and apoptosis . HIF is synthesized consititutively, and hydroxylation of at least one of two critical proline residues mediates their interaction with the von Hippel Lindau E3 ubiquitin ligase complex, which targets them for rapid degradation . This reaction is catalysed by prolyl 4 - hydroxylases . Fumarate and succinate have been identified as potent inhibitors of prolyl hydroxylases, thus leading to the stabilisation of HIF . </P> <P> Several catabolic pathways converge on the citric acid cycle . Most of these reactions add intermediates to the citric acid cycle, and are therefore known as anaplerotic reactions, from the Greek meaning to "fill up". These increase the amount of acetyl CoA that the cycle is able to carry, increasing the mitochondrion's capability to carry out respiration if this is otherwise a limiting factor . Processes that remove intermediates from the cycle are termed "cataplerotic" reactions . </P> <P> In this section and in the next, the citric acid cycle intermediates are indicated in italics to distinguish them from other substrates and end - products . </P>

Where does the cytric acid cycle take place