Permeability of rat adipose tissue mitochondria to citrate, isocitrate and 2-oxoglutarate.

Abstract

THE biosynthesis of fatty acids from glucose by white adipose tissue involves a multienzyme sequence: formation of pyruvate by glycolysis, oxidative decarboxylation of pyruvate in mitochondria, giving acetyl-CoA, and synthesis of fatty acids from acetyl-CoA outside the mitochondria. The biosynthesis thus requires the production of extramitochondrial acetyl-CoA from intramitochondrial acetyl-CoA. It is generally accepted that mitochondria are impermeable to acetyl-CoA and the pathway most favoured involves in turn formation of citrate from intramitochondrial acetyl-CoA by citrate synthase (EC 4.1.3.7), transfer of citrate across the mitochondrial membrane and the production of extramitochondrial acetyl-CoA from citrate by ATP citrate lyase (EC 4.1.3.6) (refs. 1–3). Isolated liver mitochondria have been shown to contain a vectorial transport system for citrate (and isocitrate) and a second system for 2-oxoglutarate both requiring catalytic amounts of phosphate and malate4–10. In view of the postulated key step of citrate transfer in the biosynthesis of fatty acids from glucose, it seemed important to establish clearly the presence of a citrate (and isocitrate) transport system in white adipose tissue mitochondria. The presence of a transport system for the transfer of 2-oxoglutarate has also been investigated.