Permeability of Rat White 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 malate^4–10. 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.