Citrate Oxidation in the Cytoplasmic Fraction of Rat Brain

Abstract

The cytoplasmic fraction derived from rat brain was shown to possess the ability to oxidize citrate in the presence of NADP, but not in that of NAD. The rate of citrate oxidation is limited by the rate of the aconitase-catalysed isomerization. The dependence of the reaction rate on the protein, citrate and NADP concentrations, and on reaction time, was determined. It was found that 2-oxoglutarate and NADPH, both formed in the citrate oxidation reaction, do not appear in amounts equivalent to the losses of citrate. The possible ways of utilization of the above products in the rat brain cytoplasmic fraction are discussed.It is suggested that the oxidation of citrate in rat brain cytoplasm may proceed-among other metabolic routes-through its conversion into isocitrate (aconitase) and then 2-oxoglutarate (NADP dehydrogenase) and oxaloacetate (aspartate aminotransferase). In addition it has been shown that hypoxia may markedly effect the activity of the cytoplasmic citrateoxidizing system.

β-Hydroxybutyrate in the Brain: One Molecule, Multiple Mechanisms

“…The steady-state concentration of citrate in the brain is one-fifth that of glucose and rarely exceeds 4 mmol/L in the cytosol (Patel, 1975). The increase in citrate levels due to ACLY inhibition is unlikely since citrate can also be oxidised in the cytosol by the aconitase reaction to form isocitrate and then 2-oxoglutarate and oxaloacetate (Gromek and Rafałowska, 1972). Citrate is also unlikely to enter the mitochondria for oxidation due to its high KM (4 mmol/L for entry into the inner mitochondrial space) (Patel, 1975).…”