Quantitative model of citrate production and secretion in prostate epithelial tissue

Healthy human prostate epithelial cells have the unique ability to produce and secrete large amounts of citrate into the lumen of the prostate. Citrate is a Krebs cycle metabolite produced in the condensation reaction between acetyl-CoA and oxaloacetate in the mitochondria of the cell. Using $^{13}$C-enriched substrates, the contributions of different metabolic pathways to this production and secretion of citrate could be identified. In this work we present a probabilistic model describing the production and secretion of citrate in the mitochondria of prostatic epithelial cells. We derived equations for the secretion probability of citrate and the contribution of pyruvate dehydrogenase complex (PDC) versus the anaplerotic pyruvate carboxylase (PC) pathways in supplying the Krebs cycle with carbons from pyruvate for the production of citrate. This measure is independent of initial $^{13}$C-enrichment of the administered supplements and of $^{13}$C J-coupling patterns, making this method robust also if SNR is low. We propose that these equations can be used to distinguish between citrate metabolism in healthy prostate tissue cells and in malignant cells, or they can be used to follow changes in citrate metabolism during the process towards malignancy.