The pioneering studies of Huggins, Mann, Williams-Ashman, Cooper, Farid, Grayhack, and a few others during the period of established that the prostate gland possessed unique metabolic activities associated with the specialized prostate function of production and secretion of enormously high levels of citrate. Moreover, the early studies also revealed that these metabolic activities were associated with the development and progression of prostate cancer (Pca). However, details of the pathways and mechanisms of regulation of intermediary metabolism were not established during that era. Over the past 30 years, with the exception of studies from our laboratory and from a few other isolated investigators, the area of prostate intermediary energy metabolism has been virtually ignored by the contemporary biomedical community. Today, in regard to intermediary energy metabolism, the prostate (particularly the prostate secretory epithelial cell) is still among the least studied and least understood tissues in the body.
The decades from 1945-1975 represent an era of major focus and intense research efforts in establishing the metabolic pathways typically associated with mammalian cells. Most of the metabolic relationships were derived from studies with liver, kidney, muscle, and other soft tissues. Unfortunately, the biochemists of that era had no interest in studying prostate cells, and the urologists had no interest in studying the intermediary metabolism of the prostate. The willingness to extrapolate the metabolic relationships demonstrated in other soft tissues to the prostate is not appropriate and leads to misrepresentations regarding prostate metabolism. Over 50 years ago, Huggins [1] noted that the human prostate uniquely exhibited a high rate of aerobic glycolysis and a low rate of respiration. Also, unlike essentially all other cells, citrate is an end-product of metabolism rather than an oxidizable intermediate. We have demonstrated that prostate epithelial cells have a uniquely limiting mitochondrial aconitase, which results in a truncated Krebs cycle. These and other unique metabolic rela-