Citrate is one of the major substrates for intracellular metabolism.
The extracellular level of citrate is stable in blood but varies locally, with slightly
increased levels in brain and high levels in prostate. Recent metabolomics research suggests that citrate level
is a potential harbinger of different pathophysiological states; its decrease has been correlated with male
infertility, brain diseases and metastatic cancer.
In this review we discuss the role of citrate as an energy substrate for sperm. We also review the function of
citrate released by astrocytes in the normal operation of neurons, and consequently we suggest a potential role
of neuronal plasma membrane citrate transporters in mental disorders. Finally, we review recent relevant
publications studying blood, urine and tissue citrate levels in cancer patients and hypothesize that extracellular
citrate supports cancer cell metabolism critical for metastasis.
Despite the importance of extracellular citrate in physiological and pathophysiological processes, surprisingly
little is known about citrate synthesis in specialized cells, or about citrate transporters controlling citrate
movement across various membranes. Determination of the molecular origin of citrate transporters in
astrocytes, sperm and cancer cells could offer novel therapeutic targets and the possibility to
pharmacologically regulate citrate release and uptake for preventing male infertility, treating mental diseases
and targeting cancer.